Investigating the antiemetic effect of HWZO and the underlying molecular mechanism of its antiemetic effect. CINV models of rats and cells were constructed using cisplatin and substance P, respectively. The intake of kaolin observed the antiemetic effect of HWZO. Effective cell concentrations of HWZO were screened, and 5-HT3R knockdown and overexpression cell lines were constructed. The expression levels of essential markers related to 5-HT and substance P in serum, ileum, and medulla oblongata of rats, as well as cell models, were determined by ELISA, RT-qPCR, and WB. Results of animal experiments showed that HWZO significantly reduced kaolin intake, increased food-intake and body weight in rats, and simultaneously suppressed the expression of key emetogenic molecular markers in the peripheral and central nervous system ( P < 0.05). In cellular experiments, screening for effective concentrations of HWZO was first performed, and the results showed that high doses had the best effect ( P < 0.05). HWZO treatment decreased 5-HT, SP, and SPR levels while increasing SERT expression in cellular models. Subsequently, 5-HT3R knockdown and overexpression cell lines were constructed, and the expression levels of 5-HT, SP, and other related molecular markers of vomiting after HWZO administration were significantly increased in 5-HT3R overexpression cells ( P < 0.05), while decreased in 5-HT3R knockdown cells ( P < 0.05). HWZO is expected to be an effective and safe adjuvant therapy for the treatment of CINV through a multi-targeted and multi-pathway mechanism of action, especially by modulating the 5-HT3R/SERT and SP/SPR signaling pathways.
Zhang et al. (Thu,) studied this question.