Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, inflammation and gut dysbiosis. Paeoniflorin (PAF) exhibits potential against NAFLD, yet its antioxidant mechanism via the gut-liver axis remains unclear. In a high-fat/sucrose (HFS) diet-induced NAFLD mouse model, C57BL/6 mice received PAF (50 or 100 mg/kg/day) for 10 weeks. Oxidative stress markers, histopathology, gut microbiota, and serum metabolomics were conducted, with fecal microbiota transplantation (FMT) applied for causal validation. PAF ameliorated metabolic disorders by suppressing hepatic lipogenesis and promoting cholesterol excretion. PAF significantly ameliorated oxidative stress by enhancing hepatic and colonic anti-oxidant capacity, evidenced by increased SOD activity and decreased MDA levels. It concurrently reduced systemic inflammation and enhanced intestinal barrier integrity via upregulation of tight junction proteins. Furthermore, PAF reshaped the gut microbiota, elevating beneficial Akkermansia and microbial-derived SCFAs, while suppressing pro-oxidant and pro-inflammatory pathogens like Desulfovibrio and Helicobacter. FMT confirmed that these antioxidant and metabolic benefits were mediated by the gut microbiota. In conclusion, PAF alleviates NAFLD primarily through potent antioxidant actions and anti-inflammatory, achieved via remodeling gut microbial ecology and reinforcing intestinal barrier.

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.