Apigenin ameliorates CCl₄-induced hepatic fibrosis by inhibiting hepatic stellate cell activation via PI3K/AKT/GSK3β pathway in mice

Abstract

Objective: To investigate the effect of apigenin on carbon tetrachloride (CCl₄)-induced liver fibrosis and elucidate the underlying mechanisms.

Methods: A mouse model of CCl₄-induced liver fibrosis was used to evaluate the effects of apigenin. Liver function was assessed using biochemical tests, and inflammation-associated markers, including interleukin-1 beta (IL-1β), IL-6, IL-10, and tumor necrosis factor- alpha (TNF-α), were determined by enzyme-linked immunosorbent assay (ELISA). H&E staining, Sirius Red staining, and collagen immunohistochemistry were also conducted. In addition, antioxidant enzyme activity and the underlying mechanisms of hepatoprotective effects of apigenin were examined.

Results: CCl₄ administration induced hepatic stellate cell activation and liver fibrogenesis in mice. Apigenin treatment markedly decreased liver injury markers, inflammation, oxidative stress, and collagen deposition, mitigating CCl₄-induced liver fibrosis. Furthermore, it significantly suppressed the activation of the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K/AKT/GSK3β) pathway by reducing the ratios of p-PI3K/PI3K, p-AKT/AKT, and p-GSK3β/GSK3β in liver tissue.

Conclusions: Apigenin ameliorates CCl₄-induced liver fibrosis in mice, likely through the inhibition of the PI3K/AKT/GSK3β signaling pathway. These findings suggest that apigenin may have therapeutic potential for treating liver fibrosis.

Keywords

Liver fibrosis / CCl₄ / Hepatic stellate cell / PI3K/ AKT/GSK3β / Apigenin

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

This work was supported by the grant from Henan Province Science and Technology Research Project (Project No: 242102310250, 222102310373); Key Research Project Program of Higher Education Institutions in Henan Province (NO 24A32006, 22B360003); Medical Science and Technology Tackling Program of Henan Province (NO LHGJ20230677).

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

TS designed the study and supervised the project. BW collected the data and drafted the manuscript. XL and XZ conducted data analysis and interpretation. YZ performed the analytical calculations. SY and NL contributed to the final approval of the version to be published.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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