The Antiemetic Effect of Xiao-Ban-Xia-Tang Formula against Cisplatin-Induced Emesis is Mediated through Inhibition of NLRP3 Inflammasome Activation in a Rat Pica Model

Abstract

Xiao-Ban-Xia-Tang (XBXT), a traditional Chinese medicine formula, has been used for the treatment of emesis for nearly 2000 years, but its underlying mechanism is not yet fully clarified. The purpose of this study is to reveal the antiemetic mechanisms of XBXT by focusing on the NLRP3 inflammasome pathway in a chemotherapy-induced rat pica model. The pica model was generated by a single intraperitoneal injection of cisplatin in this study. Consumption of kaolin (a type of clay) and food and body weight were recorded every 24 hours. Cisplatin-induced increase in kaolin consumption (pica) was used to quantify chemotherapy-induced nausea and vomiting (CINV). Tissue from the ileum and antrum was stained with hematoxylin eosin (HE) to observe pathological changes. The levels of reactive oxygen species (ROS) and inflammatory cytokines, including IL-1β and IL-18 in serum, were detected by ELISA. In addition, changes in the NLRP3 inflammasome activation in the ileum and antrum were investigated using western blot and immunofluorescence microscopy. The results showed that oral administration of XBXT and ondansetron inhibited acute and delayed pica and significantly protected against the gastrointestinal pathological injury induced by cisplatin. The levels of ROS, IL-1β, and IL-18 in the serum of cisplatin-treated rats were also remarkably decreased by XBXT and ondansetron. Moreover, we found that XBXT can inhibit cisplatin-induced NLRP3 inflammasome activation. The present study indicates that the inhibition of the NLRP3 inflammasome activation might be one of the potential mechanisms for the therapeutic effects of XBXT against CINV.