Modified Pulsatillae decoction inhibits DSS-induced ulcerative colitis in vitro and in vivo via IL-6/STAT3 pathway

• Published in: BMC complementary and alternative medicine Vol. 20; no. 1; pp. 1 - 179
• Main Authors: Huangfu, Shaohua, Dou, Renjie, Zhong, Sixia, Guo, Mengjie, Gu, Chunyan, Jurczyszyn, Artur, Yang, Ye, Jiang, Bin
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 09.06.2020; BioMed Central; BMC
• Subjects: Adalimumab; Analysis; Body weight; Colon; Colorectal cancer; Colorectal carcinoma; Complications and side effects; Corticoids; Corticosteroids; Cytokines; Development and progression; Dextran; Dextrans; DSS; Gene expression; Golimumab; Health services; Herbal medicine; House mouse; IL-1β; IL-6/STAT3 pathway; Immunosuppression; Immunosuppressive agents; Immunotherapy; Inflammatory bowel disease; Inflammatory bowel diseases; Injury analysis; Interleukin 6; Medical research; Modified Pulsatillae decoction; NCM460; NF-κB protein; Pathogenesis; Rectum; Side effects; Signal transduction; Sodium sulfate; Stat3 protein; Sulfates; Tumor necrosis factor-TNF; Ulcerative colitis; China
• ISSN: 2662-7671; 2662-7671; 1472-6882
• DOI: 10.1186/s12906-020-02974-9

Background Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon and rectum, which is positively correlated with the occurrence of IBD-related colorectal cancer (IBD-CRC). Conventional therapies based on drugs such as corticosteroids, mesalamine, and immunosuppression have serious side effects. Pulsatillae decoction (PD) served as a classical prescription for the treatment of colitis in China, has been shown to exert prominent curative effects and good safety. Based on clinical experience and our amelioration, we added an extra herb into this classical prescription, but its therapeutic effect on UC and the underlying mechanism are still unclear. Results We first found the curative effect of modified PD on dextran sodium sulfate (DSS)-incubated NCM460 cells. Then C57BL/6 mice were administered DSS to induce UC to evaluate the therapeutic of modified PD. The results showed that modified PD alleviated the inflammatory injury, manifested in body weight, colon length, and disease activity index, with histological analysis of colon injury. Transcriptomic sequencing indicated that modified PD treatment downregulated the IL-6/STAT3 signaling pathway, and reduced the levels of p-NF-κB, IL-1[beta] and NLRP3, which were confirmed by western blot. Conclusions Collectively, our results indict that modified PD could efficiently relieve clinical signs and inflammatory mediators of UC, providing evidence of the anti-colitis effect of modified PD, which might provide novel strategies for therapeutic intervention in UC, which may be applied to the prevention of IBD-CRC. Keywords: Modified Pulsatillae decoction, NCM460, DSS, Ulcerative colitis, IL-6/STAT3 pathway