School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, China.
School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, China.
J Ethnopharmacol. 2024 Jan 10;318(Pt A):116882. doi: 10.1016/j.jep.2023.116882. Epub 2023 Jul 6.
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.
作为一种传统的中药止吐配方，小半夏汤（XBXD）被记录在《金匮要略》中，对化疗引起的恶心和呕吐（CINV）具有良好的止吐作用。
本研究旨在确定 XBXD 对 CINV 的潜在作用机制是否与恢复顺铂诱导的 PINK1/Parkin 介导的线粒体自噬缺陷和减轻胃肠道炎症有关。
通过腹腔注射顺铂 6mg/kg 建立大鼠嗜食模型。每 24 小时记录一次高岭土消耗量、食物摄入量和体重。通过苏木精-伊红染色观察胃窦和回肠的病理损伤。通过酶联免疫吸附试验检测血清活性氧（ROS）、白细胞介素-1β（IL-1β）和白细胞介素-1β（IL-18）水平。通过免疫荧光染色检测胃窦和回肠中微管相关蛋白 1 轻链 3（LC3）的表达。通过 Western blot 检测胃窦和回肠中 LC3II、P62/SQSTM1、PTEN 诱导的假定蛋白激酶（PINK1）、E3 泛素连接酶（Parkin）、腺苷酸活化蛋白激酶（AMPK）、磷酸化 AMPK（p-AMPK）、核因子红细胞 2 相关因子（Nrf2）和 Kelch 样 ECH 相关蛋白 1（Keap1）的水平。
顺铂攻击后 24 小时和 72 小时，XBXD 抑制了顺铂诱导的高岭土消耗增加，并改善了大鼠的每日食物摄入和体重减轻。XBXD 治疗减轻了顺铂引起的胃肠道组织病理学损伤，并降低了血清 ROS、IL-1β 和 IL-18 水平的升高。在胃窦和回肠中，XBXD 激活了 AMPK-Nrf2 信号通路，并恢复了顺铂诱导的 PINK1/Parkin 介导的线粒体自噬缺陷。
XBXD 显著改善了顺铂诱导的大鼠嗜食模型中的 CINV。XBXD 的潜在止吐机制可能与激活 AMPK-Nrf2 信号通路以及恢复顺铂诱导的 PINK1/Parkin 介导的胃肠道中线粒体自噬缺陷有关。
