Ginkgolide A contributes to the potentiation of acetaminophen toxicity by Ginkgo biloba extract in primary cultures of rat hepatocytes

Background: The official compendium of the quantification of ginkgo flavonoids from Ginkgo biloba extract has been proposed using HPLC. The drawbacks of this technique appear to be due to the restricted efficiency in terms of the recovery results and suitability of the system for the quantification of these compounds. This study investigated the potential advantages and limitations of the development of efficient extraction methods for the recovery of flavonol glycosides (quercetin, kaempferol and isorhamnetin) and terpene trilactones (bilobalide, ginkgolide A, ginkgolide B and ginkgolide C) using extraction, quantification and detection techniques, namely, GC-FID and UHPLC-DAD, which are alternatives to those techniques available in the literature. Methods: Two different extraction methodologies have been developed for the determination of flavonoids (quercetin, kaempferol and isorhamnetin) and terpene trilactones (bilobalide, ginkgolide A, ginkgolide B and ginkgolide C) using ultra-high-pressure liquid chromatography coupled to a diode array detector and gas chromatography coupled to a flame ionization detector. Results: In this study, the Ginkgo biloba extract mass, hydrolysis preparation method (with or without reflux), and volume of the extraction solution seemed to affect the ginkgo flavonoid recovery. The UHPLC-based method exhibited higher extraction efficiency for ginkgo flavonoid quantification compared to the pharmacopoeial method. The developed method exhibited higher extraction efficiency for terpene quantification compared to the previous method that used extractive solution without pH adjustment, with less time of extraction and less amount of the sample and organic solvent aliquots. Conclusion: The UHPLC and GC analysis methods established in this study are both effective and efficient. These methods may improve the quality control procedures for ginkgo extract and commercial products available in today´s natural health product market. The results indicate that redeveloped extraction methods can be a viable alternative to traditional extraction methods.

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Current Perspectives on the Beneficial Role of Ginkgo biloba in Neurological and Cerebrovascular Disorders

Integrative Medicine Insights ◽

10.4137/imi.s25054 ◽

2015 ◽

Vol 10 ◽

pp. IMI.S25054 ◽

Cited By ~ 52

Author(s):

Kevin M. Nash ◽

Zahoor A. Shah

Keyword(s):

Ginkgo Biloba ◽

Clinical Investigation ◽

Cerebrovascular Disorders ◽

Cerebrovascular Diseases ◽

Ginkgo Biloba Extract ◽

Glutamate Excitotoxicity ◽

Egb 761 ◽

Ginkgolide A ◽

Therapeutic Mechanisms ◽

The Individual

Ginkgo biloba extract is an alternative medicine available as a standardized formulation, EGb 761®, which consists of ginkgolides, bilobalide, and flavonoids. The individual constituents have varying therapeutic mechanisms that contribute to the pharmacological activity of the extract as a whole. Recent studies show anxiolytic properties of ginkgolide A, migraine with aura treatment by ginkgolide B, a reduction in ischemia-induced glutamate excitotoxicity by bilobalide, and an alternative antihypertensive property of quercetin, among others. These findings have been observed in EGb 761 as well and have led to clinical investigation into its use as a therapeutic for conditions such as cognition, dementia, cardiovascular, and cerebrovascular diseases. This review explores the therapeutic mechanisms of the individual EGb 761 constituents to explain the pharmacology as a whole and its clinical application to cardiovascular and neurological disorders, in particular ischemic stroke.

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Effect of Ginkgo biloba extract on oxidative metabolism of valproic acid in hepatic microsomes from donors with the CYP2C91/1 genotypeThis article is one of a selection of papers published in this special issue (part 1 of 2) on the Safety and Efficacy of Natural Health Products.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y06-085 ◽

2007 ◽

Vol 85 (9) ◽

pp. 848-855 ◽

Cited By ~ 11

Author(s):

Andrew M. Numa ◽

Frank S. Abbott ◽

Thomas K.H. Chang

Keyword(s):

Valproic Acid ◽

Ginkgo Biloba ◽

Oxidative Metabolism ◽

Ginkgo Biloba Extract ◽

Natural Health Products ◽

Natural Health ◽

Hepatic Microsomes ◽

Ginkgolide A ◽

Health Products ◽

Ginkgo Biloba Extracts

We investigated the effect of Ginkgo biloba extracts and some of its individual constituents on the oxidative metabolism of valproic acid (VPA) in hepatic microsomes from donors with the CYP2C9*1/*1 genotype. G. biloba extract decreased 4-ene-VPA, 3-OH-VPA, 4-OH-VPA, and 5-OH-VPA formation with mean (± SE) IC50 values of 340 ± 40 μg/mL, 370 ± 100 μg/mL, 180 ± 30 μg/mL, and 210 ± 20 μg/mL, respectively. This was associated with inhibition of not only CYP2C9*1, but also CYP2A6 and CYP2B6. Bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, quercetin-3-O-rutinoside, kaempferol-3-O-rutinoside, and isorhamnetin-3-O-rutinoside were not responsible for the inhibition of VPA metabolism by the extract. When analyzed as the sum of the aglycone and total glycosides present in the extract, quercetin decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 76%, 51%, and 70%, respectively, kaempferol decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 65%, 46%, and 49%, respectively, and isorhamnetin decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 29%, 26%, and 31%, respectively. The 3 aglycones did not affect 3-OH-VPA formation. In summary, G. biloba extract decreased hepatic microsomal formation of 4-ene-VPA, 4-OH-VPA, 5-OH-VPA, and 3-OH-VPA, but the effect was not due to the terpene trilactones or flavonol glycosides investigated in our study.

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