Effect of Ginkgo biloba extract on rat hepatic microsomal CYP1A activity: role of ginkgolides, bilobalide, and flavonols

2004 ◽  
Vol 82 (1) ◽  
pp. 57-64 ◽  
Author(s):  
I fan Kuo ◽  
Jie Chen ◽  
Thomas K.H Chang
Keyword(s):  
Ginkgo Biloba ◽  
Ginkgo Biloba Extract ◽  
Inhibitory Potency ◽  
Hepatic Microsomes ◽  
Cyp1a Activity ◽  
Ginkgo Biloba Extracts ◽  
The Individual ◽  
Vitro Effect

The present study investigated the in vitro effect of Ginkgo biloba extracts and some of the individual constituents (ginkgolides, bilobalide, and flavonols such as kaempferol, quercetin, isorhamnetin, and their glycosides) on CYP1A-mediated 7-ethoxyresorufin O-dealkylation in hepatic microsomes isolated from rats induced with β-naphthoflavone. G. biloba extract competitively inhibited CYP1A activity, with an apparent Ki value of 1.6 ± 0.4 µg/mL (mean ± SE). At the concentrations present in the G. biloba extracts, ginkgolides A, B, C, and J and bilobalide did not affect CYP1A activity, whereas kaempferol (IC50 = 0.006 ± 0.001 µg/mL, mean ± SE), isorhamnetin (0.007 ± 0.001 µg/mL), and quercetin (0.050 ± 0.003 µg/mL) decreased this activity. The monoglycosides (1 and 10 µg/mL) and diglycosides (10 µg/mL) of kaempferol and quercetin but not those of isorhamnetin also inhibited CYP1A activity. The order of inhibitory potency was kaempferol ~ isorhamnetin > quercetin, and for each of these flavonols the order of potency was aglycone >> monoglycoside > diglycoside. In summary, G. biloba extract competitively inhibited rat hepatic microsomal CYP1A activity, but the effect was not due to ginkgolides A, B, C, or J, bilobalide, kaempferol, quercetin, isorhamnetin, or the respective flavonol monoglycosides or diglycosides.Key words: bilobalide, CYP1A, cytochrome P450, Ginkgo biloba, ginkgolide, flavonol.

Effect of Ginkgo biloba extract on oxidative metabolism of valproic acid in hepatic microsomes from donors with the CYP2C9*1/*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.

2007 ◽  
Vol 85 (9) ◽  
pp. 848-855 ◽  
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.

scholarly journals Ensovibep, a novel trispecific DARPin candidate that protects against SARS-CoV-2 variants

2021 ◽  
Author(s):  
Michael Stumpp
Keyword(s):  
Single Agent ◽  
Standard Of Care ◽  
Cooperative Binding ◽  
Wild Type ◽  
Inhibitory Potency ◽  
Alpha Variant ◽  
The Individual ◽  
Very High ◽  
Comprehensive Study

Abstract SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant to vaccine induced and therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study of ensovibep, the first trispecific clinical DARPin candidate, that can simultaneously engage all three units of the spike protein trimer to potently inhibit ACE2 interaction, as revealed by structural analyses. The cooperative binding of the individual modules enables ensovibep to retain inhibitory potency against all frequent SARS-CoV-2 variants, including Omicron, as of December 2021. Moreover, viral passaging experiments show that ensovibep, when used as a single agent, can prevent development of escape mutations comparably to a cocktail of monoclonal antibodies (mAb). Finally, we demonstrate that the very high in vitro antiviral potency also translates into significant therapeutic protection and reduction of pathogenesis in Roborovski dwarf hamsters infected with either the SARS-CoV-2 wild-type or the Alpha variant. In this model, ensovibep prevents fatality and provides substantial protection equivalent to the standard of care mAb cocktail. These results support further clinical evaluation and indicate that ensovibep could be a valuable alternative to mAb cocktails and other treatments for COVID-19.

scholarly journals ANTIOXIDANT, CYTOTOXICITY, AND STABILITY EVALUATION OF GINKGO BILOBA EXTRACT-BASED MICROEMULSIONS FOR ENHANCED THERAPEUTIC ACTIVITY

2017 ◽  
Vol 10 (8) ◽  
pp. 335 ◽  
Author(s):  
Manisha Singh ◽  
Surya Pratap Singh ◽  
Rachana R
Keyword(s):  
Ginkgo Biloba ◽  
Therapeutic Potential ◽  
Ginkgo Biloba Extract ◽  
In Vitro Cytotoxicity ◽  
Scavenging Activity ◽  
Therapeutic Implications ◽  
Chromatography Analysis ◽  
Ic50 Value ◽  
Cytotoxicity Assessment

Objective: This study is aimed to evaluate the antioxidant (AO) potential, cytotoxicity, and stability of preformulated Ginkgo biloba standard extractmicroemulsion (GBME), to investigate if, it retains the therapeutic potential of EGB761 and remains safe and stable for a longer period.Method and Results: GBME has shown enhanced AO (85.2±0.78%, IC50=31.3±0.45 μg/ml) in comparison to EGB761 (74.1±0.51%,IC50=49.4±0.05 μg/ml) using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay. Similarly, 2,2-diphenyl-1-picryl-hydrazyl-hydrate(DPPH) assay has also shown that AO for GBME (94.6±0.04%, IC50=11.4±1.03 μg/ml) was higher than EGB761 (78.6±1.20%, IC50=34.6±0.81 μg/ml).Further, IC50 value of antiradical unit of GBME was much lesser (ABTS=14.3±1.05 μg/ml and DPPH=17.03±1.8 μg/ml) in comparison to EGB761(ABTS=34.1±1.62 μg/ml and DPPH=37.5±0.08 μg/ml). Equivalently, both, hydrogen peroxide scavenging activity, and nitric oxide activity wereappreciably higher for GBME than the pure extract. The in vitro cytotoxicity assessment showed that GBME is quite safe (98.68±0.76% cell viability) incomparison to EGB761 (83.29±1.02%). Thereafter, these samples were tested for stability by evaluating their AO activity along with high-performanceliquid chromatography analysis, for the major phytocompounds, after 1 year, and results suggested that AO of GBME remained stable while comparingwith the freshly prepared GBME, whereas AO of EGB761 reduced significantly as compared to freshly taken EGB761 extract implying the degradationof phytocompounds supporting decrease in AO activity.Conclusion: Therefore, the observed results suggest that GBME maintained AO and scavenging activity along with enhanced shelf life with no observedtoxicity, which can be explored further for its potential therapeutic implications in various oxidative stress-induced central nervous system disorders.

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