Diosbulbin B (DIOB) is an effective component of air potato yam with antitumor and anti-inflammatory activities, and it is the main toxic component leading to hepatotoxicity. However, the mechanism of its hepatotoxicity remains unclear. In this study, we aimed to systematically elucidate the molecular action of DIOB on liver metabolic function through systems toxicology approaches. C57BL/6 mice were orally treated with DIOB (10, 30, 60 mg/kg) for 28 days, and the liver metabonomics and histopathology, molecular docking, mRNA expression levels, and activities of enzymes were analyzed. The results illustrated that DIOB could affect fatty acid and glucose metabolism, block the TCA cycle, and DIOB also could disorder bile acid synthesis and transport and promote the occurrence of hyperbilirubinemia. In addition, DIOB increased Cyp3a11 expression in a dose-dependent manner. Thus, these results provide new insights into the mechanism of hepatotoxicity caused by DIOB.

中文翻译：

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系统毒理学方法揭示了薯DiB诱导的雄性小鼠肝毒性的机制。

薯bulB（DIOB）是马铃薯薯类的有效成分，具有抗肿瘤和抗炎作用，是导致肝毒性的主要毒性成分。然而，其肝毒性的机制仍不清楚。在这项研究中，我们旨在通过系统毒理学方法系统地阐明DIOB对肝脏代谢功能的分子作用。用DIOB（10、30、60 mg / kg）口服治疗C57BL / 6小鼠28天，并分析了肝脏的代谢组学和组织病理学，分子对接，mRNA表达水平以及酶的活性。结果表明，DIOB可能影响脂肪酸和葡萄糖的代谢，阻断TCA循环，并且DIOB也可能使胆汁酸的合成和运输紊乱，并促进高胆红素血症的发生。此外，DIOB以剂量依赖性方式增加Cyp3a11表达。因此，这些结果为DIOB引起的肝毒性机制提供了新的见解。