Xiao-Ban-Xia decoction mitigates cisplatin-induced emesis via restoring PINK1/Parkin mediated mitophagy deficiency in a rat pica model

• Published in: Journal of ethnopharmacology 2024-01, Vol.318, p.116882-116882, Article 116882
• Main Authors: Zhao, Yaozhong, Han, Jinyuan, Hu, Wanting, Dai, Yongzhao, Wu, Xipei, Liao, Xiuxiu, Zhou, Haisong, Nie, Ke
• Format: Article
• Language: English
• Subjects: Chemotherapy-induced nausea and vomiting; Gastrointestinal inflammation; Mitophagy; Rat; Xiao-Ban-Xia decoction
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2023.116882

As a traditional Chinese anti-emetic formula, Xiao-Ban-Xia decoction (XBXD) was recorded in Golden Chamber, and has promising anti-emetic effect on chemotherapy-induced nausea and vomiting (CINV). This study aimed to determine whether the underlying mechanism of XBXD against CINV is correlated to the restoration of cisplatin-induced PINK1/Parkin mediated mitophagy deficiency and mitigation of gastrointestinal inflammation. The rat pica model was established by intraperitoneal injection of cisplatin 6 mg/kg. The daily kaolin consumption, food intake and body weight were recorded every 24 h. The pathological damage of gastric antrum and ileum were observed by hematoxylin-eosin staining. The levels of serum reactive oxygen species (ROS), interleukin-1β (IL-1β) and interleukin-1β (IL-18) were detected by ELISA. The expression of microtubule-associated protein 1 light chain 3 (LC3) in gastric antrum and ileum was detected by Immunofluorescence staining. The levels of LC3II, P62/SQSTM1, PTEN-induced putative protein kinases (PINK1), E3 ubiquitin ligase (Parkin), AMP-dependent protein kinases (AMPK), phosphorylated AMPK (p-AMPK), nuclear factor erythroid 2-related factor (Nrf2) and kelch like ECH Associated Protein 1 (Keap1) in gastric antrum and ileum were assayed by western blotting. At 24 h and 72 h following cisplatin challenge, XBXD inhibited cisplatin-induced elevation of kaolin consumption, and improved the daily food intake and body weight loss in rats. Cisplatin-induced gastrointestinal histopathological damages were alleviated, and serum levels of ROS, IL-1β and IL-18 increases were mitigated following XBXD treatments. In gastric antrum and ileum, XBXD activated AMPK-Nrf2 signaling pathway and restored cisplatin-induced PINK1/Parkin mediated mitophagy deficiency. XBXD significantly ameliorated CINV in a cisplatin-induced rat pica model. The underlying anti-emetic mechanism of XBXD might be related to the activation of AMPK-Nrf2 signaling pathway and the restoration of cisplatin-induced PINK1/Parkin-mediated mitophagy deficiency in the gastrointestinal tract. [Display omitted] •XBXD alleviated cisplatin-induced emesis, anorexia and body weight loss.•XBXD alleviated cisplatin-induced gastrointestinal histopathological damages.•XBXD mitigated gastrointestinal damages via restoring mitophagy deficiency.•XBXD activated AMPK-Nrf2 pathway to repair PINK1/Parkin mediated mitophagy.