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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. [ABSTRACT FROM AUTHOR]

Quercetin, a natural flavonoid, has been used as a nutritional supplement for its anti-inflammatory and antioxidative properties. Quercetin was reported to exhibit a wide range of pharmacological properties, including its effect on anti-hepatic fibrosis. However, the anti-fibrotic mechanisms of quercetin have not been well-characterized to date. This study aimed to investigate the protective effects of quercetin on carbon tetrachloride (CCl 4 )-induced liver fibrosis in rats and to clarify its anti-hepatofibrotic mechanisms. We demonstrated that quercetin exhibited in-vivo hepatoprotective and anti-fibrogenic effects against CCl 4 -induced liver injury by improving the pathological manifestations, thereby reducing the activities of serum total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and decreasing the serum levels of hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C) and procollagen III peptide (PIIIP). Furthermore, treatment with quercetin 5–15 mg/kg inhibited the activation of NF-κB in a dose-dependent manner via inhibition of IкBα degradation and decreased the expression of p38 MAPK by inhibiting its phosphorylation. Additionally, in a dose-dependent manner, quercetin down-regulated Bax, up-regulated Bcl-2, and subsequently inhibited caspase-3 activation. Moreover, quercetin regulated inflammation factors and hepatic stellate cells (HSCs)-activation markers, such as TNF-α, IL-6, IL-1β, Cox-2, TGF-β, α-SMA, Colla1, Colla2, TIMP-1, MMP-1, and desmin. Taken together, quercetin prevented the progression of liver fibrosis in SD rats. The anti-fibrotic mechanisms of quercetin might be associated with its ability to regulate NF-кB/IкBα, p38 MAPK anti-inflammation signaling pathways to inhibit inflammation, and regulate Bcl-2/Bax anti-apoptosis signaling pathway to prevent liver cell apoptosis. [ABSTRACT FROM AUTHOR]