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

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-alpha, IL-1I3 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-1I3 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.

Automated summary

The study demonstrated that FTA effectively reversed methotrexate-induced intestinal mucositis in rats by reducing inflammation, maintaining intestinal structure, and modulating levels of inflammatory cytokines and immune cells in the bloodstream.