Alpha-pinene ameliorates liver fibrosis by suppressing oxidative stress, inflammation, and the TGF-β/Smad3 signaling pathway

Objective(s): A monoterpene alpha-pinene possesses anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Here, we investigated the effect of alpha-pinene on molecular, biochemical, and histological changes induced by carbon tetrachloride (CCl4) in the liver of male Wistar rats. Materials and Methods: Animals were divided into four groups: Control, Pinene, CCl4, and CCl4.Pinene. Pinene and CCl4.Pinene groups were given alpha-pinene (50 mg/kg/day) through intraperitoneal (IP) injections for six consecutive weeks. CCl4 and CCl4.Pinene groups received IP injections of CCl4 (2 ml/kg twice weekly for six consecutive weeks). Results: The results revealed that alpha-pinene inhibited enhancing liver enzyme AST (P<0.001), ALT (P<0.001), ALP (P<0.01), and GGT (P<0.001) activity in CCl4.Pinene rats. It reduced malondialdehyde (P<0.05) and nitric oxide (P<0.05) levels and increased the catalase enzyme activity (P<0.05) and glutathione levels (P<0.01) in the liver. Likewise, alpha-pinene suppressed proinflammatory and profibrotic gene expression and prevented significant histological damage and collagen deposition in the liver of these animals. Also, alpha-pinene reduced the expression of TLR4 (P<0.01), NF-kappa B (P<0.05), PI3K (P<0.05), Akt (P<0.05), mTOR (P<0.01), TGF-beta 1 (P<0.01), and Smad3 (P<0.01) in the liver of rats receiving CCl4. Conclusion: We concluded that alpha-pinene reduced CCl4-induced liver fibrosis by lowering oxidative stress, suppressing liver inflammation, and inhibiting TLR4/NF-kappa B, TGF-beta/Smad3, and PI3K/Akt/mTOR signaling pathways. Consequently, alpha-pinene may have potential therapeutic value in treating liver diseases.