Pulsatilla chinensis saponins improve SCFAs regulating GPR43-NLRP3 signaling pathway in the treatment of ulcerative colitis. (23rd May 2023)

• Record Type: Journal Article
• Authors: Li, Zexie; Song, Yonggui; Xu, Weize; Chen, Jingbin; Zhou, Rou; Yang, Ming; Zhu, Genhua; Luo, Xiaoquan; Ai, Zhifu; Liu, Yali; Su, Dan
• Is Part Of: Journal of ethnopharmacology. Volume 308(2023)
• Publication Date: 2023-05-23
• Subjects: Pulsatilla chinensis saponins -- Ulcerative colitis -- Pharmacokinetic -- Short-chain fatty acids -- GPR43 protein -- NLRP3 inflammasome; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2023.116215
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Pulsatilla decoction has been extensively used to treat ulcerative colitis (UC) in recent years. Pulsatilla chinensis saponin (PRS), the active ingredient of its monarch medicine Pulsatilla chinensis (Bunge) Regel, plays a crucial role in the treatment of UC, but its specific mechanism of action has not been fully elucidated. Aim of the study: This study aims to investigate the protective effect and possible mechanism of PRS on DSS-induced ulcerative colitis in rats. Materials and methods: In this study, the DSS-induced colitis model was used to explore the metabolism and absorption of PRS under UC, detect the content of short-chain fatty acids (SCFAs) in colon tissue, the expression of receptor G Protein-Coupled Receptor 43 (GPR43) protein and inflammasome NLRP3, and observe the expression level of IL-1β, IL-6 and TNF-α in colon tissue. The protective effect of the PRS was also observed. Results: It was found that in the UC group, the absorption rate and extent of drugs increased, and the elimination was accelerated. Compared with the control group, PRS increased the content of short-chain fatty acids (SCFAs) in colon tissue, promoted the expression of SCFAs receptor GPR43 protein, inhibited the activation of the NLRP3 inflammasome, and decreased the content of IL-1β, IL-6 and TNF-α. PRS protects the colon in DSS-induced inflammatory bowel disease by increasing the content of SCFAs, promoting the expression of GPR43 protein, inhibiting the activation of the NLRP3 inflammasome, and reversing the increase in IL-1β, IL-6 and TNF-α levels. Conclusions: PRS can increase the content of colonic SCFAs, activate the GPR43-NLRP3 signaling pathway, and reduce the levels of pro-inflammatory cytokines, thereby improving the symptoms of DSS-induced colitis. Graphical abstract: Image 1 Highlights: Pharmacokinetic study of five compounds in normal and UC rats after oral administration of PRS. Effects of PRS on Short Chain Fatty Acids in Rat Feces. Effect of PRS on GPR43 and NLRP3 in UC Rats.