Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, China.
Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing, China.
Biomed Pharmacother. 2022 Oct;154:113571. doi: 10.1016/j.biopha.2022.113571. Epub 2022 Aug 22.
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.
溃疡性结肠炎（UC）是一种慢性复发性肠道炎症性疾病。肠道菌群失调，尤其是兼性厌氧肠杆菌科的扩张，可能是 UC 的主要发病机制。葛根芩连汤（GD）是《伤寒论》中记载的一种中药方剂，常用于治疗 UC，并已显示出诱导疾病缓解的优异效果。然而，GD 调节肠道微生物群的作用尚未完全阐明。在此，我们研究了 GD 抑制肠杆菌科扩张的潜在作用，并进一步探讨了这种作用的潜在机制。我们的研究表明，GD 可显著减轻结肠炎小鼠的体重减轻、结肠缩短和结肠炎症。过氧化物酶体增殖物激活受体-γ（PPAR-γ）信号在结肠炎结肠组织中失活，DSS 处理后结肠内容物中大肠杆菌（Escherichia coli，肠杆菌科）的丰度和结肠组织中脂多糖（LPS）的浓度显著升高。值得注意的是，GD 给药可导致 PPAR-γ 激活和 iNOS 失活，从而导致硝酸盐减少、大肠杆菌抑制和 LPS 产生减少。GD 与 PPAR-γ 拮抗剂联合使用，GD 治疗 UC 的效果减弱，对肠杆菌科扩张的抑制作用无效。因此，GD 通过通过激活 PPAR-γ 信号降低腔中硝酸盐水平来预防潜在致病性大肠杆菌的生态失调性扩张，从而改善 UC。
