Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from the unripe fruit of Evodia rutaecarpa, is used to treat hypertension, postpartum hemorrhage, dysentery, and amenorrhea as a traditional medicine in Asia. We investigated the effect of rutaecarpine on acetaminophen-induced hepatotoxicity in mice. Rutaecarpine was administered orally daily for seven consecutive days, followed by intraperitoneal injection of acetaminophen in mice on day seven to induce hepatotoxicity. Rutaecarpine pretreatment significantly decreased acetaminophen-induced serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activities and hepatic malondialdehyde content and prevented acetaminophen-induced hepatic glutathione depletion. Furthermore, CYP2E1 expression was decreased by rutaecarpine pretreatment in a dose-dependent manner. Rutaecarpine pretreatment inhibited acetaminophen-induced expression of inflammatory cytokines by inhibiting NF-κB activation by JNK1/2. Also, rutaecarpine pretreatment promoted Nrf2-mediated activation of the antioxidant enzymes GCLC, HO-1, and NQO1. This indicates that the protective effect of rutaecarpine during acetaminophen-induced acute liver injury is mediated by the activation of antioxidant enzymes. Therefore, rutaecarpine has a protective effect of APAP-induced liver damage.

中文翻译：

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芸香碱通过激活抗氧化酶来防止对乙酰氨基酚引起的小鼠急性肝损伤

吴茱萸碱是一种从吴茱萸未成熟果实中分离出来的吲哚并吡啶并喹唑啉酮生物碱，在亚洲作为传统药物用于治疗高血压、产后出血、痢疾和闭经。我们研究了吴茱萸碱对对乙酰氨基酚诱导的小鼠肝毒性的影响。连续七天每天口服吴茱萸碱，然后在第七天给小鼠腹腔注射对乙酰氨基酚以诱导肝毒性。吴茱萸碱预处理显着降低对乙酰氨基酚诱导的血清丙氨酸氨基转移酶（ALT）/天冬氨酸氨基转移酶（AST）活性和肝脏丙二醛含量，并防止对乙酰氨基酚诱导的肝脏谷胱甘肽耗竭。此外，吴茱萸碱预处理以剂量依赖性方式降低 CYP2E1 表达。吴茱萸碱预处理通过抑制 JNK1/2 的 NF-κB 激活来抑制对乙酰氨基酚诱导的炎症细胞因子的表达。此外，吴茱萸碱预处理促进了 Nrf2 介导的抗氧化酶 GCLC、HO-1 和 NQO1 的激活。这表明吴茱萸碱在对乙酰氨基酚诱导的急性肝损伤过程中的保护作用是通过抗氧化酶的激活介导的。因此，吴茱萸碱对APAP所致的肝损伤具有保护作用。