Limonin ameliorates cisplatin-induced acute liver injury by inhibiting 11β-hydroxysteroid dehydrogenase type 1

作者：Xiang, Yadie; Zhou, Xianke; Zhou, Hong; Li, Dier; Zhong, Menghua; Hong, Xue; Song, Dongyan; Long, Yinyi; Zeng, Xi; Chen, Yudan; Zhou, Jiayi; Liang, Dongning; Fu, Haiyan^*

来源：Biomedicine and Pharmacotherapy, 2023, 168: 115680.

DOI：10.1016/j.biopha.2023.115680

• Limonin
• Cisplatin
• Acute liver injury
• 11 beta-HSD1
• Corticosterone
• Metabolomics

Background: Acute liver injury (ALI) is a common side effect of cisplatin treatment in the clinic and can lead to liver failure if not treated promptly. Previous studies have revealed that Limonin, a critical bioactive substance in citrus fruits, can protect multiple organs from various medical conditions. However, whether Limonin could ameliorate cisplatin-induced ALI remains unclear.Methods: In vivo and in vitro models were induced by cisplatin in the present study. Non-targeted metabolomics was employed to analyze the metabolic changes in the liver after ALI. In addition, molecular docking was utilized to predict the potential targets of Limonin. Results: Limonin attenuated hepatic histopathological injury by reducing hepatocyte apoptosis, lipid peroxidation, and inflammation in cisplatin-challenged mice. Employing metabolomics, we revealed that Limonin mediated the balance of various disturbed metabolic pathways in the liver after cisplatin-induced ALI. Integrating public data mining, molecular docking studies, and in vitro experiments demonstrated that Limonin suppressed the expression and activity of its direct target, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), in the liver, thus reducing the production of corticosterone (CORT), a key metabolite promoted hepatocyte apoptosis. Conclusions: Limonin improves the liver metabolic microenvironment by inhibiting 11 beta-HSD1 to protect against cisplatin-induced ALI.

• 单位
  南方医科大学