Berberine attenuates ECM accumulation and the progression of acute liver failure through inhibition of NLRP3 inflammasome signalling.

Acute liver failure (ALF) is a life-threatening disease, characterized by upregulated extracellular matrix deposition and inflammatory signalling, with no effective treatment options and targets. The present study was designed to investigate the preventive and therapeutic effects of berberine (BBR) and its underlying mechanism in thioacetamide (TAA)-induced ALF. Male SD rats were administered with TAA 300 mg/kg, i.p., thrice to induce ALF and pre- or post-treated with BBR. To decipher the effects of BBR LFT markers, histopathological analysis of key fibrotic and inflammatory proteins was performed. In addition, the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were assessed by ELISA. Our work showed TAA-induced ALF animals were associated with increased ALT, AST, bilirubin (LFT markers) and histopathological alterations with profuse infiltration of inflammatory cells in the liver tissue. Treatment with BBR has significantly inhibited LFT markers and histological alterations triggered by TAA. In addition, TAA animals demonstrated increased collagen accumulation and upregulated expression of TGF-β1, vimentin, and α-SMA compared to control. The excessive accumulation of collagen, TGF-β1, vimentin, and α-SMA were significantly modulated with BBR treatment. Further, the fluorescence intensity of ROS an activator of NLRP3 including the NLRP3 inflammasome, and its downstream signalling ASC, cleaved IL-1β, and other pro-inflammatory cytokines like TNF-α and IL-6 stimulated by TAA were attenuated by BBR treatment. The current work indicated that BBR significantly ameliorated TAA-induced ALF by inhibiting the extracellular matrix accumulation associated with the NLRP3/IL-1β signalling pathway and could be a viable therapeutic option to treat ALF and other fibroinflammatory diseases.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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