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Taoling Yuyang Decoction alleviates DSS-induced ulcerative colitis in mice by regulating gut microbiota -metabolite
Dongyang Liu1, Deshuang Lu2, Ziwen Zhang2
1The First Department of Gastroenterology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
Background:
Traditional Chinese medicine (TCM) offers multi-targeted therapy with few side effects for ulcerative colitis (UC). Taoling Yuyang Decoction (TLYY) has shown clinical efficacy, however, its mechanisms of action are unclear. This study employed a multi-omics approach to elucidate TLYY's therapeutic effects in a murine DSS-induced colitis model.
Methods:
Using a DSS-induced mouse model of colitis, animals were divided into five groups (n = 8): blank control (CK), model (DSS), low- and high-dose TLYY (TLYYL, TLYYH), and positive control (5-ASA). Treatment efficacy was assessed by measuring body weight, disease activity index (DAI), and histopathological changes. Oxidative stress markers (MDA, GSH-Px, SOD) in serum and colon tissues were quantified using commercial kits and immunohistochemistry. Cytokine levels (IL-1β, TNF-α, IL-6) and LPS were measured by ELISA. The expression of tight junction proteins (ZO-1, Occludin, Claudin-1) in colon tissue was analyzed via qPCR and immunocytochemistry. Additionally, 16S rDNA sequencing and metabolomics were employed to examine gut microbiota composition, fecal SCFAs, and differential metabolites.
Results:
Taoling Yuyang Decoction treatment dose-dependently alleviated UC symptoms, including weight loss, colon shortening, and tissue damage. It enhanced antioxidant activities (SOD, GSH-Px) and reduced MDA, suppressed pro-inflammatory cytokines and LPS, and up-regulated tight junction proteins (ZO-1, Occludin, Claudin-1). Gut microbiota analysis showed TLYY-H restored microbial diversity, increased beneficial bacteria (e.g., Lactobacillus, Akkermansia), and decreased harmful genera (e.g., Helicobacter). It also elevated SCFA levels and modulated fecal metabolism, up-regulating anti-inflammatory/antioxidant metabolites while down-regulating toxic compounds. Key pathways such as AGE-RAGE signaling and xenobiotic metabolism were restored.
Conclusion:
Taoling Yuyang Decoction ameliorates DSS-induced colitis via integrated mechanisms involving oxidative stress reduction, anti-inflammation, intestinal barrier repair, and restoration of gut flora homeostasis and metabolic pathways. The superior effect of the high dose highlights its clinical potential for UC treatment.
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