Chinese Journal of Pharmacovigilance ›› 2026, Vol. 23 ›› Issue (10): 1123-1130.
DOI: 10.19803/j.1672-8629.20260012

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Effects of piperlongumine on gut barrier dysfunction in a rat model of carbon tetrachloride-induced liver fibrosis

Zhang Ningfang1, Zhao Li1, Yang Yong2, Yang Hongxin1*   

  1. 1Department of Cell Biology, Inner Mongolia Medical University, Hohhot Inner Mongolia 010110, China;
    2Department of Abdominal Oncology Surgery, Inner Mongolia People’s Hospital, Hohhot Inner Mongolia 010010, China
  • Received:2026-01-02 Online:2026-10-15 Published:2026-10-16

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Abstract: Objective To investigate the mechanism of piperlongumine (PPLGM) against carbon tetrachloride (CCl4)-induced liver fibrosis in rats and its protective effect on the intestinal barrier. Methods Fifty SD rats were randomly divided into the control group, model group, and PPLGM low, medium and high-dose groups (2.5, 5, 10 mg·kg-1). Except the control group, all these groups were subcutaneously injected with 50% CCl4-olive oil solution to construct a liver fibrosis model. After modeling, each administration group was given the corresponding dose of PPLGM by gavage for 4 weeks. After the intervention, blood was taken from the abdominal aorta before liver and intestinal tissues were collected. Hematoxylin and Eosin (HE) and Masson staining were used to assess the pathological changes of liver and intestinal tissues and liver collagen deposition. Such liver function indexes as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using biochemical methods. Immunohistochemistry, Western blot, and RT-qPCR techniques were adopted to detect expression levels of key molecules in the TLR4-NF-κB signaling pathway, fibrosis markers (α-SMA, CollagenⅠ), and intestinal tight junction protein (Claudin-1) in liver and intestinal tissues. The content of endotoxin (LPS) in serum was detected by ELISA. The binding ability of PPLGM to TLR4, NF-κB and TNF-α was analyzed via molecular docking technology. Results Compared with the control group, α-SMA and collagenⅠ expression levels were upregulated in liver tissues and serum ALT and AST levels were elevated in the model group, accompanied by downregulation of claudin-1 protein expressions in colon tissues and increases in serum endotoxin levels (P<0.05). Immunohistochemistry and Western blot analysis suggested significantly increased expression levels of TLR4, NF-κB, and TNF-α in liver and intestinal tissues (P<0.05). Following treatment with PPLGM, the above abnormalities were significantly reversed in that liver fibrosis was markedly improved pathologically, serum ALT and AST levels were decreased significantly, expression levels of α-SMA, collagen Ⅰ, and the TLR4/NF-κB/TNF-α pathway were downregulated, claudin-1 expression was recovered, and serum LPS levels were decreased (P<0.05). Molecular docking results indicated that the binding affinity of PPLGM to TLR4, NF-κB, and TNF-α was less than -5 kcal·mol-1. Conclusion PPLGM can significantly improve CCl4-induced liver fibrosis and intestinal barrier dysfunction by regulating the gut-liver axis. This compound may block the transmission of intestinal-derived inflammatory signals to the liver by inhibiting the TLR4/NF-κB signaling pathway triggered by intestinal barrier damage, thereby reducing the liver inflammatory microenvironment and fibrosis process.

Key words: Piperlongumine, Liver Fibrosis, TLR4, Enterohepatic Axis, Endotoxin（LPS）, Intestinal Barrier, Rat

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