Forsythiaside A alleviates methotrexate-induced intestinal mucositis in rats by modulating the NLRP3 signaling pathways

• Published in: International immunopharmacology 2022-02, Vol.103, p.108466-108466, Article 108466
• Main Authors: Lang, Wuying, Cheng, Min, Zheng, Xin, Zhao, Yongping, Qu, Yunlong, Jia, Zhao, Gong, Haizhou, Ali, Ihsan, Tang, Jingwen, Zhang, Haihua
• Format: Article
• Language: English
• Subjects: Animals; Antimetabolites, Antineoplastic - adverse effects; Body weight; Caspase-1; Drugs, Chinese Herbal - therapeutic use; Enzyme-linked immunosorbent assay; Food intake; Forsythiaside A; Glycosides - therapeutic use; Goblet cells; IL-1β; Immunofluorescence; Inflammation; Interleukin 18; Intestinal Mucosa; Intestinal mucositis; Intestine; Leukocytes; Leukocytes (neutrophilic); Lymphocytes; Male; Metastases; Methotrexate; Methotrexate - adverse effects; Mucosa; Mucositis; Mucositis - chemically induced; Mucositis - drug therapy; Mucositis - pathology; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 signaling pathways; Peripheral blood; Rats; Rats, Sprague-Dawley; Signal Transduction; Signaling; Tumor cells; Tumor necrosis factor-α
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.108466

•Methotrexate (MTX) side effects can cause intestinal mucositis (IM).•Forsythiaside A (FTA) alleviated MTX-induced IM.•FTA might suppress the activation of NLRP3 signaling pathway. Most chemotherapeutic drugs can kill the tumor cells, but also cause a vast damage to body, such as intestinal mucositis (IM). The present study was design to find out the effect of Forsythiaside A (FTA) on chemotherapeutic-induced IM in rats. Briefly, for 3 consecutive days, male Sprague–Dawley rats were treated with 7 mg / kg methotrexate (MTX) to establish IM and simultaneously administered with 40 or 80 mg / kg FTA for 7 days. Our results showed that the final body weight and daily food intake were increased, and the disease activity index was reduced in the MTX group after FTA treatment. The MTX group showed the pathological alterations like the inflammatory cells infiltration, the mucosal layer destruction, glands expansion, intestinal villi structure disorder and goblet cells reduction, while we found that 80 mg / kg FTA treatment displayed evident reversal effects. ELISA further suggested that TNF-α, IL-1β and IL-18 levels in serum in MTX-induced rats were reduced after 80 mg / kg FTA treatment. Moreover, FTA decreased the number of leukocytes, neutrophils and lymphocytes in peripheral blood. Western blot and immunofluorescence results indicated that the expression levels of NLRP3, cleaved caspase 1, cleaved IL-1β and CD68 positive rate were down-regulated in MTX-induced rats after 80 mg / kg FTA intervention. The findings of the current study suggested that FTA effectively inhibited MTX-induced IM in rats by attenuating the activation of the NLRP3 signaling pathways.