Spenceria ramalana Trimen total polyphenols modulate the inflammatory response and intestinal flora in DSS-induced ulcerative colitis in C57BL/6 mice

Abstract

Ethnopharmacological relevance: Spenceria ramalana Trimen is a perennial herb of the genus Spenceria in the family Rosaceae, the roots of which can be used as medicine. It is mainly distributed in Tibet autonomous region, Yunnan province, and Sichuan province of P. R. China at an altitude of 2950∼5000 m. Spenceria ramalana Trimen has been documented to have laxative, antidiarrheal, and balancing effects. Plant polyphenols with significant anti-inflammatory and antioxidant effects appear to have therapeutic potential for ulcerative colitis. However, the mechanism of SRT total polyphenols on ulcerative colitis (UC) are still unclear. Aim of the study: To investigate the pharmacological effects and the potential mechanisms of Spenceria ramalana Trimen total polyphenols on dextran sodium sulfate (DSS)-induced UC in C57BL/6 mice. Methods: The components of Spenceria ramalana Trimen total polyphenols were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the therapeutic targets of the bioactive components and UC related targets were collected by searching the database to obtain their intersection targets. The “drug-component-target” network and protein interaction network were constructed for screening the key components and potential targets. DSS-induced UC model in C57BL/6 mice was constructed for the experimental verification of Spenceria ramalana Trimen total polyphenols through systematic evaluation, histopathological analysis, expression levels of inflammatory cytokines, and gut microbiota analysis. Results: A total of 84 Spenceria ramalana Trimen polyphenolic components were detected, including 25 core components. 138 UC related targets were collected and 22 core targets were included. Enrichment analysis showed that the intersection targets were involved in various inflammation-related pathways and functions. Animal experiments revealed that Spenceria ramalana Trimen total polyphenols reduced the DAI score and histological index score, and significantly inhibited the shortening of the colon length. Spenceria ramalana Trimen total polyphenols significantly decreased the contents of TNF-α, IL-6, TGF-β, and the mRNA expression levels of TNF-α, IL-6, IL-1β, TGF-β were also significantly down-regulated in colon tissues. Oxidative stress-related indicators were not significantly regulated by Spenceria ramalana Trimen total polyphenols, and the mRNA expression levels of Nrf2 and HO-1 were inhibited compared with the model group. Gut microbiota analysis showed that Spenceria ramalana Trimen total polyphenols could alleviate the DSS-induced intestinal flora dysbiosis. Conclusion: Spenceria ramalana Trimen total polyphenols could significantly alleviate DSS-induced UC, and the potential mechanism might be related to the regulation of the expression levels of TNF signaling pathway-related factors and the restoration of gut microbiota homeostasis.

Keywords

• Spenceria ramalana Trimen
• Ulcerative colitis
• Polyphenols
• Gut microbiota
• Network pharmacology