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Exploring the Mechanism of Xianggou Polysaccharide in the Treatment of Nonalcoholic Fatty Liver Disease in Mice Based on Proteomics

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by lipid deposition in hepatocytes, and its incidence is increasing annually, with currently limited treatment options available. Xianggou is a well-known medicinal and edible herb in China, traditionally used for its effects in invigorating the spleen, promoting appetite, and dispelling wind-dampness. In this study, polysaccharides were isolated and purified from Xianggou. Furthermore, the therapeutic mechanism of Xianggou polysaccharides in treating NAFLD was investigated using proteomics.

ORGANISM(S): Mus Musculus

SUBMITTER: Shuanghu Wang

PROVIDER: PXD075735 | iProX | Tue Mar 17 00:00:00 GMT 2026

REPOSITORIES: iProX

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Project description:The pathological progression of nonalcoholic fatty liver disease (NAFLD) is driven by multiple factors, and nonalcoholic steatohepatitis (NASH) represents its progressive form. In our previous studies, we found that bicyclol had beneficial effects on NAFLD/NASH. Here we aim to investigate the underlying molecular mechanisms of the bicyclol effect on NAFLD/NASH induced by high-fat diet (HFD) feeding. A mice model of NAFLD/NASH induced by HFD-feeding for 8 weeks was used. As a pretreatment, bicyclol (200 mg/kg) was given to mice by oral gavage twice daily. Hematoxylin and eosin (H&E) stains were processed to evaluate hepatic steatosis, and hepatic fibrous hyperplasia was assessed by Masson staining. Biochemistry analyses were used to measure serum aminotransferase, serum lipids, and lipids in liver tissues. Proteomics and bioinformatics analyses were performed to identify the signaling pathways and target proteins. The real-time RT-PCR and Western blot analyses were performed to verify the proteomics data. As a result, bicyclol had a markedly protective effect against NAFLD/NASH by suppressing the increase of serum aminotransferase, hepatic lipid accumulation and alleviating histopathological changes in liver tissues. Proteomics analyses showed that bicyclol remarkably restored major pathways related to immunological responses and metabolic processes altered by HFD feeding. Consistent with our previous results, bicyclol significantly inhibited inflammation and oxidative stress pathway related indexes (SAA1, GSTM1 and RDH11). Furthermore, the beneficial effects of bicyclol were closely associated with the signaling pathways of bile acid metabolism (NPC1, SLCOLA4 and UGT1A1), cytochrome P450-mediated metabolism (CYP2C54, CYP2C70 and CYP3A25), biological processes such as metal ion metabolism (Ceruloplasmin and Metallothionein-1), angiogenesis (ALDH1A1) and immunological responses (IFI204 and IFIT3). These findings suggested that bicyclol is a potential preventive agent for NAFLD/NASH by targeting multiple mechanisms in future clinical investigations.

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Exploring the Mechanism of Xianggou Polysaccharide in the Treatment of Nonalcoholic Fatty Liver Disease in Mice Based on Proteomics

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