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  • Title: Intra-herb pharmacokinetics interaction between quercetin and isorhamentin.
    Author: Lan K, He JL, Tian Y, Tan F, Jiang XH, Wang L, Ye LM.
    Journal: Acta Pharmacol Sin; 2008 Nov; 29(11):1376-82. PubMed ID: 18954533.
    Abstract:
    AIM: Quercetin and isorhamnetin are common constituents of some herb extracts, such as extracts of gingko leaves and total flavones of Hippophae rhamnoides L. The intra-herb pharmacokinetics interactions between isorhamnetin and quercetin were investigated in the present study. METHODS: Human MDR1 cDNA transfected MDCKII cells were used to validate whether isorhamnein interacted with P-gp. Caco-2 transport assays and a randomized, 3-way crossover pharmacokinetics study in rats were used to investigate the pharmacokinetics interactions. HPLC was used to determine cell transport samples. The total plasma concentrations of quercetinand isorhamnetin were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) by treatment with beta-glucuronidase and sulfatase. RESULTS: The permeability ratio (absorptive permeability/secretive permeability) of isorhamnetin across human MDR1 cDNA transfected MDCKII cells, Caco-2 cells and wild-type MDCKII cells are 0.25+/-0.02, 0.74+/-0.05, and 1.41+/-0.06, respectively. This result proved the role of P-gp in the cell efflux of isorhamnetin. While co-transporting with each other across Caco-2 cells monolayer, the permeability ratio of isorhamnetin and quercetin increased by 4.3 and 2.2 times. After coadministration with each other to rats, the C(max), AUC(0-72 h), and AUC(0-infinity) of both isorhamnetin and quercetin significantly increased compared with single administration. CONCLUSION: The above results proved intra-herb pharmacokinetics interaction between quercetin and isorhamentin. P-gp might play an important role, whereas other drug efflux pumps, such as multi-drug resistance associate protein 2 and breast cancer resistance protein, might be involved. Accordingly, besides the drug-herb interactions, intra-herb interaction might be brought into view with the wide use of herbal-based remedies.
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