Salvianolic acid A suppresses CCl₄-induced liver fibrosis through regulating the Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways

Abstract

Salvianolic acid A (SA-A), a water-soluble compound extracted from traditional Chinese herb Radix Salvia miltiorrhiza, has anti-fibrotic effects on carbon tetrachloride (CCl₄)-induced liver fibrosis. However, the underlying molecular mechanism remains unclear. Thus, this study aimed to elucidate the molecular mechanism underlying the anti-fibrotic effects of SA-A on CCl₄-induced liver fibrosis in mice. All mice (except control group) were intraperitoneally administered CCl₄ dissolved in peanut oil to induce liver fibrosis. Treatment groups were then gavaged with SA-A (20 or 40 mg/kg). The liver function index; liver fibrosis index; and superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were determined. Furthermore, histopathological changes in liver tissues were observed via hematoxylin–eosin and Masson's trichrome staining. The expression of α-smooth muscle actin (α-SMA) and collagen I was detected using immunofluorescence, and the mRNA levels of inflammatory factors were determined using quantitative polymerase chain reaction. Finally, western blotting and immunofluorescence were used to determine the expression levels of proteins related to Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways. The results showed that SA-A could ameliorate CCl₄-induced liver injury and liver fibrosis, improve morphology, and alleviate collagen deposition in the fibrotic liver. Moreover, SA-A could regulate the Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways; increase the levels of SOD and GSH-Px; and decrease MDA level in the fibrotic liver. Collectively, our study findings indicate that SA-A is effective in preventing liver fibrosis in mice by inhibiting inflammation and oxidative stress via regulating the Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways.

Keywords:

• Liver fibrosis
• salvianolic acid A
• Nrf2/HO-1
• JAK1/STAT3
• NF-κB/IκBα
• p38 MAPK

Disclosure statement

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant numbers 81803815 and 81973275].