结肠炎
炎症性肠病
肠杆菌科
脂多糖
失调
炎症
下调和上调
化学
发病机制
药理学
过氧化物酶体增殖物激活受体
大肠杆菌
微生物学
肠道菌群
受体
免疫学
医学
内科学
生物
生物化学
基因
疾病
作者
Jingyi Hu,Yiheng Tong,Shen Zheng,Yanan Li,Cheng Cheng,Ryan Au,Feng Xu,Yajun Liu,Lei Zhu,Hong Shen
标识
DOI:10.1016/j.biopha.2022.113571
摘要
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disease of the intestine. Dysbiosis, especially the expansion of facultative anaerobic Enterobacteriaceae, maybe the main pathogenesis of UC. Gegen Qinlian decoction (GD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun, is commonly used to treat UC and has shown an excellent effect on inducing disease remission. However, the role of GD in regulating gut microbiota has not been fully clarified. Herein, we investigated the potential effect of GD on inhibiting the expansion of Enterobacteriaceae and further explored the potential mechanism of this action. Our study demonstrated that GD remarkably reduced body weight loss of colitis mice, shortening of colon length, and inflammation of the colon. Peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling was inactivated in colitis colon tissue, and the abundance of Escherichia coli (E. coli, family of Enterobacteriaceae) in colonic contents and the concentration of lipopolysaccharide (LPS) in colonic tissue were significantly upregulated after DSS-treatment. Notably, GD administration can result in the activation of PPAR-γ and inactivation of iNOS, which lead to the reduction of nitrate, the inhibition of E. coli, and less production of LPS. Combined GD with PPAR-γ antagonist, the effect of GD on the treatment of UC was weakened, and effectless in inhibiting the expansion of Enterobacteriaceae. Therefore, GD ameliorates UC by preventing a dysbiotic expansion of potentially pathogenic E. coli by reducing nitrate levels in the lumen through activating PPAR-γ signaling.
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