Yiyi Fuzi Baijiang Decoction Alleviates Ulcerative Colitis Partly by Regulating TLR4-Mediated PI3K/Akt and NF-κB Pathways.

Abstract

Yiyi Fuzi Baijiang Decoction (YFBD), an ancient prescription developed by the ancient Chinese physician, Zhang Zhongjing, has shown remarkable effects in treating ulcerative colitis (UC). However, there are few studies on its mechanism. This study was designed to explore the potential mechanism of YFBD in treating UC. The principal ingredients of YFBD were analyzed using high-performance liquid chromatography (HPLC). Dextran sulfate sodium- (DSS-) induced mice and lipopolysaccharide- (LPS-) stimulated RAW264.7 cells were used in the study. The body weight and disease activity index (DAI) of mice were recorded and analyzed for 10 days. After sacrifice, the colonic tissues were harvested. The colon length was measured, and the histopathological changes were observed by hematoxylin and eosin staining. The levels of inflammatory cytokines in mice colons and RAW246.7 cells were determined by real-time quantitative PCR and immunofluorescence. The effects of YFBD on the TLR4-mediated PI3K/Akt and NF-κB pathways were determined by western blot analysis. HPLC identified five compounds in YFBD: chlorogenic acid, caffeic acid, benzoylmesaconine, benzoyl aconitine, and quercetin. YFBD alleviated weight loss, colon shortening, and colonic histopathological lesion in mice. Meanwhile, it decreased the DAI and histological score of mice with UC. In addition, YFBD remarkably decreased the levels of interleukin- (IL-) 6, IL-1β, and tumor necrosis factor (TNF)-α in the colons of DSS-induced mice and LPS-stimulated RAW246.7 cells. Furthermore, the expression of key proteins in TLR4-mediated PI3K/Akt and NF-κB pathways significantly decreased with YFBD treatment. In conclusion, YFBD had protective effects on mice with UC, which was in part related to its anti-inflammatory effects and downregulation of TLR4-mediated PI3K/Akt and NF-κB pathways.