School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
J Pharm Biomed Anal. 2019 Oct 25;175:112762. doi: 10.1016/j.jpba.2019.07.010. Epub 2019 Jul 8.
As a triterpene saponin, pedunculoside is one of the most abundant, representative and active components in plants of genus Ilex (Aquifoliaceae). Pedunculoside has been used to treat myocardial ischemia, ameliorate hyperlipidemia and prevent liver injury. In this paper, a systemic in vitro liver microsomes / S9 and intestinal bacteria incubation, and in vivo animal experiment were performed, using LC-Q-TOF/MS analysis and a three-step data processing protocol. As a result, Bifidobacterium adolescentis and Bifidobacterium breve were identified to potentially metabolize pedunculoside among the intestinal bacteria tested. A total of 11 metabolites were found and tentatively identified, with 6 in both microsomal and bacterial incubation systems, and 9 after rats orally administered with pedunculoside. The metabolites detected involving both phase I and phase II metabolism, mainly through deglycosylation (hydrolyzation), dehydrogenation, hydroxylation and conjugation, and some of them underwent more than one-step metabolic reactions. Most of the metabolites have not been reported before. In vitro, liver microsome and intestinal bacteria prefer to metabolize pedunculoside in totally different ways; while in vivo, intestinal tract is the most important site for the metabolism and excretion of pedunculoside, where both intestinal bacteria and the host metabolic enzymes participate in its metabolism and disposition. The importance of intestinal bacteria should be highlighted. This study would contribute to a better understanding of pedunculoside metabolism, which can provide scientific evidence for its pharmacodynamic mechanism research and prove its clinical application.
作为三萜皂苷，杠柳苷是冬青属（冬青科）植物中最丰富、最具代表性和最活跃的成分之一。杠柳苷已被用于治疗心肌缺血、改善高血脂和预防肝损伤。本文通过体外肝微粒体/S9 和肠道细菌孵育以及体内动物实验，采用 LC-Q-TOF/MS 分析和三步数据处理方案，研究了杠柳苷的体内外代谢。结果表明，在所测试的肠道细菌中，青春双歧杆菌和短双歧杆菌可能代谢杠柳苷。共发现并初步鉴定了 11 种代谢物，其中 6 种在微粒体和细菌孵育系统中均有发现，9 种在大鼠灌胃给予杠柳苷后被检测到。这些代谢物涉及 I 相和 II 相代谢，主要通过去糖基化（水解）、脱氢、羟化和结合反应，其中一些经历了不止一步的代谢反应。大多数代谢物以前没有报道过。体外实验表明，肝微粒体和肠道细菌以完全不同的方式代谢杠柳苷；而在体内，肠道是杠柳苷代谢和排泄的最重要部位，肠道细菌和宿主代谢酶都参与了其代谢和处置。肠道细菌的重要性应该得到强调。本研究有助于更好地了解杠柳苷的代谢，为其药效机制研究提供科学依据，并证明其临床应用。
