Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510405, China.
Drug Metab Pharmacokinet. 2023 Jun;50:100507. doi: 10.1016/j.dmpk.2023.100507. Epub 2023 Mar 30.
Diosbulbin B (DIOB) has been reported to cause serious liver injury. However, in traditional medicine, DIOB-containing herbs are highly safe in combination with ferulic acid (FA)-containing herbs, suggesting potential neutralizing effect of FA on the toxicity of DIOB. DIOB can be metabolized to generate reactive metabolites (RMs), which can covalently bind to proteins and lead to hepatoxicity. In the present study, the quantitative method was firstly established for investigating the correlation between DIOB RM-protein adducts (DRPAs) and hepatotoxicity. Then, we estimated the detoxication effect of FA in combination with DIOB and revealed the underlying mechanism. Our data indicated that the content of DRPAs positively correlate with the severity of hepatotoxicity. Meanwhile, FA is able to reduce the metabolic rate of DIOB in vitro. Moreover, FA suppressed the production of DRPAs and decreased the serum alanine/aspartate aminotransferase (ALT/AST) levels elevated by DIOB in vivo. Thus, FA can ameliorate DIOB-induced liver injury through reducing the production of DRPAs.
黄独素 B（DIOB）已被报道可导致严重肝损伤。然而，在传统医学中，含 DIOB 的草药与含阿魏酸（FA）的草药合用非常安全，提示 FA 对 DIOB 的毒性具有潜在的中和作用。DIOB 可代谢生成反应性代谢物（RMs），可与蛋白质共价结合导致肝毒性。在本研究中，首次建立了定量方法来研究 DIOB RM-蛋白质加合物（DRPAs）与肝毒性之间的相关性。然后，我们评估了 FA 与 DIOB 合用的解毒作用，并揭示了其潜在的机制。我们的数据表明，DRPAs 的含量与肝毒性的严重程度呈正相关。同时，FA 能够降低 DIOB 在体外的代谢率。此外，FA 抑制了 DRPAs 的生成，并降低了 DIOB 在体内引起的血清丙氨酸/天冬氨酸转氨酶（ALT/AST）水平升高。因此，FA 可通过减少 DRPAs 的生成来改善 DIOB 诱导的肝损伤。
