Publication:
Chelerythrine-mediated targeting of NF-κB and Nrf2 pathways alleviates liver injury in a carbon tetrachloride-induced liver fibrosis mouse model

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Ding-40-1805-1815-2025.pdf(6.88 MB)
Date
2025
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Authors
Ding Yisong ; Li Xiaoming ; Qi Ruixing ; Su Yingshi ; Wang Xiaoli
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Publisher
Universidad de Murcia, Departamento de Histología e Histopatología
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Biología Celular e Histología
DOI
https://doi.org/10.14670/HH-18-892
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info:eu-repo/semantics/article
Description
Abstract
Background and Aims. This study aimed to investigate the mechanism and efficacy of chelerythrine (CHE) in treating carbon tetrachloride (CCl4)-induced liver fibrosis, with a particular focus on the nuclear factor-erythroid-related factor-2 (Nrf2) and nuclear factor-kappa-B (NF-κB) signaling pathways. Methods. Mice were induced with CCl4 for eight weeks and categorized into the control group, CCl4 model group, and CHE low (7 mg/kg/d, ig,), medium (14 mg/kg/d, ig), and high-dose (28 mg/kg/d, ig) groups with 10 animals in each group. Following CHE treatment, liver sample morphology was assessed using multiple immunohistochemistry, and serum biochemical indicators were measured. ELISA was used to determine IL-10, IL-1β, and TNF-α contents. Western blotting and RT-PCR were employed to analyze protein and mRNA levels of α-SMA, Col-I, fibronectin, Nrf2, HO-1, NQO1, GCLc, GCLm, NF-κB, p-NF-κB, IκBα, and p-IκBα. Nrf2 knockout mice were used to assess the impact of CHE on the Nrf2 signaling pathway. Results. The findings demonstrated that CHE significantly ameliorated oxidative damage, inflamma-tory response, and liver fibrosis in CCl4-induced mice. CHE treatment increased Nrf2 expression and its target proteins, including HO-1 and GCLc, an effect not observed in Nrf2 knockout mice. In addition, CHE reduced NF-κB expression levels. Conclusions. These results suggest that CHE can alleviate liver fibrosis in CCl4-induced mice by modulating NF-κB/IκBα and Nrf2 signaling pathways. These findings propose CHE as a potential novel anti-liver fibrosis drug
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Chelerythrine , CCl4 , Liver fibrosis , Nrf2/ NF-κB signaling pathway
Citation
Histology and Histopathology, Volúmen 40,nº11(2025), 1805-1815
URI
http://hdl.handle.net/10201/169689
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Histology and histopathology, Vol.40, Nº11, (2025)
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