Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Nutrients. 2021 Nov 19;13(11):4142. doi: 10.3390/nu13114142.
Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats. Our data indicated ML exhibited protective effects as evidenced by ameliorating the rise in serum activities of alanine transaminase, aspartate transaminase and alkaline phosphatase. This was confirmed histologically as ML prevented DOX-induced pathological alteration in liver architecture. Further, ML administration significantly prevented malondialdehyde accumulation, glutathione depletion and superoxide dismutase and catalase exhaustion. Antioxidant action of ML was associated with enhanced expression of the nuclear translocation of NF-E2-related factor 2 (Nrf2) and a lower expression of forkhead box protein O1 (FOXO1). Also, ML showed potent anti-inflammatory activities highlighted by decreased expression of interleukin 6, tumor necrosis factor α and nuclear factor κB (NF-κB). The anti-apoptotic effects of ML were associated with decreased Bax and enhanced Bcl-2 mRNA expression in liver tissues. ML caused a significant up-regulation in the expression of silent information regulator 1 (Sirt-1). Therefore, it can be concluded that ML prevents liver injury caused by DOX. This could partially be due to the ML regulatory activities on Sirt-1/FOXO1/NF-κB axis.
多柔比星（DOX）是一种常见的化疗药物，具有严重的不良反应，包括肝毒性。苦参酮（ML）是一种具有良好生物活性的吉马烷倍半萜烯。本研究旨在评估 ML 对 DOX 诱导的大鼠肝毒性的保护作用。我们的数据表明，ML 表现出保护作用，表现在改善血清丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶活性的升高。组织学上证实 ML 可防止 DOX 诱导的肝结构病理性改变。此外，ML 给药可显著防止丙二醛积累、谷胱甘肽耗竭以及超氧化物歧化酶和过氧化氢酶耗竭。ML 的抗氧化作用与核易位核因子-红细胞 2 相关因子 2（Nrf2）的表达增强和叉头框蛋白 O1（FOXO1）的表达降低有关。此外，ML 还表现出强大的抗炎活性，表现为白细胞介素 6、肿瘤坏死因子-α和核因子 κB（NF-κB）的表达降低。ML 的抗细胞凋亡作用与肝组织中 Bax 的降低和 Bcl-2 mRNA 表达的增强有关。ML 可显著上调沉默信息调节因子 1（Sirt-1）的表达。因此，可以得出结论，ML 可预防 DOX 引起的肝损伤。这可能部分归因于 ML 对 Sirt-1/FOXO1/NF-κB 轴的调节作用。
