ChemInform Abstract: Chemistry and Biology of Alkylphenols from Ginkgo biloba L.

Jaggy, H.; Koch, E

doi:10.1002/chin.199803275

Cited by 15 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ginkgolic acids and alkylphenols) (Fig. (189)) [1447][1448][1449][1450][1451]. The latter have been associated with adverse events such as allergy, induction of neurons, genotoxicity and other toxicities [1451][1452][1453][1454][1455].…”

Section: Ginkgomentioning

confidence: 99%

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

Zhou¹,

Zhou²,

Liu³

et al. 2009

CMC

149

View full text Add to dashboard Cite

Cytochrome P450 2C9 (CYP2C9) is one of the most abundant CYP enzymes in the human liver. CYP2C9 metabolizes more than 100 therapeutic drugs, including tolbutamide, glyburide, diclofenac, celecoxib, torasemide, phenytoin losartan, and S-warfarin). Some natural and herbal compounds are also metabolized by CYP2C9, probably leading to the formation of toxic metabolites. CYP2C9 also plays a role in the metabolism of several endogenous compounds such as steroids, melatonin, retinoids and arachidonic acid. Many CYP2C9 substrates are weak acids, but CYP2C9 also has the capacity to metabolise neutral, highly lipophilic compounds. A number of ligand-based and homology models of CYP2C9 have been reported and this has provided insights into the binding of ligands to the active site of CYP2C9. Data from the site-directed mutagenesis studies have revealed that a number of residues (e.g. Arg97, Phe110, Val113, Phe114, Arg144, Ser286, Asn289, Asp293 and Phe476) play an important role in ligand binding and determination of substrate specificity. The resolved crystal structures of CYP2C9 have confirmed the importance of these residues in substrate recognition and ligand orientation. CYP2C9 is activated by dapsone and its analogues and R-lansoprazole in a stereo-specific and substrate-dependent manner, probably through binding to the active site and inducing positive cooperativity. CYP2C9 is subject to induction by rifampin, phenobarbital, and dexamethasone, indicating the involvement of pregnane X receptor, constitutive androstane receptor and glucocorticoid receptor in the regulation of CYP2C9. A number of compounds have been found to inhibit CYP2C9 and this may provide an explanation for some clinically important drug interactions. Tienilic acid, suprofen and silybin are mechanism-based inhibitors of CYP2C9. Given the critical role of CYP2C9 in drug metabolism and the presence of polymorphisms, it is important to identify drug candidates as potential substrates, inducer or inhibitors of CYP2C9 in drug development and drug discovery scientists should develop drugs with minimal interactions with this enzyme. Further studies are warranted to explore the molecular determinants for ligand-CYP2C9 binding and the structure-activity relationships.

show abstract

Section: Ginkgomentioning

confidence: 99%

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

Zhou¹,

Zhou²,

Liu³

et al. 2009

CMC

149

View full text Add to dashboard Cite

show abstract

“…Figure 69.3 displays the chemical structure of ginkgotoxin. 24 Ginkgotoxin is not a unique compound in Ginkgo biloba , as this compound also occurs in the paperbark albizia ( Albizia tanganyicensis Baker f.). Analysis of the aqueous extract of ginkgo seeds by liquid chromatography with fl uorescence detection demonstrated a mean free ginkgotoxin concentration of 179 μ g/g and total ginkgotoxin concentration of 308 μ g/g after β -glucosidase treatment.…”

Section: Chemical Compositionmentioning

confidence: 99%

Ginkgo Tree (Ginkgo bilobaL.)

Barceloux

2008

Medical Toxicology of Natural Substances

View full text Add to dashboard Cite

“…The cytotoxic evaluation of bilobol as an antitumor agent is in the preliminary stages. Furthermore, an in-depth investigation into the mechanism and effects of bilobol on its targets has commenced (18)(19)(20). In consideration of previous studies regarding RhoA by our group, the present study aimed to conduct a broader investigation of the anticancer efficacy of bilobol by analyzing its effect on the distribution of RhoA in HepG2 human hepatocellular carcinoma cells.…”

Section: Introductionmentioning

confidence: 99%

Bilobol inhibits the lipopolysaccharide-induced expression and distribution of RhoA in HepG2 human hepatocellular carcinoma cells

Xiaoming

et al. 2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. Recent studies have revealed the localization of RhoA protein in the cell nucleus, in addition to its distribution in the cytosol and cell membrane. The results of previous studies by our group indicated that nuclear RhoA expression is increased, or RhoA is transported into the nucleus, when cells become cancerous or damaged. Furthermore, application of the anticancer agent Taxol appeared to reduce nuclear RhoA localization, indicating an association between the nuclear translocation of RhoA and tumor progression. Bilobol is a traditional Chinese medicine ingredient, however, its anticancer effect has remained unclear. The present study aimed to demonstrate the anticarcinogenic action of bilobol against hepatocellular carcinoma, in order to lay the foundations for subsequent research into the mechanisms underlying its anticancer effects. In the present study, HepG2 cells were treated with lipopolysaccharide (LPS), to induce inflammation, and/or bilobol. By performing an ELISA, it was observed that bilobol was able to suppress the inflammation induced by LPS. In addition, immunofluorescence and western blot analyses indicated that bilobol may reduce the expression of RhoA, suppress translocation of RhoA into the nucleus and inhibit the RhoA/Rho-associated protein kinase signaling pathway. In conclusion, the present study revealed the potential anticancer effects of bilobol.

show abstract

ChemInform Abstract: Chemistry and Biology of Alkylphenols from Ginkgo biloba L.

Cited by 15 publications

References 0 publications

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

Ginkgo Tree (Ginkgo bilobaL.)

Bilobol inhibits the lipopolysaccharide-induced expression and distribution of RhoA in HepG2 human hepatocellular carcinoma cells

Contact Info

Product

Resources

About