Abstract

Air Potato Yam is widely used in the treatment of many conditions such as cancer, inflammation, and goiter. Diosbulbin B (DIOB) is the primary active component of Air Potato Yam, and it exhibits anti-tumor and anti-inflammatory properties. The main purpose of this study was to determine the mechanism by which DIOB induces lung toxicity, using metabonomics and molecular biology techniques. The results showed that the lung toxicity induced by DIOB may occur because of a DIOB-induced increase in the plasma levels of long-chain free fatty acids and endogenous metabolites related to inflammation. In addition, treatment with DIOB increases the expression of the cyp3a13 enzyme, which leads to enhanced toxicity in a dose-dependent manner. The molecular mechanism underlying toxicity in mouse lung cells is the DIOB-mediated inhibition of fatty acid β-oxidation, partial glycolysis, and the TCA cycle, but DIOB treatment can also compensate for the low Adenosine triphosphate (ATP) supply levels by improving the efficiency of the last step of the glycolysis reaction and by increasing the rate of anaerobic glycolysis. Using metabonomics and other methods, we identified the toxic effects of DIOB on the lung and clarified the underlying molecular mechanism.

中文翻译：

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代谢组学方法研究 diosbulbin B 诱导的肺毒性并阐明其在雄性小鼠中的潜在机制

摘要

空气马铃薯山药广泛用于治疗许多疾病，如癌症、炎症和甲状腺肿。Diosbulbin B (DIOB) 是 Air Potato Yam 的主要活性成分，具有抗肿瘤和抗炎特性。本研究的主要目的是利用代谢组学和分子生物学技术确定 DIOB 诱导肺毒性的机制。结果表明，DIOB 引起的肺毒性可能是由于 DIOB 诱导的血浆中长链游离脂肪酸和与炎症相关的内源性代谢物水平升高而发生的。此外，用 DIOB 处理会增加 cyp3a13 酶的表达，从而以剂量依赖性方式导致毒性增强。小鼠肺细胞毒性的分子机制是 DIOB 介导的对脂肪酸 β 氧化、部分糖酵解和 TCA 循环的抑制，但 DIOB 治疗还可以通过提高效率来补偿低三磷酸腺苷 (ATP) 供应水平糖酵解反应的最后一步，并通过增加无氧糖酵解的速率。使用代谢组学和其他方法，我们确定了 DIOB 对肺的毒性作用，并阐明了潜在的分子机制。