Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, China (H.C., Y.C., D.K., X.C., Y.L.) and Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Japan (H.C., Q.Z., I.T., Y.L.).
Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, China (H.C., Y.C., D.K., X.C., Y.L.) and Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Japan (H.C., Q.Z., I.T., Y.L.)
Drug Metab Dispos. 2021 May;49(5):353-360. doi: 10.1124/dmd.120.000308. Epub 2021 Mar 3.
Literature reports that reduces blood lipid levels; however, the underlying mechanism remains unclear. Blood lipid levels are closely related to the enterohepatic circulation of bile acids, where uptake transporters playing a significant role. extract is commonly used in traditional prescriptions and food supplements in China. We investigated the effects of and its five triterpene acids on bile acid uptake transporters, including intestinal apical sodium-dependent bile acid transporter (ASBT) and hepatic sodium/taurocholate cotransporting polypeptide (NTCP). Triterpene acids were fingerprinted by high-performance liquid chromatography-TripleTOF and quantified by ultraperformance liquid chromatography/tandem mass spectrometry. The inhibitory effect of and its five major representative triterpene acids on ASBT and NTCP was investigated by in vitro assays using oocytes expressing ASBT and NTCP. extract exhibited significant inhibitory effects with half-maximum inhibition constants of 5.89 µg/ml and 14.6 µg/ml for NTCP and ASBT, respectively. Among five triterpene acids, poricoic acid A, poricoic acid B, and polyporenic acid C significantly inhibited NTCP function. Poricoic acid A, poricoic acid B, and dehydrotumulosic acid significantly inhibited ASBT function. The representative triterpene acid, poricoic acid A, was identified as a competitive inhibitor of NTCP with an inhibitory constant of 63.4 ± 18.7 µM. In conclusion, our results indicate that both extract and its major triterpenes are competitive inhibitors of ASBT and NTCP. Accordingly, it was suggested that competitive inhibition of these bile acid transporters is one of the underlying mechanisms for the hypolipidemic effect of SIGNIFICANCE STATEMENT: , a commonly used Chinese herbal medicine and food supplement, demonstrates significantly inhibitory effects on the function of apical sodium-dependent bile acid transporter and sodium/taurocholate cotransporting polypeptide. has potential to reduce the blood lipid through inhibition of these uptake transporters in enterohepatic circulation of bile acid.
文献报道， 可降低血脂水平；然而，其潜在机制尚不清楚。血脂水平与胆汁酸的肠肝循环密切相关，其中摄取转运体起着重要作用。 提取物在中国常用于传统方剂和膳食补充剂。我们研究了 及其五种三萜酸对胆汁酸摄取转运体的影响，包括肠道顶端钠依赖性胆汁酸转运体（ASBT）和肝脏钠/牛磺胆酸盐协同转运蛋白（NTCP）。采用高效液相色谱-三重四极杆和超高效液相色谱/串联质谱法对三萜酸进行指纹图谱分析和定量分析。通过在表达 ASBT 和 NTCP 的卵母细胞中进行体外实验，研究了 及其五种主要代表性三萜酸对 ASBT 和 NTCP 的抑制作用。 提取物对 NTCP 和 ASBT 的半数最大抑制常数分别为 5.89 µg/ml 和 14.6 µg/ml，表现出显著的抑制作用。在五种三萜酸中，多孔菌酸 A、多孔菌酸 B 和多孔菌酸 C 显著抑制 NTCP 功能。多孔菌酸 A、多孔菌酸 B 和去氢土莫酸显著抑制 ASBT 功能。代表性三萜酸多孔菌酸 A 被鉴定为 NTCP 的竞争性抑制剂，抑制常数为 63.4 ± 18.7 µM。综上所述，我们的研究结果表明， 提取物及其主要三萜类化合物均为 ASBT 和 NTCP 的竞争性抑制剂。因此，推测这些胆汁酸转运体的竞争性抑制是 的降血脂作用的潜在机制之一。
