| Summary: | 碩士 === 臺北醫學大學 === 藥學研究所 === 96 === Flavonoids are a subclass of dietary polyphenolic compounds present in fruits, vegetables, and herbal plants and are proposed to promote human health by their antioxidant, antiviral, or anticarcinogenic properties. They are suggested to interact with intestinal transport systems including P-glycoprotein (P-gp). Overexpression of the 170-kDa P-gp has been associated with the multidrug resistance (MDR) of cancer cells. The inhibition of P-gp by herbal constituents may provide a novel approach for reversing multidrug resistance in tumor cells. Using human colorectal adenocarcinoma (HCT15) cells as an in vitro model and fexofenadine as a P-gp substrate, four flavonoid families (flavones, flavonols, flavanols, and isoflavones) were evaluated for their inhibitory effects on P-gp to create a structure-activity relationship (SAR). The in vitro data show that galangin, apigenin, and baicalein possess high inhibitory effect on P-gp activity. We may conclude from our results that the number of hydroxyl groups, dimensional structure, and the hydrophobicity of flavonoids play significant influences on their inhibitory effects. The bioavailability of fexofenadine in the rabbits co-administration with baicalein, which inhibits the efflux pump P-gp, is increased significantly compared with the control. The findings of this study indicate potential flavonoids-drug interactions with P-gp substrates. Furthermore, baicalein could be a useful strategy for the development of potential modulators and a promising reversal agent for overcoming MDR.
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