Source: AGRICOLA database (1970-1996)

Ernst, E. and C. Stevinson (1999). New data on old herbal remedies. Perfusion . May 12(5): 192-194.

Herbal remedies are booming worldwide, This article briefly reviews our present knowledge regarding three of the most popular herbal drugs: echinacea, ginkgo biloba and hypericum. With all three, several open questions persist. It is concluded that herbal treatments can represent promising therapeutic options worthy of more research, particularly randomized clinical trials and systematic reviews.

Chung, H. S., A. Harris, et al. (1999). Ginkgo biloba extract increases ocular blood flow velocity. Journal Of Ocular Pharmacology And Therapeutics. Jun 15(3): 233-240.

We evaluated a possible therapeutic effect of Ginkgo biloba extract (GEE) on glaucoma patients that may benefit from improvements in ocular blood flow. A Phase I cross-over trial of GEE with placebo control in 11 healthy volunteers (8 women, 3 men: Age; 34 +/- 3 years, mean +/- SE) was performed. Patients were treated with either GEE 40 mg or placebo three times daily orally, for 2 days. Color Doppler imaging (Siemens Quantum 2000) was used to measure ocular blood flow before and after treatment. There was a two week washout period between GEE and placebo treatment.Ginkgo biloba extract significantly increased end diastolic velocity (EDV) in the ophthalmic artery (OA) (baseline vs GEE-treatment; 6.5 +/- 0.5 vs 7.7 +/- 0.5 cm/sec, 23% change, p=0.023), with no change seen in placebo (baseline vs GEE-treatment; 7.2 +/- 0.6 vs 7.1 +/- 0.5 cm/sec, 3 % change, p=0.892). No side effects related to GEE were found. Ginkgo biloba extract did not alter arterial blood pressure, heart rate, or IOP.Ginkgo biloba extract significantly increased EDV in the OA and deserves further investigation in ocular blood flow and neuroprotection for possible application to the treatment of glaucomatous optic neuropathy as well as other ischemic ocular diseases.

Ellnain, W. M. and G. Zgorka (1999). High-performance liquid chromatography and thin-layer chromatography of phenolic acids from Ginkgo biloba L-leaves collected within vegetative period. Journal Of Liquid Chromatography And Related Technologies 22(10): 1457-1471.

In this paper, thin-layer chromatography and highperformance liquid chromatography for the qualitative and quantitative analysis of phenolic acids in Ginkgo biloba L. leaves are described. The amounts of both free and bound phenolic acids were determined within the whole vegetative period. For this purpose, a special extraction procedure, comprising acid and alkaline hydrolyses, was used. The described method allowed us to identify and estimate the concentration levels of eight phenolic acids: protocatechuic, para-hydroxybenzoic, vanillic, caffeic, isovanillic, para-coumaric, ferulic, and sinapic.Depending on the part of the plant vegetation, significant differences in the content of the compounds examined were observed and discussed. The elaborated method could be used in studies on the seasonal distribution of phenolic acids in plant material.

Kimura, Y., S. Matsuo, et al. (1999). A new affinity chromatography using yeast invertase-sepharose 4B for purification of plant endo-beta-N-acetylglucosaminidases. Bioscience Biotechnology And Biochemistry. May 63(5): 948-950.

For the purification of plant endo-beta-N-acetylglucosaminidase, in this report, we introduce a new affinity chromatography using the reduced and carboxymethylated yeast invertase (cm-YI) as a ligand. Two plant endo-8-N-acetylglucosaminidases (endo-LE from tomato fruits (Kimura, Y., et al. Biochim. Biophys. Acta 1381, 27-36 (1998)) and endo-GB from Ginkgo biloba seeds (Kimura, Y,, et al, Biosci. Biotechnol, Biochem., 62, 253-261 (1998)) could completely bind to the high-mannose type N-glycans linked to the immobilized yeast invertase and the activities of both enzymes could be recovered by increasing the concentration of NaCl, By using this purification procedure with some other purification procedures, endo-LE could be purified 1,700-fold and endo-GB was purified to apparent homogeneity at 63 kDa as reported previously.

Janssens, D., J. Remacle, et al. (1999). Protection of mitochondrial respiration activity by bilobalide. Biochemical Pharmacology. Jul 58(1): 109-119.

Mitochondria alteration is an early event in ischemia-induced damage, and its prevention improves tissue survival upon reperfusion. Adenine translocase and complex I activities are rapidly affected by ischemia. Ginkgo biloba extract demonstrates anti-ischemic properties attributable to the terpenoid fraction, mainly due to the presence of bilobalide. The mechanism of the protection afforded by bilobalide is not yet known. In this work, the effects of bilobalide on mitochondrial respiration were investigated. Mitochondria isolated from rats treated with bilobalide (2 to 8 mg/kg) showed a dose-dependent increase in the respiratory control ratio, due to a lower oxygen consumption during state 4. Bilobalide also decreased the sensitivity of oxygen consumption to inhibition of complex I by Amytal or to inhibition of complex III by antimycin A or myxothiazol. There was no protection of complexes IV and V. It also increased the activity of complex I but not of adenine translocase. Similar effects were also obtained in vitro when control mitochondria were preincubated for 1 hr with 0.8 mu g/mL bilobalide. Treatment of the rats with 8 mg/kg bilobalide also prevented the ischemia-induced decrease in state 3 of the mitochondrial respiration and thus the decrease in RCR. The protective effect of bilobalide on cellular ATP content observed under ischemic conditions can be correlated with the above observations. By protecting complex I and III activities, bilobalide allows mitochondria to maintain their respiratory activity under ischemic conditions as long as some oxygen is present, thus delaying the onset of ischemia-induced damage. This mechanism provides a possible explanation for the anti ischemic properties of bilobalide and of Ginkgo biloba extract in therapeutic interventions. BIOCHEM PHARMACOL 58;1: 109-119, 1999. (C) 1999 Elsevier Science Inc.

Pryse, P. W. (1999). Do we have drugs for dementia? No. Archives Of Neurology. Jun 56(6): 735-737.

Tateyama, S., R. Wititsuwannakul, et al. (1999). Dolichols of rubber plant, ginkgo and pine. Phytochemistry . May 51(1): 11-15.

Using a two-plate thin-layer chromatography method, we analyzed polyisoprenoid alcohols (dolichols and polyprenols) of the rubber plant Hevea brasiliensis (angiosperm), and of ginkgo Ginkgo biloba and pine Pinus sylvestris (gymnosperms). Special attention was paid to the occurrence of dolichol in various tissues of different plants. Dolichols were found to occur in all of the tissues examined except for flowers of the rubber plant. The chain length distributions of dolichols in seeds,young roots, young shoots, young leaves and old leaves of the rubber plant were C-70-C-95, C-85-C-105, C-80-C-105, C-75-C-105 and C-65-C-90, respectively. In the case of ginkgo, the chain length distributions of dolichols in seeds, embryos, young and old leaves were C-70-C-90, C-70-C-85, C-70-C-90 and C-80-C-95, respectively. Pine seeds were found to contain dolichols with the chain length distribution of C-70-C-90. Two kinds of polyprenol families were detected in leaves of the rubber plant and ginkgo. The longer chain polyprenol family was also detected in seeds of the rubber plant, in seeds and embryos of ginkgo and in seeds of pine. The chain length distributions of the polyprenols were not necessarily the same as those of dolichols occurring in the same tissues. (C) 1999 Elsevier Science Ltd. All rights reserved.

Xu, J. P., Y. C. Rui, et al. (1999). Antagonistic effects of Ginkgo biloba extract on adhesion of monocytes and neutrophils to cultured cerebral microvascular endothelial cells. Acta Pharmacologica Sinica. May 20(5): 423-425.

AIM: To study the action of Ginkgo biloba extract (GbE) on tumor necrosis factor (TNF-alpha)-induced adhesion of monocytes (Mon) and neutrophils (Neu) to cultured cerebral microvascular endothelial cells. METHODS: TNF-alpha-induced endothelial adhesivity toward Mon and Neu was studied using bovine cerebral microvascular endothelial cells (BCMEC) in vitro. The number of Mon and Neu adhering to the BCMEC monolayers was determined by flow cytometry. RESULTS: Pretreatment of BCMEC with TNF-alpha increased Mon and Neu adhesion to BCMEC from 12.5% +/- 0.2% to 31.3% +/- 0.5% and from 13.8% +/- 0.4% to 32.1% +/- 0.5%, respectively. GbE (1-100 mg.L-1) inhibited the effect of TNF-alpha in a concentration-dependent manner. E-selectin mAb (1 mg.L-1) blocked Mon and Neu adhesion to BCMEC induced by TNF-alpha. CONCLUSION: The inhibition of GbE on Mon and Neu adhesion to BCMEC was mediated through the suppression of E-selection expression.

Gajewski, A. and S. A. Hensch (1999). Ginkgo biloba and memory for a maze. Psychological Reports. Apr 84(2): 481-484.

A number of sources suggest that the natural herb ginkgo biloba enhances mental sharpness by increasing blood now to the brain. A preliminary study was designed to examine whether memory for a maze would be enhanced in 5 mice who received a dietary supplement containing ginkgo biloba. The mice showed an improved memory for the maze as evidenced by a decrease in the number of errors in reaching the goal box when they received gingko biloba as a dietary supplement.

Carrier, D. J., B. T. A. van, et al. (1999). Distribution of ginkgolides and terpenoid biosynthetic activity in Gingko biloba (vol 48, pg 89, 1998). Phytochemistry . Apr 50(8).

Chang, J. (1999). Scientific evaluation of traditional Chinese medicine under DSHEA: A conundrum. Journal Of Alternative And Complementary Medicine. Apr 5(2): 181-189.

In the United States, traditional Chinese medicines (TCM) are currently sold as dietary supplements, as defined by The Dietary Supplement Health and Education Act (DSHEA). This legislation is unique to the United States and while "structure and function" claims are allowable under DSHEA, disease claims are not. The narrow definition, however, poses a challenge to designing appropriate clinical studies that can provide data for "structure and function" claim substantiation. The process of melding Chinese herbal medicines into the dietary supplement category is complex and there is a need to define a clinical trial paradigm carefully that addresses "structure and function claims" without sacrificing scientific rigor. It is frequently not recognized that TCM favors an amalgamation of several herbs to generate the putative clinical effect. Because of this historical multiherb approach, the reliance on retrospective data to support the potential health benefits of an herb extract has severe limitations. Notwithstanding the immense value of identifying the pharmacological activity of a TCM herb to a chemical suitable for pharmaceutical development, another approach to safe and efficacious herbal products is to develop a standardized herbal extract. This article highlights issues related to the latter approach and will discuss a research-based strategy that may be suitable for validating, in part, the putative health benefits of TCM.

Ranchon, I., J. M. Gorrand, et al. (1999). Functional protection of photoreceptors from light-induced damage by dimethylthiourea and Ginkgo biloba extract. Investigative Ophthalmology And Visual Science. May 40(6): 1191-1199.

PURPOSE. To investigate the functional protective effect of a synthetic (dimethylthiourea, DMTU) and a natural antioxidant (Ginkgo biloba extract, EGb 761) against light-induced retinal degeneration.METHODS. Wistar rats were exposed for 24 hours to 1700-lux light after treatment with DMTU or EGb 761. Electroretinograms were recorded before and on day (D)1, D3, D8, D15, D22, and D29 after light exposure. The b-wave amplitude was plotted against log L (ganzfeld luminance), providing the b-wave sensitivity curve. The Naka-Rushton function fitted to the sensitivity curve enabled derivation of the parameters B-max (saturated amplitude) and K (luminance-inducing B-max/2). In addition, rats from each group were killed for retinal morphometric analyses.RESULTS. In the untreated group, light exposure caused collapse of the b-wave sensitivity curves. B-max was reduced by 51% at DI without subsequent recovery. K increased temporarily, reverting to normal Values 8 days later. The outer nuclear layer thicknesses decreased markedly in the superior retina. In the treated groups, light exposure had a weaker effect on sensitivity curves. The values of B-max were not significantly different from those in the unexposed-untreated group, although K increased temporarily. Retinal morphometry was preserved.CONCLUSIONS. Dimethylthiourea and EGb 761 afford functional protection against Light-induced retinal damage.

Wolff, R. L., F. Pedrono, et al. (1999). The seed fatty acid composition and the distribution of Delta 5-olefinic acids in the triacylglycerols of some Taxares (Cephalotaxus and Podocarpus). Journal Of The American Oil Chemists Society. Apr 76(4): 469-473.

The fatty acid compositions of the seeds from four Cephalotaxus species or varieties (plum yews; Cephalotaxaceae) and two Podocarpus species (podocarps; Podocarpaceae) have been established. These compositions were compared with those previously published for some Taxaceae species (Taxus and Torreya). Cephalotaxaceae; Podocarpaceae, and Taxaceae belong to the Taxares suborder. Delta 5-Olefinic acids are present in the seed lipids from all species analyzed. In Cephalotaxus, Podocarpus, and Torreya, the prominent Delta 5-olefinic acid that occurs is the trienoic acid 5,11,14-20:3 (sciadonic) acid, comprising from 6.7 to 26.4% of total fatty acids. In these species, the Delta 5,11 structure is largely favored over the Delta 5,9 structure: the 5,9-18:2 (taxoleic) and 5,9,12-18:3 (pinolenic) acids are at the limit of detection, in contrast to Taxus and most Pinaceae species, where these two Delta 5-olefinic acids generally predominate. 14-Methylhexadecanoic acid, an habitual though minor component of Pinaceae and Ginkgo biloba seed lipids, could not be detected in Cephalotaxus species studied here and was tentatively identified in trace amounts only in one Podocarpus species. In addition to sciadonic acid, Cephalotaxus and Podocarpus seeds are characterized by unusually high amounts of 11,14-20:2 acid, in the range of 3.1-12.0%. This contrasts with most of the 170 species of conifers analyzed so far (from the families Pinaceae, Cupressaceae, Taxodiaceae, Taxaceae, and Sciadopityaceae, which belong to the Pinares suborder), where this acid is generally less than or equal to 2%. A close resemblance between Torreya grandis and three of the Cephalotaxus species analyzed might be indicative of some phyletic relationship between the families Cephalotaxaceae and Taxaceae. C-13 nuclear magnetic resonance spectroscopy of the seed oils from C. drupaceae and P. andinus has shown that Delta 5-olefinic acids are apparently excluded from the internal position of triacylglycerols, which is a characteristic common to all Coniferales species analyzed so far, and consequently of great antiquity.

Fitzl, G., R. Martin, et al. (1999). Protective effects of Ginkgo biloba extract EGb 761 on myocardium of experimentally diabetic rats - I: Ultrastructural and biochemical investigation on cardiomyocytes. Experimental And Toxicologic Pathology. May 51(3): 189-198.

Chronic diabetes in man and animal models develops cardiomyopathic alterations which cannot be absolutely avoided by insuline therapy. Since diabetic damage is part ly attributed to oxidative stress antioxidative treatment could be able to reduce the alterations. Aim of this study was to investigate the cardioprotective effects of EGb 761, Known as a radical scavenger, against diabetic alterations in rats.The diabetes was induced by i.p. injection of 60 mg/kg body weight streptozotocin. Duration of diabetes was 4 months, the protected group received 100 mg/kg body weight EGb 761 with the drinking water over 3 months.Electron and light microscopic morphometry of left-ventricular samples revealed typical diabetic alterations consisting in decrease of volume fraction of myofibrils, SR and t-tubules and diminishing of cardiomyocyte diameter, increase of interstitial volume, mitochondrial size and volume fraction, and of vacuoles and of lipid drops. EGb treat ment could gradually prevent the loss of myofibrils and reduction of myocyte diameter but has only little influence on interstitial and mitochondria volume. The diabetic-induced increase of lipid and vacuoles and the decrease of SR and t-tubules were not influenced.Biochemical parameters of oxidative stress: malondialdehyde (MDA) was only insignificantly altered by diabetes and EGb. The superoxide dismutase (SOD) activity was in creased by diabetes and more increased by EGb treatment. Creatine kinase (CK) activity was diminished by diabetes but slightly increased by EGb. The polymerase chain reaction (PCR) of i-NOS was not different between the diabetic and protected diabetic groups.

Welt, K., J. Weiss, et al. (1999). Protective effects of Ginkgo biloba extract EGb 761 on the myocardium of experimentally diabetic rats - II. Ultrastructural and immunohistochemical investigation on microvessels and interstitium. Experimental And Toxicologic Pathology. May 51(3): 213-222.

Interstitial and microvascular disorders are known as a characteristic part of the diabetic cardiomyopathy and to resist partly insulin therapy. Aim of this study was to demonstrate structure-protecting effects of Ginkgo Extract EGb 761 known as a natural radical scavenger in streptozotocin-diabetic rats on the microvascular compartment.Wistar rats (n = 5) were made diabetical by i.p. injection of 60 mg/kg body mass streptozotocin for 4 months. Rats of the protected group (n = 5) received daily 100 mg/kg body mass EGb 761 for 3 months, starting 1 month after induction of diabetes. 5 age-matched rats served as control.The volume fraction of interstitium was slightly but significantly increased only in the unprotected diabetic group. Diminishing of the capillary to the myocyte ratio was seen in the diabetic but not in the protected group.Immunostaining of collagen revealed a slight increase of type Ill, type IV, and type VI fibres in the interstitium, more expressed in the unprotected group. Ultrastuctural morphometry revealed significant thickening of endothelial and muscular basement membranes in diabetic animals, less expressed in the EGb- protected group. The capillary diameter was slightly increased in the diabetic and slightly decreased in the protected group. The number of plasmalemmal vesicles was tendentially more decreased, that of lysosomes more increased in the diabetic than in the protected group.It is concluded that EGb 761 can diminish partly interstitial fibrosis and reduce endothelial and muscular basement membrane thickening of the diabetic myocardium. It may contribute to prevent late diabetic complications.

Ernst, E. and M. H. Pittler (1999). Ginkgo biloba for dementia - A systematic review of double-blind, placebo-controlled trials. Clinical Drug Investigation. Apr 17(4): 301-308.

Objective: To systematically review the clinical evidence of Ginkgo biloba preparations as a symptomatic treatment for dementia.Methods: Computerised literature searches were performed to identify all double-blind, randomised, placebo-controlled trials assessing clinical end-points of Ginkgo biloba extract as a treatment for dementia. Databases included Medline, Embase, Biosis and the Cochrane Library. There were no restrictions regarding the language of publication. Data were extracted in a standardised, predefined fashion, independently by both authors.Results: Nine double-blind, randomised, placebo-controlled trials met the inclusion criteria and were reviewed. These studies are of varying methodological quality. They collectively suggest that Ginkgo biloba extract is more effective for dementia than placebo. However, a number of caveats pertain. Few, generally mild, adverse effects were reported.Conclusion: These findings are encouraging and warrant independent, large scale confirmatory and comparative trials.

Tommasi, F., C. Paciolla, et al. (1999). The ascorbate system in recalcitrant and orthodox seeds. Physiologia Plantarum. Feb 105(2): 193-198.

Recalcitrant seeds of Ginkgo biloba L,, Quercus cer I is L,, Aesculus hippocastanum L, and Cycas revoluta Thunb, are shed bgl the plant at a high moisture content, contain a large amount of ascorbic acid (ASA) and maintain high ascorbate (ASC) peroxidase (EC 1.11.1.11) activity. Three proteins showing ASC peroxidase activity are present in G, biloba seeds. Conversely, dry orthodox seeds (Vicia faba L,, Avena sativa L,, Pinus pinea L.) are completely devoid of ASA and ASC peroxidase. Experimentally induced rapid variations of the mater Iel el in both recalcitrant and orthodox seeds do not affect the ASC peroxidase; slow dehydration affects the ASC peroxidase activity moderately in recalcitrant seeds, but provokes a complete loss of germinability. Another peculiar difference between orthodox and recalcitrant seeds concerns the ascorbate recycling enzymes, ascorbate free radical (AFR) reductase (EC 1.6.5.4) and dehydroascorbate (DHA) reductase (EC 1.8.5.1), The DHA reduction capability is lo in recalcitrant seeds, but is high in the orthodox ones. In contrast, AFR reductase activity is high in recalcitrant seeds and low in the orthodox ones. Data reported here concerning the ASC system appear to contribute to better understanding the recalcitrance. The presence of three different proteins showing ASC peroxidase activity in the archaic seed-bearing plant G. biloba and its involvement in the spermatophyte evolution is discussed.

Ott, B. R. and N. J. Owens (1998). Complementary and alternative medicines for Alzheimer's disease. Journal Of Geriatric Psychiatry And Neurology. Win 11(4): 163-173.

The recent successes of large, multicenter clinical trials of acetylcholinesterase inhibitors for symptomatic treatment of Alzheimer's disease have spawned enthusiasm that this common and fatal neurologic disease is "treatable." A parallel explosion has occurred in the consumption of alternative medicines by the public seeking more effective, natural, or safer methods for treatment of dementia. Some of these medicines may, in fact, be biologically active in modulating the disease as well as producing side effects and interactions with accepted pharmaceuticals. This review brings to focus the scientific evidence presently available regarding such agents.

Kimura, Y., T. Harada, et al. (1999). Purification and some chemical properties of 30 kDa Ginkgo biloba glycoprotein, which reacts with antiserum against beta 1 -> 2 xylose-containing N-glycans. Bioscience Biotechnology And Biochemistry. Mar 63(3): 463-467.

From the seeds of Ginkgo biloba, a glycoprotein, which is a major component that reacts with an antiserum against beta 1-->2 xylose-containing N-glycans, has been purified and characterized, The N-terminal amino acid sequence of the purified glycoprotein was H-K-A-N-X-V-T-V-A-F-V-M-T-Q-H-L-L-F-G-Q-. The molecular mass was estimated to be 17 kDa and 16 kDa by SDS-PAGE under reducing conditions, however, the molecular mass of this glycoprotein in the native state was 30,762 by MALDI-TOF MS, suggesting that this glycoprotein consists of two subunits; one is glycosylated and the other is not. The structure of N-glycan linked to this glycoprotein (designated 30 kDa GBGP) was identified as Man(3)Fuc(1)Xyl(1)GlcNAc(2), which is the predominant N-glycan linked to the storage glycoproteins in the same seeds (Kimura, Y et al, (1998) Biosci. Biotechnol, Biochem, 62, 253-261). From the peptic digest of the carboxymethylated glycosylated subunit, one glycopeptide was purified by RP-HPLC and the amino acid sequence was identified as H-K-A-N-N(Man(3)Fuc(1)Xyl(1)GlcNAc(2))-V-T-Y-A-F, which corresponded to the N-terminal amino acid sequence.

Biber, A. and E. Koch (1999). Bioavailability of ginkgolides and bilobalide from extracts of Ginkgo biloba using GC/MS. Planta Medica. Mar 65(2): 192-193.

The bioavailability of ginkgolides A, B and bilobalide was studied in rats after single oral administration of 30, 55 and 100 mg/kg Ginkgo extract EGb 761(R). The plasma levels of the terpene lactones were measured by a specific GC/MS method. The pharmacokinetics of the mentioned substances were found to be dose-linear. For the lowest dose maximum concentrations were 68, 40 and 159 ng/ml and half-lives 1.7, 2.0 and 2.2 h for ginkgolide A, B and bilobalide, respectively, Clearance values ranged from 24.2 to 37.6 ml/min/kg.

Chen, C., T. T. Wei, et al. (1999). Different effects of the constituents of EGb761 on apoptosis in rat cerebellar granule cells induced by hydroxyl radicals. Biochemistry And Molecular Biology International. Mar 47(3): 397-405.

The present study was conducted to evaluate the different effects of the constituents of EGb761(Ginkgo biloba Extract) on apoptosis in cerebellar granule cells induced by hydroxyl radicals. The total flavonoid component of EGb761, two pure EGb761 components (rutin and quercetin), and a mixture of flavonoids and terpenes protected cerebellar granule cells from oxidative damage and apoptosis induced by hydroxyl radicals. ESR(electron spin resonance) results showed that the IC,, of the flavonoids for scavenging hydroxyl radicals was almost the same as that of EGb761, even though flavonoids make up only 24% of EGb761, implying that other constituents of EGb761 besides flavonoids can scavenge hydroxyl radicals. Total terpenes of EGb761 did not protect against apoptosis. Flavonoids and terpenes did not show a synergistic effect in this regard. Terpenes did not scavenge hydroxyl radicals directly, which might be related to their "cage-like" structures.

Wu, L. S. H., G. H. H. Hong, et al. (1999). Classification of the single oleosin isoform and characterization of seed oil bodies in gymnosperms. Plant And Cell Physiology. Mar 40(3): 326-334.

Oleosins are hydrophobic proteins abundantly present in the oil bodies of plant seeds. Two immunologically distinct oleosins are present in seed oil bodies of diverse angiosperms, and classified as high and low M-r isoforms according to their relative molecular masses in each species. Only one putative oleosin was found in seed oil bodies of three representative gymnosperm species, Pinus kouaiensis, Ginkgo biloba, and Cycas revoluta. The three gymnosperm oleosins were restricted to oil bodies, as detected on immune-assaying. Immunological cross-recognition using antibodies against the three putative gymnosperm oleosins and those against the two (high and low M-r) rice oleosin isoforms suggests that the single oleosin of pine or ginkgo is immunologically related to the low M-r isoform of angiosperms, while the single cycad oleosin is immunologically distinct from both low and high M-r isoforms of angiosperms. Oil bodies were found in embryos and megagametophytes of these three species, as observed on electron microscopy. Seed oil bodies purified from these three gymnosperms maintained their integrity via electronegative repulsion and steric hindrance on the surface of the organelles. The compositions of the three essential constituents (neutral lipid, phospholipid and protein) in seed oil bodies from these three species were determined and compared with those calculated from the oil body model proposed in angiosperms, The results suggested that seed oil bodies of gymnosperms and angiosperms possess similar surface properties and structural organization.

Pierre, S., I. Jamme, et al. (1999). Ginkgo biloba extract (EGb 761) protects Na,K-ATPase activity during cerebral ischemia in mice. Neuroreport . Jan 10(1): 47-51.

NEUROPROTECTIVE drugs such as Ginkgo biloba extract (EGb 761) could prevent the ischemia-induced impairment of the Na,K-ATPase activity. In this study, Na,K-ATPase activity and expression, contents in fatty acids and malondialdehyde, an index of lipoperoxidation, were compared in the ipsilateral (ischemic) and the contralateral (unlesioned) cortices after Ih of unilateral focal cortices cerebral ischemia in the mouse. EGb 761 (100 mg/kg) was administered daily to half of the animals for 10 days before ischemia. Ischemia significantly reduced Na,K-ATPase activity by about 40% and increased malondialdehyde content; EGb 761 pretreatment abolished these effects. The free radical scavenger properties of EGb 761 are a potential mechanism by which Na,K-ATPase injury and lipoperoxidation are prevented. (C) 1999 Lippincott Williams and Wilkins.

Kim, G. H., S. M. Kang, et al. (1999). Laboratory evaluation of selected anti-stain chemicals for control of fungal staining on Ginkgo sapwood. Forest Products Journal. Mar 49(3): 49-52.

The susceptibility of Ginkgo sapwood to fungal attack and the ability of selected anti-stain chemicals to control colonization of sapstain and mold fungi on green Ginkgo sapwood were evaluated. Ginkgo sapwood was very susceptible to fungal staining, suggesting that prompt application of anti-stain chemicals after sawing will be essential for preventing fungal colonization. The ability of eight chemicals to prevent fungal discoloration of Ginkgo sapwood was evaluated using a small-scale laboratory procedure. NexGen provided excellent protection against stain and mold. NP-1 Plus, PQ-8, and Busan 1030 provided good short-term protection (4 wk), but higher chemical loadings were required for long-term protection (6 wk.). Britewood Q, Britewood S, Britewood XL, and Nytek-GD provided little or no protection over the test period.

Lugasi, A., P. Horvahovich, et al. (1999). Additional information to the in vitro antioxidant activity of Ginkgo biloba L. Phytotherapy Research. Mar 13(2): 160-162.

The in vitro antioxidant and free radical scavenging activity of the ethanol extract from Ginkgo biloba L. was examined in different systems. The extract showed hydrogen-donating ability, reducing power, copper-binding property, free radical scavenging activity in a H2O2/. OH-luminol system and it could prevent the autoxidation of linoleic acid. All these properties are involved in the overall antioxidant activity of Ginkgo biloba which makes it suitable for the prevention of human disease in which free radicals play an important role. Copyright (C) 1999 John Wiley and Sons, Ltd.

Wolff, R. L., W. W. Christie, et al. (1999). Reinvestigation of the polymethylene-interrupted 18 : 2 and 20 : 2 acids of Ginkgo biloba seed lipids. Journal Of The American Oil Chemists Society. Feb 76(2): 273-276.

The fatty acid composition of Ginkgo biloba seed lipids was reinvestigated with particular emphasis on the polymethylene-interrupted octadecadienoic and eicosadienoic acids. Analysis of the picolinyl esters and 4,4-dimethyloxazoline derivatives by capillary gas-liquid chromatography on a highly polar cyanopropyl polysiloxane stationary phase coupled with mass spectrometry revealed the presence of three such acids, with the structures 5,9-18:2, 5,11-18:2, and 5,11-20:2. This indicated that in G. biloba seeds, cis-vaccenic (11-18:1) acid may be a substrate for the Delta 5-desaturase characteristic of gymnosperms. The 5,11-18:2 acid was not limited to G. biloba, as it may occur in a few other species. The 5,11-20:2 acid is a common component of the seed lipids from almost all gymnosperm species analyzed so far.

Cupp, M. J. (1999). Herbal remedies: Adverse effects and drug interactions. American Family Physician. Mar 59(5): 1239-1244.

A growing number of Americans are using herbal products for preventive and therapeutic purposes. The manufacturers of these products are not required to submit proof of safety and efficacy to the U.S. Food and Drug Administration before marketing. For this reason, the adverse effects and drug interactions associated with herbal remedies are largely unknown. Ginkgo biloba extract, advertised as improving cognitive functioning, has been reported to cause spontaneous bleeding, and it may interact with anticoagulants and antiplatelet agents. St. John's wort, promoted as a treatment for depression, may have monoamine oxidase-inhibiting effects or may cause increased levels of serotonin, dopamine and norepinephrine. Although St. John's wort probably does not interact with foods that contain tyramine, it should not be used with prescription antidepressants. Ephedrine-containing herbal products have been associated with adverse cardiovascular events, seizures and even death. Ginseng, widely used for its purported physical and mental effects, is generally well tolerated, but it has been implicated as a cause of decreased response to warfarin. Physicians must be alert for adverse effects and drug interactions associated with herbal remedies, and they should ask all patients about the use of these products.

Punkt, K., I. Psinia, et al. (1999). Effects on skeletal muscle fibres of diabetes and Ginkgo biloba extract treatment. Acta Histochemica. Feb 101(1): 53-69.

Combined cytophotometric and morphometric analysis of muscle fibre properties and myosin heavy chain electrophoresis were performed on extensor digitorum longus and soleus muscles from healthy rats and rats with streptozotocin-induced diabetes. Moreover, the protective effect of Ginkgo biloba extract, a potent oxygen radical scavenger, on diabetic muscles was investigated. Changes in fibre type-related enzyme activities, fibre type distribution, fibre cross areas and myosin isoforms were found. In muscles of diabetic rats, a metabolic shift was measured mainly in fibres with oxidative metabolism. Fast-oxidative glycolytic fibres showed a shift to more glycolytic metabolism and about a third transformed into fast-glycolytic fibres. Slow-oxidative fibres became more oxidative. Fibre atrophy was measured in diabetic muscles dependent on fibre type and muscle. Different fibre types atrophied to a different degree. Therefore, a decreased area percentage of slow fibres and an increased area percentage of fast fibres of the whole muscle cross section in both muscles were found. This is supported by reduced slow and increased fast myosin heavy chain isoforms. These alterations of diabetic muscle fibres could be due to less motion of diabetic rats and diabetic neuropathy. After treatment with Ginkgo biloba extract, enzyme activities were increased mainly in oxidative fibres of diabetic muscles, which was interpreted as protective effect. Generally, the soleus muscle with predominant oxidative metabolism was more vulnerable to diabetic alterations and Ginkgo biloba extract treatment than the extensor digitorum longus muscle with predominant glycolytic metabolism.

Chen, F., S. Yasuda, et al. (1999). Evidence for a novel biosynthetic pathway that regulates the ratio of syringyl to guaiacyl residues in lignin in the differentiating xylem of Magnolia kobus DC. Planta . Feb 207(4): 597-603.

The biosynthetic pathways to monolignols in Magnolia kobus were investigated by feeding stems with a deuterium-labeled precursor. Pentadeutero [gamma,gamma-H-2(2), (OCH3)-H-2] coniferyl alcohol was supplied to shoots of Magnolia kobus and the incorporation of the labeled precursor into lignin was traced by gas chromatography-mass spectrometry. In addition to the direct incorporation of the labeled precursor into guaiacyl units, we detected a significant amount of pentadeuterium-labeled syringyl units with two gamma-deuterium atoms. The relative level of trideuterium-labeled syringyl monomers (the result of conversion via the cinnamic acid pathway, in which two gamma-deuterium atoms are removed during enzymatic re-oxidation) was negligible. Our results provide conclusive evidence for a novel alternative pathway for generation of lignin subunits at the monolignol stage and they suggest that this new pathway might be important for regulation of the composition of lignin.

Maurer, K., R. Ihl, et al. (1998). Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type. Phytomedicine . Dec 5(6): 417-424.

Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo biloba special extract EGb 761 (Tebonin(R) forte, manufactured by Dr. Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size.

Brautigam, M. R. H., F. A. Blommaert, et al. (1998). Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double blind placebo-controlled study. Phytomedicine . Dec 5(6): 425-434.

A growing number of people is subject to age-related cognitive impairment due to the proportional increase of the ageing population. Therefore, there is a growing interest in cognition-enhancing substances. The efficacy of an alcohol/water extract of Ginkgo biloba in elderly individuals with memory- and/or concentration complaints was tested in a randomized, double-blind, placebo-controlled study by using both subjective and objective parameters.After a wash-out period of 4 weeks 241 non-institutionalised patients in the age range 55-86 years were randomly allocated to receive either Ginkgo biloba alcohol/water extract in a high dose (HD), a low dose (LD) or a placebo (PL) for 24 weeks. Patients were assessed using a psychometric testbattery in the following order: Expended Mental Control Test (EMCT) measuring attention and concentration, Benton Test of Visual Retention-Revised (measures short term visual memory), Rey Test part 1 (measures short term memory and learning curve), Beck Depressive Inventory (BDI) measuring the presence and severeness of a depression in order to exclude depressive patients and Rey Test part 2 (measures long term memory: recognition). Furthermore, subjective perception of memory and concentration was measured. 197 patients completed the study (mean MMSE score: 26.29).In the subjective test, the EMCT, the Rey 1 and Rey 2 no significant differences in improvement in time between the groups were observed. In the Benton test increases of 18%, 26% and 11% (expressed as percentage of baseline scores) were observed in the HD, LD and PL respectively (MANOVA; p = 0.0076). No substantial correlation was observed between subjective perception of the severeness of memory complaints and the objective test results. No differences in the number of (gastrointestinal) side effects were observed between placebo and verum groups.These results indicate that the use of Ginkgo extracts in elderly individuals with cognitive impairment might be promising. Further research using both subjective and objective measurements is recommended.

Schulz, H., M. Jobert, et al. (1998). The quantitative EEG as a screening instrument to identify sedative effects of single doses of plant extracts in comparison with diazepam. Phytomedicine . Dec 5(6): 449-458.

Two multiple crossover studies, each involving 12 adult female subjects, were performed to screen for acute sedative effects of eight different plant extracts (Valeriana off., Lavandula off., Passiflora incarnata, Kava-kava, Melissa off., Eschscholzia californica, Hypericum perforatum and Ginkgo biloba). Both studies were placebo-controlled, and a single dose of 10 mg diazepam was used as an active reference drug. All drugs were administered as a single dose. Prior to administration, as well as 2 h and 3 h after administration the EEG was recorded from two leads (F-z-C-z and O-z-T-6) under vigilance-controlled and resting conditions, for five minutes each. The extend of tiredness was rated by the subjects on a visual analogue scale. The EEG was digitized and stored for later analysis of the absolute and relative power of seven factorially defined frequency bands.Under diazepam the power in the theta frequency band decreased while it increased in the beta band. In contrast, some plant extracts showed an increase of power in the theta frequency band, but no increase in the beta frequency range. Valerian extract, which was administered in both studies, displayed an increase of power in the delta and theta band and a decrease in the beta band. Self-rated tiredness increased under diazepam and under some of the plant extracts but not with placebo. The results show that sedating effects of plant extracts can be identified by quantitative EEG analysis and by self-assessment instruments.

Kozubek, A. and J. H. P. Tyman (1999). Resorcinolic lipids, the natural non-isoprenoid phenolic amphiphiles and their biological activity. Chemical Reviews. Jan 99(1): 1-25.

Landsberg, G. (1999). Identification and medical management of cognitive dysfunction syndrome and other geriatric behavior problems. Veterinary Medicine. Feb: 2-19.

Winter, J. C. and D. Timineri (1999). The discriminative stimulus properties of EGb 761, an extract of Ginkgo biloba. Pharmacology Biochemistry And Behavior. Mar 62(3): 543-547.

Stimulus control was established in a group of nine rats using a dose of EGb 761 of 10 mg/kg, administered IF, 15 min before training. A two-lever operant task using a fixed-ratio 10 schedule of sweetened milk reinforcement was used. Based upon a criterion for the presence of stimulus control of five consecutive sessions during which 83% or more of all responses were on the appropriate lever, a mean of 24 sessions was required to reach criterion performance. Subsequently, it was observed that EGb 761-induced stimulus control is significantly antagonized by the selective S-HT1A antagonist WAY 100635, but is unaffected by the 5-HT2 antagonist pirenperone. Furthermore, EGb 761 generalized to the selective 5-HT1A agonist, 8-hydroxy-dipropylaminotetralin [8-OH-DPAT], and this generalization was blocked by WAY-100635. The present results indicate that EGb 761 is able to induce stimulus control when administered via the intraperitoneal route, and that its stimulus effects are mediated in part by activity at the 5-HT1A receptor. (C) 1999 Elsevier Science Inc.

Ondrizek, R. R., P. J. Chan, et al. (1999). Inhibition of human sperm motility by specific herbs used in alternative medicine. Journal Of Assisted Reproduction And Genetics. Feb 16(2): 87-91.

Purpose: Our purpose was to analyze sperm motility parameters in the presence of herbs.Methods: Washed sperm were incubated in either saw-palmetto (Serenoa repens, Permixon Sabal serrulatum), echinacea purpura, ginkgo biloba, St. John's wort (Hypericum perforatum), or control medium. Parameters were measured on a Hamilton-Thorn analyzed after 1, 4, 24, and 48 hr or 37 degrees C.Results: Sperm motility was inhibited at the high concentration (0.6 mg/mL) of Sr. John's wort. Curvilinear velocities and hear cross frequencies also decreassed, but not hyperactivation. High-concentration saw-palmetto, echinacea, or ginkgo inhibited motility at 24 and 48 hrConclusions: A potent inhibition of sperm motility was seen in St. John's wort unrelated to changes in pH. Furthermore, sperm viability was compromised in St. John's wort, suggesting a spermicidal effect. Metabolic changes were observed in saw-palmetto-treated sperm. High-concentration echinacea purpura interfered,vith sperm enzymes. Ginkgo did not have an antioxidant effect on sperm motility.

Sasaki, K., S. Hatta, et al. (1999). Effects of bilobalide on gamma-aminobutyric acid levels and glutamic acid decarboxylase in mouse brain. European Journal Of Pharmacology. Feb 367(2-3): 165-173.

We have previously demonstrated that bilobalide, a constituent of the Ginkgo biloba extract, possesses anticonvulsant activity, and suggested that the mechanism of its anticonvulsant action involves modulation of gamma-aminobutyric acid (GABA)-related neuronal transmission. This study examined the effects of bilobalide on the level of GABA and glutamate, the activity and the amount of glutamic acid decarboxylase (EC 4.1.1.15), and the function of GABA(A) receptors in the hippocampus, cerebral cortex and striatum of the mouse. GABA levels, glutamic acid decarboxylase activity, and the protein amount of 67 kDa glutamic acid decarboxylase in the hippocampus of mice treated with bilobalide (30 mg/kg, p.o., once a day for 4 days) were significantly higher than those in controls. However, there were no significant differences in glutamate levels or, the number and the dissociation constants of GABA(A) receptors in the hippocampus between control and bilobalide-treated mice. These results suggest that the anticonvulsant effect of bilobalide is due to elevation of GABA levels, possibly through potentiation of glutamic acid decarboxylase activity and enhancement of the protein amount of 67 kDa glutamic acid decarboxylase by bilobalide. (C) 1999 Elsevier Science B.V. All rights reserved.

Ahlemeyer, B., A. Mowes, et al. (1999). Inhibition of serum deprivation- and staurosporine-induced neuronal apoptosis by Ginkgo biloba extract and some of its constituents. European Journal Of Pharmacology. Feb 367(2-3): 423-430.

Previous studies have already demonstrated that some constituents of an extract of Ginkgo biloba (EGb), such as ginkgolide B and bilobalide, protect cultured neurons from hypoxia- and glutamate-induced damage. This prompted us to investigate whether they were also able to inhibit neuronal apoptosis. We induced apoptosis in cultured chick embryonic neurons as well as in mixed cultures of neurons and astrocytes from neonatal rat hippocampus by serum deprivation and staurosporine. The increase in the percentage of apoptotic chick neurons from 12% in controls to 30% after 24 h of serum deprivation was reduced to control level by EGb (10 mg/l), ginkgolide B (10 mu M), ginkgolide J (100 mu M) and bilobalide (1 mu M). After treatment with staurosporine (200 nM) for 24 h we observed 74% apoptotic chick neurons. This percentage of apoptotic neurons was reduced to 24%, 62% and 31% in the presence of EGb (100 mg/l), ginkgolide J (100 mu M) and ginkgolide B (10 mu M), respectively. Bilobalide (10 mu M) decreased apoptotic damage induced by staurosporine treatment for 12 h nearly to the control level. In mixed neuronal/glial cultures, the extract of EGb (100 mg/l) and bilobalide (100 mu M) rescued rat neurons from apoptosis caused by serum deprivation, whereas, bilobalide (100 mu M) and ginkgolide B (100 mu M) reduced staurosporine-induced apoptotic damage. Ginkgolide A revealed no anti-apoptotic effect in either serum-deprived or staurosporine-treated neurons. Our results suggest that EGb and some of its constituents possess anti-apoptotic capacity and that bilobalide is the most potent constituent. (C) 1999 Elsevier Science B.V. All rights reserved.

Maggini, F., R. Marrocco, et al. (1998). Lengths and nucleotide sequences of the internal spacers of nuclear ribosomal DNA in gymnosperms and pteridophytes. Plant Systematics And Evolution 213(3-4): 199-205.

The nucleotide sequences of the internal transcribed spacers (ITS1 and ITS2) of the nuclear ribosomal DNA were analyzed in species belonging to gymnosperms and pteridophytes. The lengths of the ITSs of sixteen species of gymnosperms and seven species of pteridophytes were estimated. The gymnosperms have ITS1 regions larger than those observed in the pteridophytes and angiosperms (ca. 610-3100 bp versus 159-360 bp). On the other hand, the ITS2 regions appear to be of a conserved length (182-370 bp). We have determined the complete nucleotide sequences of ITS regions from four gymnosperm species and five pteridophyte species by cloning the PCR products. Sequence analysis showed the presence of three short tandem arranged subrepeats of about 70 bp in the 1112 bp ITS1 of Ephedra fragilis. Pyrimidine rich (about 90%) DNA segments of 40-50 bp were observed in the ITS1 of Ginkgo biloba. A highly conserved 16 bp long sequence known to be present in the ITS1 of the angiosperm species has been also found in the ITS1 of Cycas revoluta, Taxus baccata and Ephedra fragilis.

Watson, D. G. and E. J. Oliveira (1999). Solid-phase extraction and gas chromatography mass spectrometry determination of kaempferol and quercetin in human urine after consumption of Ginkgo biloba tablets. Journal Of Chromatography B. Feb 723(1-2): 203-210.

A method was developed for the quantification of the flavonoids quercetin and kaempferol in human urine using a solid-phase extraction procedure followed by gas chromatography-mass spectrometry. Deuterated internal standards of the analytes were spiked into the samples prior to extraction. The limit of detection of the method was ca. 10 pg on column and precision of the method for quantification in a sample of urine was +/-9.40% for kaempferol and +/-7.34% for quercetin (n=6). The levels of quercetin and kaempferol found in urine samples were only a small fraction of the amount ingested. The treatment of urine samples with beta-glucuronidase markedly increased the levels of flavonoids detected, supporting the view that kaempferol and quercetin are eliminated in the urine as glucuronides. (C) 1999 Elsevier Science B.V. All rights reserved.

Kubo, J., J. R. Lee, et al. (1999). Anti-Helicobacter pylori agents from the cashew apple. Journal Of Agricultural And Food Chemistry. Feb 47(2): 533-537.

Anacardic acids and (E)-2-hexenal characterized from the cashew Anacardium occidentale L. (Anacardiaceae) apple have been found to exhibit antibacterial activity against the Gram-negative bacterium Helicobacter pylori, which is now considered to cause acute gastritis. The same antibacterial compounds have also been found to inhibit urease (EC 3.5.1.5).

Ondrizek, R. R., P. J. Chan, et al. (1999). An alternative medicine study of herbal effects on the penetration of zone-free hamster oocytes and the integrity of sperm deoxyribonucleic acid. Fertility And Sterility. Mar 71(3): 517-522.

Objective: To analyze the effects of certain herbs on sperm DNA and on the fertilization process.Design: Prospective comparative study.Setting: Clinical and academic research environment.Patient(s): Donor sperm specimens.Intervention(s): Zona-free hamster oocytes were incubated for 1 hour in saw palmetto (Serenoa repens), echinacea purpura, ginkgo biloba, St. John's wort (Hypericum perforatum), or control medium before sperm-oocyte interaction. The DNA of herb-treated sperm was analyzed with denaturing gradient gel electrophoresis.Main Outcome Measure(s): Oocyte penetration and integrity of the sperm BRCA1 exon 11 gene.Result(s): Pretreatment of oocytes with 0.6 mg/mL of St. John's wort resulted in zero penetration. A lower concentration (0.06 mg/mL) had no effect. High concentrations of echinacea and ginkgo also resulted in reduced oocyte penetration. Exposure of sperm to echinacea purpura and St. John's wort resulted in DNA denaturation. In contrast, saw palmetto and ginkgo had no effect. Sperm exposed to 0.6 mg/mL of St. John's wort showed mutation of the BRCA1 exon 11 gene.Conclusion(s): High concentrations of St. John's wort, echinacea, and ginkgo had adverse effects on oocytes. Saw palmetto had no effect. The data suggested that St. John's wort, ginkgo, and echinacea at high concentrations damage reproductive cells. St. John's wort was mutagenic to sperm cells. (Fertil Steril(R) 1999; 71:517-22. (C) 1999 by American Society for Reproductive Medicine.)

Heinze, G. and M. Ontiveros (1998). Phytopharmacology as an alternative treatment in psychiatry. Salud Mental. Dec 21(6): 33-42.

Phytomedicines for the treatment of different diseases have been used since a long time ago, but the discovery of synthetic dregs, like sulphas, peniciline and others antibiotics, disminshed the popularity of traditional medicine. In this work we explain why the interest on medical plant extracts surged again.We describe the pharmacodynamic and the pharmacokinetic aspects of three phytomedicines: Hypericum perforatum (Saint John's flower) for depression, Piper-methysticum (Kava-kava) for anxiety and Ginkgo biloba, for dementia.

Trovero, F., D. Brochet, et al. (1999). Ginkgo biloba extract EGb761 reduces the development of amphetamine-induced behavioral sensitization: effects on hippocampal type II corticosteroid receptors. Brain Research. Feb 818(1): 135-139.

Pretreatment of rats with the extract of Ginkgo biloba termed EGb761 reduced the behavioral sensitization induced by successive D-amphetamine administrations (0.5 mg/kg) as estimated by increasing values of locomotor activity. EGb761 pretreatment also prevented the reduced density of [H-3]dexamethasone binding sites in the dentate gyrus and the CA1 hippocampal regions of D-amphetamine treated animals. These observations suggest that EGb761, by reducing glucocorticoid levels, could modulate the activity of the neuronal systems involved in the expression of the behavioral sensitization. (C) 1999 Elsevier Science B.V. All rights reserved.

Khalsa, D. S. (1998). Integrated medicine and the prevention and reversal of memory loss. Alternative Therapies In Health And Medicine. Nov 4(6): 38-43.

This article, based on scientific research and clinical observations, suggests that memory lass is not an inevitable consequence of aging and that Alzheimer's disease can be prevented and reversed using an integrated medical approach. Three nai, associations with memory loss other than age, heredity, and genetics are described They include a high-fat diet, chronic unbalanced stress with ils attendant risk in the adrenal hormone cortisol, and the presence of cardiovascular disease. A 4-pillar integrative medical program on brain longevity is presented. The program includes a diet consisting of 15% fat and supplementation with brain-specific nutrients such as vitamin B complex, vitamin E, ubiquinone, ginkgo biloba, and phosphatidylserine. In addition, stress-relieving meditation, mind-body and cognitive exercise, antiaging drugs like L-deprenyl citrate, as well as hormones such as dehydroepiandrosterone and pregnenolone complete the program. Patient benefits such as greater wisdom and spiritual happiness are also explored.

Itil, T. M., E. Eralp, et al. (1998). The pharmacological effects of Ginkgo biloba, a plant extract, on the brain of dementia patients in comparison with tacrine. Psychopharmacology Bulletin 34(3): 391-397.

In 1994, a standardized dry extract of Ginkgo biloba leaves (SeGb), has been approved by German health authorities for the treatment of primary degenerative dementia and vascular dementia. More than 24 different brands of Ginkgo biloba extract are sold in the United States. Tac ri ne, a Iso known as tetrahydroaminoacrine (THA), and donepezil are currently the only drugs approved in the United States for the treatment of Alzheimer's disease. Previous studies demonstrated that SeGb and tacrine induce significant pharmacological effects on the brains of young, healthy human males, as determined by bioelectrical activity measurements obtained using the quantitative pharmaco-electroencephalogram (QPEEG(R)) method. The type of central nervous system (CNS) effects we have seen on computer-analyzed EEGs (CEEGs(R)) after administration of tacrine or EGb suggests both are "cognitive activators" which are, as a class of products, characterized by a (prepost) relative increase of 7.5 to 13 Hz ("alpha") and decrease of 1.3 to 7.5 Hz ("delta" end "theta") activity.To determine whether EGb or tacrine had noticeable pharmacological effects on elderly subjects diagnosed with possible or probable Alzheimer's, the present open, uncontrolled trial was conducted. Data from 18 subjects (11 males, 7 females) at an average age of 67.4 years with light to moderate dementia (Mini Mental mean score = 23.7, ranges: 15-29 [Geriatric Depression Scale mean scores = 3.7; range: 3.2-5.4]) were analyzed for this presentation, Each subject was randomly administered a single oral "Test-Dose(R)" of either 40 mg of tacrine or 240 mg of EGb2in two separate sessions within 3- to 7-day intervals. Before drug administration and at 1- and 3-hour intervals after drug administration, CEEGs were recorded for a minimum of 10 minutes. The CEEGs were analyzed using Period Analysis programs we developed for QPEEG.The results indicated that both EGb and, to a lesser degree, tacrine induced pharmacological effects, as established by QPEEG measurements, in the CNS similar to those previously established in healthy, young subjects. The type of CNS effects produced by EGb (as established by HZI's CEEG psychotropic drug database) in elderly dementia patients were similar to those induced by tacrine responders as well as those seen after the administration of other "cognitive activators" (pramiracetam, vinpocetine, BMY21502, suloctidil, and lisuride) and anti-dementia drugs approved in the United States or Europe (tacrine, donepezil, nimodipine, piracetam, and oxiracetam) from our database. The results also showed that 240 mg of EGb has typical cognitive activator CEEG profiles (responders) in more subjects (8 of 18) than 40 mg tacrine (3 of 18 subjects). Because of the small sample size, we could not test the hypothesis that subjects who showed cognitive activator-type pharmacological response to the first Test-Dose(R) of EGb or tacrine also exhibit more therapeutic effects (compared to nonresponders) when drugs are administered chronically.

Nakao, Y., S. Shiozaki, et al. (1999). Changes in carbohydrate and water content with ovule growth of Ginkgo biloba L. Journal Of Horticultural Science And Biotechnology. Jan 74(1): 60-63.

The carbohydrate and water contents of the ovule of Ginkgo biloba L. (ginkgo) were evaluated during its development. The ovule grew rapidly (stage I) after pollination in early May, temporarily stopped growing, in mid-July (stage II), and resumed growth slowly (stage III) from mid-August until maturation. The water content in the endosperm and outer integument were highest in June, and decreased thereafter, accompanied by ovule development. In the endosperm, the sugar content decreased rapidly during stage I, followed by a rapid increase in the starch content which is high level in early September. In the outer integument, the sugar content increased in early June, and remained nearly constant until early August. Then it transiently decreased in mid-August, when meso-integument hardening was completed, followed by a rapid increase. The starch content in the outer integument was low, but peaked in mid-August, when the sugar content was lowest. Although ginkgo nuts are usually harvested in October, we recommend early harvest in late August when starch accumulation in the endosperm, an important factor influencing the taste of ginkgo nuts, is at a high level.

Steinberg, M. (1999). Pharmacologic treatment of Alzheimer's disease: An update on approved, unapproved therapies. Formulary . Jan 34(1): 32-34.

This article reviews Various approved and nonapproved therapies for Alzheimer's disease (AD) and offers recommendations for their clinical use. The cholinesterase inhibitors tacrine and donepezil are the only FDA-approved drugs for AD. While both offer modest benefit in cognition and functioning, donepezil is the first-line agent because of its ease of dosing, better side effect profile, and lack of monitoring requirements. Several other cholinesterase inhibitors are in late-stage development. Clinicians may also consider other agents as supplements to cholinesterase inhibitors in appropriate patients. Vitamin E and selegiline may slow functional decline in AD patients, possibly via their antioxidant properties, and Ginkgo biloba extracts may have mild cognitive benefits. Nonsteroidal anti-inflammatory drugs and estrogen are being studied for their potential to halt, delay, or prevent AD progression.

Klepser, T. B. and M. E. Klepser (1999). Unsafe and potentially safe herbal therapies. American Journal Of Health System Pharmacy. Jan 56(2): 125-138.

Unsafe and potentially safe herbal therapies are discussed.The use of herbal therapies is on the rise in the United States, but most pharmacists are not adequately prepared educationally to meet patients' requests for information on herbal products. Pharmacists must also cope with an environment in which there is relatively little regulation of herbal therapies by FDA. Many herbs have been identified as unsafe, including borage, calamus, coltsfoot, comfrey, life root, sassafras, chaparral, germander, licorice, and ma huang. Potentially safe herbs include feverfew, garlic, ginkgo, Asian ginseng, saw palmetto, St. John's wort, and valerian. Clinical trials have been used to evaluate feverfew for migraine prevention and rheumatoid arthritis; garlic for hypertension, hyperlipidemia, and infections; ginkgo for circulatory disturbances and dementia; ginseng for fatigue and cancer prevention; and saw palmetto for benign prostatic hyperplasia. Also studied in formal trials have been St. John's wort for depression and valerian for insomnia. The clinical trial results are suggestive of efficacy of some herbal therapies for some conditions. German Commission E, a regulatory body that evaluates the safety and efficacy of herbs on the basis of clinical trials, cases, and other scientific literature, has established indications and dosage recommendations for many herbal therapies.Pharmacists have a responsibility to educate themselves about herbal therapies in order to help patients discern the facts from the fiction, avoid harm, and gain what benefits may be available.

Shadlen, M. F. and E. B. Larson (1999). What's new in Alzheimer's disease treatment? Reasons for optimism about future pharmacologic options. Postgraduate Medicine. Jan 105(1): 109-118.

There is reason for optimism about future treatment options for Alzheimer's disease, despite uncertainties about which subgroups of patients will respond to treatment, the magnitude of therapeutic effects, the duration of benefit, and the long-term outcomes from disease-modifying agents. Because Alzheimer's disease is a heterogeneous disorder, the range of treatment responses likely will remain variable. The decision to initiate treatment must be individualized to the therapeutic goals of the patient and his or her caregiver.Advances in the understanding of the pathogenesis of Alzheimer's disease have led to new treatment strategies. Augmentation of cholinergic function through the use of acetylcholinesterase inhibitors with favorable side-effect profiles (eg, donepezil, possibly metrifonate) can create the potential for improved memory and cognition. Anti-inflammatory drugs, estrogen, alpha-tocopherol, selegiline, and ginkgo biloba are the subject of ongoing clinical trials to determine their effectiveness in Alzheimer's disease. Future treatment strategies will likely include a combination of acetylcholinesterase inhibitors and disease-modifying agents. A greater understanding of the pathogenesis of Alzheimer's disease may lead to the development of new neuroprotective agents. The longterm human and social costs, as well as potential benefits, of prolonging the natural course of the disease can only become evident with study of these agents in years to come.(24)

Mosle, B., M. E. Collinson, et al. (1998). Factors influencing the preservation of plant cuticles: a comparison of morphology and chemical composition of modern and fossil examples. Organic Geochemistry 29(5-7): 1369-1380.

Samples of Recent Ginkgo biloba, two Cretaceous Ginkgo and two Cretaceous conifer cuticles from different enclosing lithologies but with similar thermal maturity of the fossils, have been analysed by scanning and transmission electron microscopy (SEM, TEM), Fourier transform-infrared spectroscopy (FT-IR), and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). Recent and Fossil Ginkgo cuticles under SEM reveal sheets, similar in appearance, varying in the abundance and texture of the cuticular papillae. TEM of the Recent Ginkgo shows an outer amorphous cuticle layer, a structured middle layer and an inner laminated layer of cell wall. The Cretaceous Ginkgo cuticles retain the amorphous layer and a modified structured layer. SEM of Cretaceous Abletites and Frenelopsis also shows preservation of cuticle sheets but each has distinctive morphology. These conifer cuticles are very thick (TEM), Frenelopsis cuticle has remarkable multilaminar ultrastructure whilst Abietites amorphous. G. biloba cuticle consists mainly of the natural polyester, cutin, as revealed by FT-IR and pyrolysis, indicated by an abundance of saturated, unsaturated and hydroxy fatty acids. IR spectra of fossil cuticles, like modern cuticles, show aliphatic C-H, hydroxyl and carbonyl functions. However, in fossils, the carbonyl ester is transformed to carboxylic acid or ketone groups. Pyrolysates of fossils show phenolic constituents like modern cuticles but loss of cutin fatty acid monomers and an increased prominence of an homologous series of n-alkene and n-alkane fragments up to n-C-30 Since most Recent cuticles, including those of conifers and Ginkgo biloba which we have studied, do not yield a non-saponifiable highly resistant residue it is proposed that organic preservation of fossil species investigated involves the diagenetic stabilisation of chemically-labile aliphatic cutin constituents along with incorporation of waxes. These general chemical modifications characterise all fossil Ginkgo and conifer cuticles, irrespective of their enclosing lithology, systematic affinity, external morphology or internal ultrastructural preservation. However there are also clear chemical differences between the fossil samples which may relate to their systematic affinity (ginkgos vs Abietites and Frenelopsis). (C) 1998 Elsevier Science Ltd. All rights reserved.

Balon, R. (1999). Ginkgo biloba for antidepressant-induced sexual dysfunction? Journal Of Sex And Marital Therapy. Jan Mar 25(1): 1-2.

Houghton, P. J. (1999). Roots of remedies: plants, people and pharmaceuticals. Chemistry And Industry. Jan 4(1): 15-19.

Tu, T. T. N., H. Bocherens, et al. (1999). Ecological distribution of Cenomanian terrestrial plants based on C-13/C-12 ratios. Palaeogeography Palaeoclimatology Palaeoecology. Jan 145(1-3): 79-93.

The Cenomanian lagoonal member of the 'Argiles du Baugeois' (Anjou, France) yielded a rich and exceptionally well-preserved fossil leaf flora. Stable carbon isotope ratios of fossil plants were measured in order to investigate the presence of a palaeoenvironmental signal. The small intraspecies variations of delta(13)C values observed for most of the fossil leaves suggested that the isotopic signal had not been significantly altered. Hence, an isotopic approach was used as an attempt to assist in reconstructing the ecological distribution of the flora. The C-13-enrichment of the fossil leaves suggested that the plants underwent water or salt stress. The occurrence of the conifer Frenelopsis suggested, at least locally, a saline environment such as a lagoon. According to their decreasing delta(13)C values, all the plants collected could have been distributed along a decreasing salinity transect from the lagoon to a flood plain. The predominant species, Eretmophyllum andegavense, a fossil ginkgo, exhibited a wide range of delta(13)C values. This could indicate that this taxon grew in a wide range of habitats with varying salinities. The origin of the organic matter appeared to be terrestrial with a major contribution from water-stressed plants such as Frenelopsis, as suggested by the similarity between delta(13)C values of the conifer and the sedimentary organic matter. delta(13)C values of the sediment indicated stable palaeoenvironmental conditions during the deposition of the 'Argiles du Baugeois' member. Hence, while detailed palaeovegetation reconstructions are generally limited to the few deposits which present in-situ palaeoflora, the contribution of isotope geochemistry could allow reconstructions for a wider range of fossil plant deposits. (C) 1999 Elsevier Science B.V. All rights reserved.

Inoue, H., S. Kamoda, et al. (1998). Ginkgolide production in relation to organogenesis in Ginkgo biloba. Journal Of Wood Science 44(5): 375-378.

The contents of diterpenoids, ginkgolides A, B, and C, in seeds, embryos, and plantlets of Ginkgo biloba were analyzed to clarify the relations between organogenesis and terpene contents in G. biloba. There is so far no published report on the contents and changes in such terpenes in seeds and very young plantlets of G. biloba. Ginkgolides were present in seeds and embryos. Plantlets cultured in both the dark and under illumination contained substantial amounts of ginkgolides, more abundant than in seeds and embryos. It is concluded that ginkgo yields ginkgolides in its early stage of development regardless of light.

Akiba, S., T. Kawauchi, et al. (1998). Inhibitory effect of the leaf extract of Ginkgo biloba L. on oxidative stress-induced platelet aggregation. Biochemistry And Molecular Biology International. Dec 46(6): 1243-1248.

The effect of the leaf extract of Ginkgo biloba L. on platelet aggregation induced by oxidative stress was studied. The extract caused a dose-dependent inhibition of platelet aggregation stimulated with tert-butyl hydroperoxide (t-BHP) and Fe2+. Similar inhibitory activity was observed when platelets were exposed to H2O2 and Fe2+. Synergistic aggregation induced by a combination of t-BHP and Fe2+ or H2O2 and Fe2+ in association with suboptimal concentration of collagen or U46619, was prevented by the extract. However, the extract failed to inhibit aggregation in response to collagen, thrombin or U46619. Ginkgolides A, B and C inhibited platelet-activating factor-induced aggregation, but not oxidant-induced aggregation. These data suggest that the suppressive effect of the extract is specific on platelet aggregation stimulated by oxidative stress, and that this effect is involved in the mechanism related to its protective effect upon cerebral or myocardial injuries.

Janssens, D., C. Michiels, et al. (1999). Increase in circulating endothelial cells in patients with primary chronic venous insufficiency: Protective effect of Ginkor Fort in a randomized double-blind, placebo-controlled clinical trial. Journal Of Cardiovascular Pharmacology. Jan 33(1): 7-11.

One possible mechanism that accounts for the alterations observed in varicose veins is the activation of endothelial cells by ischemia occurring in the leg veins during blood stasis and the cascade of reactions that follows. Because in vitro data suggest that endothelium alteration is a key event in the development of the pathology, it was important to confirm this hypothesis in patients. We used the number of circulating endothelial cells detached from the vascular wall as a criterion of the endothelium injury. We first compared the number of circulating endothelial cells (CECs) in patients with chronic venous insufficiency (CVI) with those of a control population. A twofold increase in the CEC count (1,001 +/- 127 CEC/ml of plasma compared with 514 +/- 82 CECs/ml) was observed in CVI patients, which indeed suggests an alteration of the endothelium in this disease. Second, the protective effect of a venotropic drug, Ginkgo biloba extract, troxerutine, and heptaminol (Ginkor Fort), was tested by a randomized double-blind, placebo-controlled clinical trial. In the active-treatment group, the mean values of the CEC count decreased by 14.5% after a 4-week treatment, whereas in the placebo group, the decrease was less (8.4%). The decrease from week 0 to the end of treatment was significantly higher in the active-treatment group than in the placebo group. These results confirm the important role of the endothelium alterations in the development of varicose veins and suggest a potential beneficial action of a venotropic drug on the venous wall.

Perry, E. K., A. T. Pickering, et al. (1998). Medicinal plants and Alzheimer's disease: Integrating ethnobotanical and contemporary scientific evidence. Journal Of Alternative And Complementary Medicine. Win 4(4): 419-428.

The use of complementary medicines such as plant extracts in dementia therapy, varies according to the different cultural traditions. In orthodox Western medicine, contrasting with that in China and the Far East for example, pharmacological properties of traditional cognitive or memory enhancing plants have not been widely investigated in the context of current models of Alzheimer's disease. An exception is Ginkgo biloba in which the ginkgolides have antioxidant, neuroprotective, and cholinergic activities relevant to Alzheimer's disease mechanisms. The therapeutic efficacy of Ginkgo biloba extracts in Alzheimer's disease in placebo-controlled clinical trials is reportedly similar to currently prescribed drugs such as tacrine or donepezil and, importantly, undesirable side effects of Ginkgo biloba are minimal. Old European reference books (eg, medical herbals) document a variety of other plants such as Salvia officinalis (sage) and Melissa officinalis (balm) with memory improving properties, and cholinergic activities have recently been identified in extracts of these plants. Precedents for modern discovery of clinically relevant pharmacological activities in plants with long-established medicinal use include, for example, the interaction of alkaloid opioids in Papaver somniferum (Opium poppy) with endogenous opiate receptors in the brain. With recent major advances in understanding the neurobiology of Alzheimer's disease, and as yet limited efficacy of so-called rationally designed therapies, it may be timely to re-explore historical archives for new directions in drug development. This article considers not only the value of an integrative traditional and modern scientific approach to developing new treatments for dementia, but also in the understanding of disease mechanisms. Long before the current biologically based hypothesis of cholinergic derangement in Alzheimer's disease emerged, plants now known to contain cholinergic antagonists were recorded for their amnesic and dementia-inducing properties.

Winther, K., C. Randlov, et al. (1998). Effects of Ginkgo biloba extract on cognitive function and blood pressure in elderly subjects. Current Therapeutic Research Clinical And Experimental. Dec 59(12): 881-888.

In this randomized, double-masked study, we assessed the effects of a Ginkgo biloba (GB-8) extract on elderly volunteers with age-related cognitive dysfunction. A total of 260 subjects were tested to obtain a homogeneous group of 60 elderly subjects with mild-to-moderate cognitive impairment, as defined by a clinical rating scale. The subjects were allocated to one of three groups and received either GB-8 40 mg or 80 mg or placebo three times daily for 3 months. Before therapy was started and after 1 and 3 months of treatment, standardized testing of attention, concentration, and memory was performed. The subjects completed self-assessments before and after 3 months of therapy, and arterial blood pressure was measured at the same intervals. Clinical ratings were done before and after 3 months of treatment. Six subjects withdrew from the study, whereas 54 subjects (31 women and 23 men; mean age, 74 years; age range, 61 to 88 years) completed the study. After randomization, the groups were similar with respect to age, social class, level of education, and demographic characteristics. Objective test results showed that attention, concentration, and short-term verbal memory improved significantly in subjects receiving the low-dose (standard) treatment. Similar improvements were seen in the results of the self-assessment test and the clinical rating. Diastolic blood pressure decreased significantly during low-dose treatment. Treatment with the GB-8 extract was found to improve objective measures of cerebral function in elderly subjects with mild-to-moderate cognitive impairment; the improvement appeared to be clinically relevant. The possible antihypertensive action of Ginkgo biloba extract is sufficient to warrant further investigation.

Viola, H., M. Marder, et al. (1998). Central nervous system effects of natural and synthetic flavonoids. Anales De La Asociacion Quimica Argentina. May Dec 86(3-6): 229-236.

Flavonoids are naturally occurring molecules present in the human diet. We demonstrate that some flavonoids possess central nervous system effects acting through the central benzodiazepine receptors. The pharmacological characterization of chrysin (5,7-dihydroxyflavone) and apigenin (5,7,4'-trihydroxyflavone), isolated from Passiflora coerulea and Matricaria recutita, respectively showed their anxiolytic, but not myorelaxant or amnesic effects. Cirsiliol (5,3',4'-trihydroxy-6,7-dimethoxyflavone), however isolated from Salvia guaranitica, had sedative-depressant properties. We were able to increase the biochemical and pharmacological potency of the natural flavonoids by means of the addition of halo and/or nitro groups to the flavone nucleus. Some flavonoids are partial agonists of the benzodiazepine receptors and may become new therapeutic drugs, devoid of the unwanted side effects of classical benzodiazepines.

Baudouin, C., P. J. Pisella, et al. (1999). Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical. Graefes Archive For Clinical And Experimental Ophthalmology. Jan 237(1): 58-66.

Background: A study was carried out to investigate the effect of two antioxidants - Ginkgo biloba extract (EGb761) and superoxide dismutase (SOD)- in an experimental model of vitreoretinopathy obtained by direct production of oxygen free radicals in the vitreous cavity. Methods: Twenty-eight pigmented rabbits were used. Vitreoretinopathy was induced by intravitreal injection of 50 mu l of a mixture composed of 40 nmol of xanthine and 0.001 IU of xanthine oxidase. Rabbits were randomly distributed into four groups: Group 1 (n=8) did not receive any treatment and served as a positive control. Groups 2 (n=8) and 3 (n=8) received for 1 month EGb761 given orally at a dose of 100 mg/kg/day, respectively 1 day after and 1 week before induction of retinopathy. Group 4 (n=4) was treated by three intramuscular injections of 15 000 IU/kg of SOD, 24 h before induction and 24 and 48 h thereafter. Clinical evaluations and electroretinograms (ERG) were repeatedly performed until the animals were killed at day 28. Histological examinations and immunohistological procedures were performed to ascertain the origin and characteristics of the cellular proliferation and to compare vitreoretinal structures in the four groups. Results: Intravitreal injection of xanthine-xanthine oxidase produced a strong inflammatory response with vitreous infiltrates and epiretinal membrane formation, inconstantly associated with retinal detachment. ERG showed a decrease of the a-, b- and c-waves beginning within a few hours after injection. Histologic evaluation found an intravitreal and epiretinal infiltration by leukocytes and epithelial-derived cells, dense vitreoretinal membranes and retinal detachments with occasional neovascularization. In the treated groups (groups 2-4), all clinical, electric and histologic data were significantly improved compared to the control group. However, no difference could be found among the three treated groups. Conclusion: This study demonstrates the strong pathologic effects of free radical production on the retina and the close relationships between free radicals, inflammatory pathways and vitreoretinal proliferative disorders. It also confirms the pharmacological interest of prevention by antioxidants and free radical scavengers.

Mast, C. (1998). Ginkgo for treatment of tinnitus - Commentary. Forschende Komplementarmedizin. Oct 5(5): 251-252.

Rapin, J. R., M. Zaibi, et al. (1998). In vitro and in vivo effects of an extract of Ginkgo biloba (EGb 761), ginkgolide B, and bilobalide on apoptosis in primary cultures of rat hippocampal neurons. Drug Development Research. Sep 45(1): 23-29.

Primary cultures of rat hippocampal neurons were prepared and exposed to increasing concentrations of a peroxyl radical-generator, 2,2'-azobis 2 amidinopropane (AAPH). Addition of AAPH (20 or 50 mM) to the medium caused a decrease in cell viability and an increase in the number of apoptotic cells. Values for the number of nucleosomes were obtained using an ELISA technique. "Factor F," an indicator of enrichment in nucleosomes, was found to be directly proportional to the number of neuronal apoptoses. Addition of an extract of Ginkgo biloba (EGb 761; 5-20 mu g/ml) or ginkgolide B (one of its terpenoid constituents; 0.2 or 0.4 mu g/ml) to the culture medium in vitro led to increases in cell viability and decreases in the number of hippocampal cells undergoing AAPH-induced apoptosis, whereas addition of bilobalide (another terpenoid constituent of EGb 761; 0.1-1.0 mu g/ml) was ineffective. These in vitro results were corroborated and extended when these same substances were administered to rats in vivo. Oral administration of EGb 761 (50 mg/kg/day) for 8 days caused a significant increase in cell viability and a highly significant decrease in the numbers of both spontaneously occurring and AAPH-induced apoptoses. Similar protective effects were observed with ginkgolide B (2 mg/kg/day, p.o.), whereas bilobalide (2 mg/kg/day, p.o.) was ineffective. As AAPH enhances the production of peroxyl radicals, the protective actions of subacute in vivo treatments with EGb 761 and ginkgolide 8 appear to be associated with an anti-lipoperoxidative effect of these substances. Drug Dev. Res. 45:23-29, 1998. (C) 1998 Wiley-Liss, Inc.

Pitchumoni, S. S. and P. M. Doraiswamy (1998). Current status of antioxidant therapy for Alzheimer's disease. Journal Of The American Geriatrics Society. Dec 46(12): 1566-1572.

Accumulating evidence from preclinical and clinical studies supports the hypothesis that oxidative stress may be associated with the onset and progression of Alzheimer's Disease (AD). Antioxidant therapies are being promoted in the lay press to enhance mental functions and delay cognitive losses with aging. An increasing number of physicians are also recommending antioxidant therapies, such as high dose vitamin E, for subjects with AD and other neurodegenerative disorders. High dose vitamin E, ginkgo biloba, and selegiline are three putative antioxidants that have been tested in randomized multicenter trial conditions in the US. This paper summarizes the oxidative stress hypothesis of AD and reviews the strengths and limitations of published antioxidant studies in AD in relation to the role of such therapies in practice.

Hodisan, T., M. Culea, et al. (1998). Separation, identification and quantitative determination of free amino acids from plant extracts. Journal Of Pharmaceutical And Biomedical Analysis. Nov 18(3): 319-323.

This research presents the results obtained from the separation, identification and quantitative determination of free amino acids from Gingko biloba and Hedera helix leaf extracts, using three modem techniques: thin layer chromatography (TLC), high performance liquid chromatography (HPLC), and gas chromatography-mass spectrometry. The presence of the determined amino acids explains the utilisation of G. biloba and H. helix leaf extracts in cosmetic and pharmaceutical products. (C) 1998 Elsevier Science B.V. All rights reserved.

Rosler, M., W. Retz, et al. (1998). Free radicals in Alzheimer's dementia: currently available therapeutic strategies. Journal Of Neural Transmission 54: 211-219.

Substantial evidence now exists that oxidative stress may play an important role in the etiopathogenesis of DAT. The different sources of oxidative stress in DAT are suggesting several pharmacological opportunities for influencing the disease. It is possible to distinguish 2 major types of possible therapeutic agents according to their pharmacological. point of attack.1. Radical scavengers, agents directly interacting with free radicals. Candidates of this type are gingko biloba, vitamins A, C, E and estrogen.2. Antioxidants, which are able to prevent or decrease the production of free radicals by use of specific neuropharmacological properties. Candidates are selegiline, a MAO-B inhibitor well established in the therapy of Parkinson's disease, and tenilsetam, which is believed to be an AGE-inhibitor.Recent in vitro studies have demonstrated the efficacy of both types of therapeutic agents by preventing or delaying oxidative neural damage.Some clinical data exist regarding the antidementive properties particularly in terms of gingko biloba, selegiline and vitamin E. The efficacy studies about these compounds seem to indicate a promising future strategy in the therapy of DAT. But it is too early to draw definite conclusions since it is well kown that all of our candidate substances do not act specifically as radical scavengers or antioxidants.

Wolff, R. L., F. Pedrono, et al. (1998). The seed fatty acid composition and the distribution of Delta 5-olefinic acids in the triacylglycerols of some taxaceae (Taxus and Torreya). Journal Of The American Oil Chemists Society. Nov 75(11): 1637-1641.

The fatty acid compositions of the seeds from three Taxus (yew) species and one Torreya species belonging to the Taxaceae family [Taxus cuspidata (Japanese yew), T. chinensis (Chinese yew), T. baccata (English yew), and Torreya grandis (Chinese nutmeg yew)] have been established. These compositions were compared with those previously published for T. canadensis (Canadian yew) and Torreya nucifera. in Taxus species, as well as in Torreya species, Delta 5-olefinic acids are present in the seed lipids from all species analyzed. In Taxus, 5,9-18:2 (taxoleic) acid is the prominent Delta 5-olefinic acid. It represents between 9.5 and 16.2% of total fatty acids. Other Delta 5-olefinic acids that occur in low amounts are 5,9,12-18:3 (<3.5%), 5,11-20:2 (<0.3%), 5,11,14-20:3 (<2.2%), and 5,11,14,17-20:4 (<0.3%) acids. In Torreya species, the major Delta 5-olefinic acid is 5,11,14-20:3 (sciadonic) acid (between 6.7 and 11.2%). In contrast to Taxus species, the 5,9-18:2 and 5,9,12-18:3 acids are scarce in Torreya species: less than 0.1%. Also, the 9,12,15-18:3 acid content is significantly lower in Torreya than in Taxus. The prominence of taxoleic acid among Delta 5-olefinic acids in the seed lipids is a unique characteristic of the genus Taxus that isolates it from all other Coniferophytes analyzed so far. However, this feature is not shared by other Taxaceae species, such as Torreya, and with regard to their seed fatty acid compositions, the family Taxaceae appears particularly heterogeneous. Our observations favor the hypothesis that in Gymnosperm seeds, there might exist two Delta 5-desaturases, one specific for unsaturated acids with a Delta 9-ethylenic bond (active in Taxus but not in Torreya), and the other specific for unsaturated acids with a Delta 11-ethylenic bond (active in Torreya but not in Taxus). Our data also highlight the importance of the elongase(s) in the metabolism of fatty acids in Gymnosperm seeds. 14-Methylhexadecanoic acid, a habitual component of Pinaceae and Ginkgo biloba seed lipids, could not be detected in the Taxaceae studied here. C-13 nuclear magnetic resonance spectroscopy of the oils from both genera has confirmed that Delta 5-olefinic acids are apparently excluded from the internal position of triacylglycerols, which is a characteristic common to all Gymnosperm species analyzed so far, and consequently of great antiquity in their life history.

Wang, D. D., T. J. Girard, et al. (1998). Inhibitory activity of unsaturated fatty acids and anacardic acids toward soluble tissue factor-factor VIIa complex. Journal Of Natural Products. Nov 61(11): 1352-1355.

Five compounds, which inhibited the amidolytic activity of soluble tissue factor/activated factor VII complex (sTF/VIIa), were isolated from two traditional Chinese medicinal plants commonly used in the treatment of cardiovascular and cerebrovascular diseases; The active compounds were found to be linolenic, linoleic, and oleic acids from roots of Salvia miltiorrhiza; and two anacardic acids, 6-(8'Z-pentadecenyl)- and 6-(10'Z-heptadecenyl)-salicylic acids, from leaves of Ginkgo biloba. The IC50 values were in the range 30-80 mu mol/L. Palmitic acid, isolated from roots of Salvia miltiorrhiza, and 2-[(3',7',11',15'-tetramethyl)-2'E,6'E, 10'E,14'E-hexadecatetraenyl]-1,4-hydroquinone, isolated from the marine sponge Adocia viola, did not inhibit sTF/VIIa. Further expansion of the structure-activity relationship to include anacardic acids, 6-(8'Z,11'Z-heptadecadienyl)- and 6-(8'Z, 11'Z, 14'Z-heptadecatrienyl)-salicylic acids from leaves of Anacardium spondias, and other fatty acids demonstrated that at least one cis double bond was essential for inhibitory activity, and that fatty acids containing two or three cis double bonds were optimal. Evidence from preincubation studies implied that these fatty acids may exert their effect by binding to VIIa and consequently preventing binding of sTF to VIIa.

Saponara, R. and E. Bosisio (1998). Inhibition of cAMP-Phosphodiesterase by biflavones of Ginkgo biloba in rat adipose tissue. Journal Of Natural Products. Nov 61(11): 1386-1387.

This work compares the inhibition of cAMP-phosphodiesterase in rat adipose tissue by a mixture of Ginkgo biloba biflavones with the effect of individual dimeric flavonoids. The degree of enzyme inhibition by G. biloba biflavones was amentoflavone > bilobetin > sequoiaflavone > ginkgetin = isoginkgetin. Sciadopitysin was almost inactive.

Li, C. X., L. Li, et al. (1998). The protective effects of traditional Chinese medicine prescription, Han-Dan-Gan-Le, on CCl4-induced liver fibrosis in rats. American Journal Of Chinese Medicine 26(3-4): 325-332.

Han-Dan-Gan-Le, a Chinese medicine preparation composed of Salvia miltorrhiza, Radix paeoniae, Astragalus membranaceus, Stephania tetrandra, and dried leaves of Ginkgo biloba, has been used successfully to treat human liver fibrosis and cirrhosis for years. This study was designed to examine the mechanisms of the protection. Male Wistar rats were given CCl4 (1.2 ml/kg, 2 times/week), 20% fat diet, and 30% alcohol in drinking water (every other day) for 6 weeks. Han-Dan-Gan-Le (0.5 and 1.0 g/kg, p.o., daily for 6 weeks) was administered to rats simultaneously to examine the protective effects against CCl4-induced liver fibrosis. The experimentally-induced liver fibrosis and other morphological alterations were significantly ameliorated by Han-Dan-Gan-Le. Han-Dan-Gante treatments decreased CCl4-induced hepatic collagen accumulation by more than 50%, and significantly increased urinary excretion of hydroxyproline. The CCl4-induced lipid peroxidation in liver and serum was ameliorated as a result of Han-Dan-Gan-Le treatment, possibly by restoring the activity of superoxide dismutase activity in liver and erythrocytes, In conclusion, Han-Dan-Gan-Le is effective in protecting against liver fibrosis, The mechanisms of the protection appear to be due to its antioxidant properties and the modulation of hepatic collagen metabolism.

Jobst, K. A. (1998). Gingko for treatment of dementia. Forschende Komplementarmedizin. Apr 5(2): 93-95.

Schneider, B. (1998). Gingko for treatment of dementia. Forschende Komplementarmedizin. Apr 5(2): 95-96.

Cesarani, A., F. Meloni, et al. (1998). Ginkgo biloba (EGb 761) in the treatment of Equilibrium disorders. Advances In Therapy. Sep Oct 15(5): 291-304.

In an open, controlled study, 44 patients complaining of vertigo, dizziness, or both, caused by vascular vestibular disorders were randomly treated with extract of Ginkgo biloba (EGb 761) 80 mg twice daily or with betahistine dihydrochloride (BI) 16 mg twice daily for 3 months. A complete neuro-otologic and equilibrimetric examination was performed at baseline and after 3 months of treatment, with evaluation of clinical findings. In the first month of therapy, vertigo and dizziness improved in 64.7% of patients treated with BI and in 65% of those who received EGb 761. Compared to baseline, no statistically significant changes were observed in cranial scans for patients with a ''central'' cranial pattern. Likewise, no changes versus baseline were observed in both groups for the equilibrium score. The comprehensive test battery showed the following findings: EGb 761 induced a slight decrease of saccadic delay and considerably increased saccadic velocities; BI improved saccadic accuracy but did not modify delay; EGb 761 improved smooth pursuit gain at 0.4 Hz 40 degrees/s three times more than BI; both drugs asymmetrically reduced nystagmus maximum velocity at 40 degrees/s; both drugs asymmetrically improved the sinusoidal vestibule-ocular reflex; BI considerably reduced-whereas EGb 761 considerably improved-visuovestibular ocular reflex. No side effects were recorded during the trial except for transient mild headache and gastric upset in 2 patients receiving EGb 761 and transient cyanosis of nails and lips in 1 patient given BI. These results suggest that EGb 761 and BI operate at different equilibrium receptor sites and show that EGb 761 can considerably improve oculomotor and visuovestibular function.

Pietta, P., P. Simonetti, et al. (1998). Antioxidant activity of selected medicinal plants. Journal Of Agricultural And Food Chemistry. Nov 46(11): 4487-4490.

Commonly used medicinal plant extracts with standardized content of polyphenols were investigated for their total antioxidant activity(TAA). Green tea, oligomeric procyanidins (from grape seed and pine bark), bilberry, and ginkgo exhibited TAA in the range of 5.12-2.57 mM Trolox, thereby indicating a valuable antioxidant capacity. Witch hazel, propolis EPID, artichoke, and hawthorn afforded lower TAA (1.54-0.44 mM Trolox), whereas echinacea, ginseng, passionflower, sweet clover, and eleuthero were rather uneffective (TAA < 0.32 mM Trolox). Excipients normally used to prepare the extracts did not interfere with the assay, and a good correlation between the content of polyphenols and the TAA was assessed. The measured TAB was higher than those calculated from the content and antioxidant potential of specific components, as exemplified for green tea and ginkgo extracts. This may be attributed to the presence in these extracts of other substances with antioxidant capacity. On the other hand, some components (such as ginkgolides in ginkgo extract) insensitive to the TAA assay played an important antioxidant role in vivo. These results suggest that TAA determination is of interest for a comparative evaluation of in vitro antioxidant potential, but it needs to be combined with in vivo data for adequate assessment of the antioxidant capacity of medicinal plant extracts.

Oken, B. S., D. M. Storzbach, et al. (1998). The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Archives Of Neurology. Nov 55(11): 1409-1415.

Objective: To determine the effect of treatment with Ginkgo biloba extract on objective measures of cognitive function in patients with Alzheimer disease (AD) based on formal review of the current literature.Methods: An attempt was made to identify all English and non-English-language articles in which G biloba extract was given to subjects with dementia or cognitive impairment. Inclusion criteria for the meta-analysis were (1) sufficiently characterized patients such that it was clearly stated there was a diagnosis of AD by either Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, or National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, or there was enough clinical detail to determine this by our review; (2) clearly stated study exclusion criteria, ie, those studies that did not have stated exclusions for depression, other neurologic disease, and central nervous system-active medications were excluded; (3) use of standardized ginkgo extract in any stated dose; (4) randomized, placebo-controlled and double-blind study design; (5) at least 1 outcome measure was an objective assessment of cognitive function; and (6) sufficient statistical information to allow for meta-analysis.Results: Of more than 50 articles identified, the overwhelming majority did not meet inclusion criteria, primarily because of lack of clear diagnoses of dementia and AD. Only 4 studies met all inclusion criteria. In total there were 212 subjects in each of the placebo and ginkgo treatment groups. Overall there was a significant effect size of 0.40 (P<.0001). This modest effect size translated into a 3% difference in the Alzheimer Disease Assessment Scale-cognitive subtest.Conclusions: Based on a quantitative analysis of the literature there is a small but significant effect of 3- to 6-month treatment with 120 to 240 mg of G biloba extract an objective measures of cognitive function in ED. The drug has not had significant adverse effects in formal clinical trials but there are 2 case reports of bleeding complications. In AD, there are limited and inconsistent data that preclude determining if there are effects on noncognitive behavioral and functional measures as well as on clinician's global rating scales. Further research in the area will need to determine if there are functional improvements and to determine the best dosage. Additional research will be needed to define which ingredients in the ginkgo extract are producing its effect in individuals with AD.

Ohara, M., D. Kiefer, et al. (1998). A review of 12 commonly used medicinal herbs. Archives Of Family Medicine. Nov Dec 7(6): 523-536.

A large and increasing number of patients use medicinal herbs or seek the advice of their physician regarding their use. More than one third of Americans use herbs for health purposes, yet patients (and physicians) often lack accurate information about the safety and efficacy of herbal remedies. Burgeoning interest in medicinal herbs has increased scientific scrutiny of their therapeutic potential and safety, thereby providing physicians with data to help patients make wise decisions about their use. This article provides a review of the data on 12 of the most commonly used herbs in the United States. In addition, we provide practical information and guidelines for the judicious use of medicinal herbs.

Akisu, M., N. Kultursay, et al. (1998). Platelet-activating factor is an important mediator in hypoxic ischemic brain injury in the newborn rat. Biology Of The Neonate. Dec 74(6): 439-444.

Hypoxic-ischemic encephalopathy is still a very important cause of neonatal mortality and morbidity. Recently, platelet-activating factor (PAF) has been accused of being responsible for the neuronal damage in hypoxic-ischemic brain. We investigated tissue PAF concentrations in hypoxic-ischemic brain injury in immature rats. Endogenous PAF concentration in brain tissue showed a marked increase in hypoxic-ischemic pups (85.6 +/- 15.5 pg/mg protein) when compared to that of control (9.05 +/- 3.1 pg/mg protein). In addition, we examined the effects of flunarizine, a selective calcium channel blocker, and Ginkgo biloba extract (EGb 761) on endogenous PAF concentration in hypoxic-ischemic brain injury. Endogenous PAF concentrations in both flunarizine-pretreated (16.6 +/- 4.8 pg/mg protein) and EGb 761-pretreated (33.5 +/- 8.9 pg/mg protein) pups were significantly lower than the untreated group. These results indicate that PAF is an important mediator in immature rat model of cerebral hypoxic-ischemic injury. The suppressor effect of flunarizine and EGb 761 on PAF production may open new insight into the treatment of hypoxic-ischemic brain injury.

Knipschild, P. G., R. Hoerr, et al. (1998). Optimization of placebos for double-blind clinical trials - Experience with a phytopharmaceutical. Arzneimittel Forschung Drug Research. Oct 48(10): 1033-1036.

The maintenance of double-blind conditions in placebo-controlled trials depends on the quality of the placebo preparation. The placebo should match the active substance-containing preparation as closely as possible, but it must not contain any substances that might themselves be pharmacologically active. Active substances characterized by a particular colour taste, smell or other easily perceptible properties constitute a challenge to researchers. The way of developing a placebo that matches a phytopharmaceutical to a satisfactory extent is described and discussed.

Ellison, J. M. (1998). Antidepressant-induced sexual dysfunction: Review, classification, and suggestions for treatment. Harvard Review Of Psychiatry. Nov Dec 6(4): 177-189.

Sexual function, an important component of quality of life, is often affected by antidepressant treatment. Reports associate antidepressant medications with a wide range of sexual disorders of desire, arousal, and orgasm, and with the occurrence of sexual pain. Fewer sexual dysfunctions have been reported with bupropion, nefazodone, and mirtazapine than with the monoamine-oxidase inhibitors, tricyclic antidepressants, selective serotonin-reuptake inhibitors, and venlafaxine. Sexual dysfunctions may occur in more than half of patients treated with selective serotonin-reuptake inhibitors, but patients may not readily divulge sexual information unless a clinician is knowledgeable and proactive in assessment. Once an antidepressant-induced sexual dysfunction is detected and its nature is characterized, an appropriate treatment intervention can be chosen in order to alleviate the sexual disorder and enhance treatment compliance. This review classifies antidepressant-induced sexual dysfunctions, discusses assessment and differential diagnosis, and describes currently reported treatment approaches.

Yang, X. and Z. L. Li (1998). Callus formation in relation to changes of the membrane Ca2+ in the graft unions of Ginkgo biloba L. Chinese Science Bulletin. Oct 43(20): 1732-1736.

The relationship between the callus formation and intracellular Ca2+ at the early stage of development of graft unions in Ginkgo biloba L. was investigated. On the second day after grafting, part of the undamaged living cells at the graft interface of the stock and scion in the regions of the cortex and. pith began to dedifferentiate or divide. 8 d after grafting, a great number of callus cells were produced from the cortex and phloem, while callus bridges linking the stock with scion formed between the callus cells of the graft partners from the cortex. A membrane Ca2+ probe, chlortetracycline (CTC), was used to locate the intracellular Ca2+ distribution and it was found that the cortical and pith parenchyma cells were the first to show remarkably increased CTC-Ca2+ fluorescence, suggesting that the cortical and other parenchyma cells play a leading role at the early stage of development of graft unions by earlier dedifferentiation and more rapid production of callus cells.

Simonson, W. (1998). Promising agents for treating Alzheimer's disease. American Journal Of Health System Pharmacy. Nov 1(55): S11-S16.

Key issues related to the pharmacotherapy of Alzheimer's disease (AD) are discussed, and current and investigational agents are described.There are three key issues in the pharmacotherapy of AD. First, there is a need to eliminate or minimize drug-related adverse reactions. Second, concurrent diseases that either resemble AD or complicate its treatment must be addressed. The third issue is the need for pharmacotherapy not only to improve cognitive performance but to treat related symptoms. Current strategies for treating AD usually rely on increasing cholinergic function. To date, cholinesterase inhibitors (ChEIs) are the only agents that have been well studied and that have shown efficacy by improving cognitive deficits and, in some cases, psychiatric and behavioral components of AD. Tacrine is rarely used today; the only other FDA-approved ChEI is donepezil. Many other approaches are under clinical investigation, including selective muscarinic agonists, antioxidants, anti-inflammatory drugs, and estrogen replacement therapy. New drug discovery efforts focus on molecular events believed to be important in the pathogenesis of AD. Future pharmacotherapy will probably involve increased use of ChEIs in combination with drugs that have other mechanisms of action.Current treatment of AD primarily involves ChEI therapy, but other therapeutic options, particularly combination therapies, hold promise.

Miller, L. G. (1998). Herbal medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Archives Of Internal Medicine. Nov 158(20): 2200-2211.

Herbal medicinals are being used by an increasing number of patients who typically do not advise their clinicians of concomitant use. Known or potential drug-herb interactions exist and should be screened for. If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used with other known hepatoxic drugs, such as anabolic steroids, amiodarone, methotrexate, and ketoconazole. However, Echinacea lacks the 1,2 saturated necrine ring associated with hepatoxicity of pyrrolizidine alkaloids. Nonsteroidal anti-inflammatory drugs may negate the usefulness of feverfew in the treatment of migraine headaches. Feverfew, garlic, Ginkgo, ginger, and ginseng may alter bleeding time and should not be used concomitantly with warfarin sodium. Additionally, ginseng may cause headache, tremulousness, and manic episodes in patients treated with phenelzine sulfate. Ginseng should also not be used with estrogens or corticosteroids because of possible additive effects. Since the mechanism of action of St John wort is uncertain, concomitant use with monoamine oxidase inhibitors and selective serotonin reuptake inhibitors is ill advised. Valerian should not be used concomitantly with barbiturates because excessive sedation may occur. Kyushin, licorice, plantain, uzara root, hawthorn, and ginseng may interfere with either digoxin pharmacodynamically or with digoxin monitoring. Evening primrose oil and borage should not be used with anticonvulsants because they may lower the seizure threshold. Shankapulshpi, an Ayurvedic preparation, may decrease phenytoin levels as well as diminish drug efficacy. Kava when used with alprazolam has resulted in coma. Immunostimulants (eg, Echinacea and zinc) should not be given with immunosuppressants (eg, corticosteroids and cyclosporine). Tannic acids present in some herbs (eg, St John wort and saw palmetto) may inhibit the absorption of iron. Kelp as a source of iodine may interfere with thyroid replacement therapies. Licorice can offset the pharmacological effect of spironolactone. Numerous herbs (eg, karela and ginseng) may affect blood glucose levels and should not be used in patients with diabetes mellitus.

Mashour, N. H., G. I. Lin, et al. (1998). Herbal medicine for the treatment of cardiovascular disease: Clinical considerations. Archives Of Internal Medicine. Nov 158(20): 2225-2234.

Herbs have been used as medical treatments since the beginning of civilization and some derivatives (eg, aspirin, reserpine, and digitalis) have become mainstays of human pharmacotherapy. For cardiovascular diseases, herbal treatments have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, venous insufficiency, and arrhythmia. However, many herbal remedies used today have not undergone careful scientific assessment, and some have the potential to cause serious toxic effects and major drug-to-drug interactions. With the high prevalence of herbal use in the United States today, clinicians must inquire about such health practices for cardiac disease and be informed about the potential for benefit and harm. Continuing research is necessary to elucidate the pharmacological activities of the many herbal remedies now being used to treat cardiovascular diseases.

Ezzo, J., B. M. Berman, et al. (1998). Complementary medicine and the Cochrane Collaboration. Jama Journal Of The American Medical Association. Nov 280(18): 1628-1630.

Wong, A. H. C., M. Smith, et al. (1998). Herbal remedies in psychiatric practice. Archives Of General Psychiatry. Nov 55(11): 1033-1044.

Patients' use of alternative and complementary health services has created a need for physicians to become informed about the current literature regarding these treatments. Herbal remedies may be encountered in psychiatric practice when they are used to treat psychiatric symptoms; produce changes in mood, thinking, or behavior as a side effect; or interact with psychiatric medications. English-language articles and translated abstracts or articles (where available) found on MEDLINE and sources from the alternative/complementary health field were reviewed. Each herb was assessed for its safety, side effects, drug interactions, and efficacy in treating target symptoms or diagnoses, A synopsis of the information available for each herb is presented. In many cases the quantity and quality of data were insufficient to make definitive conclusions about efficacy or safety. However, there was good evidence for the efficacy of St John's wort for the treatment of depression and for ginkgo in the treatment of memory impairment caused by dementia. More research is required for most of the herbs reviewed, but the information published to date is still of clinical interest in diagnosing, counseling, and treating patients who may be taking botanical remedies.

Zink, T. and J. Chaffin (1998). Herbal 'health' products: What family physicians need to know. American Family Physician. Oct 58(5): 1133-1140.

Patients who self-medicate with herbs for preventive and therapeutic purposes may assume that these products are safe because they are ''natural,'' but some products cause adverse effects or have the potential to interact with prescription medications. The United States lacks a regulatory system for herbal products. Although only limited research on herbs has been published, St John's wort shows promise as a treatment for depression. Ginkgo biloba extract is possibly effective for cerebrovascular insufficiency and dementia. Feverfew is used extensively in Canada for migraine prophylaxis but needs more rigorous study. Ephedrine has been regulated by many states because its misuse has been associated with several deaths. Echinacea is being tried as an agent for immune stimulation, and garlic is under study for cholesterol-lowering properties, but both require more study. Physicians should educate themselves and their patients about the efficacy and adverse interactions of herbal agents and the limitations of our present knowledge of them.

DeLaGarza, V. W. (1998). New drugs for Alzheimer's disease. American Family Physician. Oct 58(5): 1175-1182.

Alzheimer's disease is characterized by degeneration of various structures in the brain, with development of amyloid plaques and neurofibrillary tangles. Deficiencies of acetylcholine and other neurotransmitters also occur. Pharmacologic treatment of the disease generally seeks to correct the histopathology, the biochemical derangements or their effects. The only drugs labeled to date for the treatment of cognitive symptoms in patients with Alzheimer's disease are two cholinesterase inhibitors that prevent the breakdown of acetylcholine in the synapse. Both medications are associated with modest improvements in cognitive function. However, all benefit is lost when these drugs are discontinued; the disease then progresses to the level seen in placebo-treated patients. Tacrine, the first cholinesterase inhibitor to be so labeled, must be taken four times daily and is associated with hepatic toxicity. Donepezil is taken once daily. Side effects of the cholinesterase inhibitors include nausea, vomiting and diarrhea, which tend to subside after the titration period. Other drugs that have shown some promise in the treatment of Alzheimer's disease are vitamin E, estrogen, selegiline and a mixture of ergoloid mesylates. Anti-inflammatory drugs and nicotine are also being studied for their effects as neuroprotectors or neurotransmitter enhancers. The caregivers of patients with Alzheimer's disease may see little effect from these or other investigational agents, but nursing home placement may be delayed.

Roy, S., H. Kobuchi, et al. (1998). Ginkgo biloba extract (EGb 761): antioxidant properties and regulation of gene expression. Ginkgo Biloba Extract Egb 7: 1-17.

EGb 761 has proven beneficial in pathologies related to cerebral and circulatory disorders. Such effects of EGb, 761 extract have been substantiated with placebo-controlled, double-blind clinical trials. Mechanisms underlying the beneficial effects of EGb 761 are only partially understood. One of the main mechanisms seems to be related to the antioxidant properties of EGb 761, which appear to be due to the synergistic action of its major constituents, such as flavonoids, terpenoids and the organic acids. EGb 761 directly scavenges hydroxyl, superoxide, peroxyl and nitric oxide radicals in vitro. EGb 761 also protects against free radical-mediated damage in biological model systems, including ischemia-reperfusion injury of organs and oxidative modification of low-density lipoprotein. EGb 761 inhibits nitric oxide production in macrophages by inhibiting nitric oxide synthase (NOS) activity and regulating inducible-NOS gene expression. EGb 761 down-regulates agonist-induced cell adhesion molecule expression and lymphocyte-endothelial cell adhesion. Exposure of human endothelial cells to EGb 761 resulted in modulation of several mRNA transcripts identified by differential display of mRNA. Such regulatory effects of EGb 761 on nitric oxide metabolism, cell adhesion processes and gene expression may be implicated in its beneficial effect in brain and circulatory disorders.

Perianin, A., S. Rais, et al. (1998). Ginkgolide B (BN 52021) and transductional activities of human polymorphonuclear leukocytes. Ginkgo Biloba Extract Egb 7: 19-31.

Ginkgolide B (GKB, BN 52021), a bioactive component of EGb 761 (a standardized extract of Ginkgo biloba leaves), has been extensively studied as an antagonist of platelet-activating factor (PAF). Although EGb, 761 possesses free radical-scavenger activity due to its flavonoid content, GKB is a potent antioxidant and has pleiotrophic beneficial effects. To gain insight into the mechanism of action of GKB, we explored its potential effects on 2 transductional events, ie, the phospholipase D (PLD) activity of human polymorphonuclear leukocytes (PMN) and protein phosphorylation, and respiratory burst, ie, the production of superoxide anion. PLD cleaves phosphatidylcholine (PC) and generates choline and phosphatidic acid (PA); the latter is then dephosphorylated into diglycerides (DG) by PA-phosphohydrolase (PPH). PLD activity was assessed by 2 methods, one based on radiolabeling PC pools with 1-O-[H-3]octade-cyl-sn-glycero-3-phosphocholine and the other on a chemiluminescence assay for choline,Treatment of radiolabeled PMN with GKB (0.12-7.1 mu M) for 10 min induced a concentration-dependent increase in [H-3]PA formation that was maximal in the presence of 1.2 mu M (approximately +50% of control values); higher drug concentrations were less effective. Elevated [H-3]PA levels were not due to inhibition of PPH, as GKB did not alter the formation of tritiated DG and PA induced by the chemottractant f-Met-Leu-Phe (fMLP). By contrast, PAF-induced PLD activity was efficiently prevented by GKB (IC50 of approximately 1 mu M), which is consistent with its 'anti-PAF' effect. Further evidence of PLD activation by GKB was that the choline content increased in parallel with [H-3]PA levels.GKB (1.2-12 mu M) also stimulated phosphorylation of several proteins (molecular masses of 38, 47, 55 and 67 kDa) in a PMN cytosolic fraction in the presence of [P-32-gamma]ATP. In contrast, when protein phosphorylation was stimulated by protein kinase C (PKC), high GKB concentrations (7.2 and 12.5 mu M) were inhibitory. Stimulation of the PMN respiratory burst by the bacterial peptide fMLP, phorbol myristate acetate or zymosan particles under optimal conditions was not altered by GKB (0.12-7.1 mu M). In contrast, GKB potentiated the respiratory burst induced by the calcium ionophore A23187, whereas that induced by PAF (IC50 of 1 mu M) was inhibited. These data provide evidence that GKB stimulates PLD activity and protein phosphorylation, and suggest that it may have the potential to enhance cellular activities.

Gozin, A., L. DaCosta, et al. (1998). Oxygen radicals activate neutrophil adhesion to and tyrosine phosphorylation in endothelial cells: effect of the antioxidant Ginkgo biloba extract (EGb 761). Ginkgo Biloba Extract Egb 7: 33-43.

Reactive oxygen species (ROS) play an important role in the initiation, duration and breakdown of inflammation, during which polymorphonuclear neutrophils (PMN) are recruited in tissues acid activated. Among inflammatory diseases, ischemia-reperfusion syndrome is an example of an excess of oxygen free radicals produced by PMN NADPH oxidase or by other oxidases, such as xanthine oxidase, which could then be responsible for the important PMN infiltration into tissues.In this study, we looked for the role of ROS in the adhesion of neutrophils to endothelial cells and for the intracellular mechanism involved. Human umbilical cord vein endothelial cells (HUVEC) in culture were subjected to the action of H2O2 and O-2(-), produced by the oxidation of hypoxanthine (HX, 2 x 10(-4) M) by xanthine oxidase (XO, 4.5 mU/ml), and the adhesion of resting PMN was measured by the amount of myeloperoxidase. Adhesion was increased when HUVEC were stimulated for 15 min (from 10 to 22%) and was inhibited by 100 and 200 mu g/ml of Ginkgo biloba extract (EGb, 761), suggesting an involvement of ROS in this increased adhesion.The tyrosine kinase inhibitors genistein (30 mu M), herbimycin A (0.9 mu.M) and erbstatin (26 nM) inhibited this adhesion, suggesting a role for tyrosine kinases in this function. Tyrosine phosphorylation of 2 main bands of 120 and 70 kDa was increased by ROS and inhibited by EGb 761. These bands have been identified as focal adhesion kinase (p125(FAK)), paxillin (PAX) and p130cas, which are cytoskeletal proteins involved in focal adhesion,In conclusion, ROS are involved in an increase of PMN-HUVEC adhesion and tyrosine kinase activation, which leads to paxillin and p130cas phosphorylation. These results support the idea that a correlation may exist between tyrosine phosphorylation and PMN adhesion induced by ROS, but this remains to be confirmed. The production of ROS by PMN could thus be involved in the recruitment of neutrophils into inflamed tissues by increasing their adherence to the vascular endothelium, EGb 761 is able to inhibit the phosphorylation, which seems to be involved early in the mechanism of PMN-HUVEC adhesion. These results confirm the anti-inflammatory properties of EGb 761.

Maixent, J. M., S. Pierre, et al. (1998). Protective effects of Ginkgo biloba extract (EGb 761) on the alterations of Na/K-ATPase isoenzyme activities during cerebral ischemia in mouse. Ginkgo Biloba Extract Egb 7: 45-55.

We investigated the effect of cerebral ischemia and the protection provided by pretreatment with EGb 761 on Na/K-ATPase activity and its isoforms in the mouse. Infarct size, fatty-acid and malondialdehyde contents were evaluated in parallel. Focal ischemia reduced the Na/K-ATPase activity by 43 and 62%, 1 and 6 h postocclusion, respectively. These deleterious effects of ischemia on Na/K-ATPase were prevented by EGb 761 pretreatment. Membrane integrity, as assessed by detergent treatment of isolated membranes, was altered by ischemia, since impermeable vesicles were undetectable. Membrane integrity was intact in preparations from animals pretreated with EGb 761. The activities of isoenzymes, as determined by ouabain in dose-response curves, were all affected by ischemia and preserved by EGb 761. The degree of protection afforded by EGb 761 pretreatment paralleled that of the reduction of enhanced lipid peroxidation of cerebral tissue, as estimated from malondialdehyde production. Because these effects occurred without major changes of overall fatty-acid composition and membrane protein expression of alpha and beta Na/K-ATPase isoforms, and with negligible reduction of the necrotic area, the present results suggest that the decreased intrinsic activity of Na/K-ATPase following hours of cerebral ischemia occurred through mechanisms affecting the membrane microenvironment and enzyme turnover of the 3 active Na/K-ATPase isoenzymes. Through its anti-ischemic effect, EGb 761 might play a crucial role in this neuroprotection.

LeiningerMuller, B., C. Jolivalt, et al. (1998). Oxidation of human apolipoprotein E: isoform susceptibility and protection with Ginkgo biloba extract (EGb 761). Ginkgo Biloba Extract Egb 7: 57-68.

Apolipoprotein E (ApoE) is a polymorphic protein whose specific isoform, ApoE4, has been widely associated with Alzheimer's disease (AD). ApoE may be Linked with this disease by its isoform-specific interaction with lipids or proteins of amyloid plaques. On the other hand, oxidative stress has been proposed to be linked to the development of AD. We recently detected myeloperoxidase (MPO), a heme protein known to be implicated in inflammation, in the human brain. in the presence of H2O2 and Cl-, MPO produces hypochlorite that oxidizes proteins.Using the MPO enzymatic system, we now report that the oxidation of the 3 recombinant ApoE isoforms is differential, with ApoE4 being more susceptible than ApoE3, which is itself more susceptible than ApoE2. To study whether the association of oxidized ApoE with lipids could be modified, we prepared well-defined ApoE-phospholipid complexes. The more the isoform was susceptible to oxidation, the more its ability to interact with phospholipids was reduced. The effects of the Ginkgo biloba extract (EGb 761) at concentrations ranging from 100 to 600 mu g/ml, on the oxidation of each ApoE isoform were investigated. We observed 40% relative protection with EGb 761. Moreover, the more the isoform was susceptible to oxidation, the lower the concentration of EGb 761 that was necessary to protect the protein against oxidation. Taken together, these results could explain the strong association of the epsilon 4 allele with AD. The structural alteration of the more oxidizable ApoE4 could lead to inefficient lipid recycling in the brain, a phenomenon implicated in the development of AD that EGb 761 might be able to prevent.

Ramassamy, C., P. Krzywkowski, et al. (1998). Apolipoprotein E, oxidative stress and Ginkgo biloba extract (EGb 761) in Alzheimer's disease. Ginkgo Biloba Extract Egb 7: 69-83.

Apolipoprotein E (ApoE) is a glycoprotein implicated in cholesterol homeostasis and in lipid turnover. Inheritance of the epsilon 4 allele of ApoE has been demonstrated to be a major risk