Alpha-pinene ameliorates liver fibrosis by suppressing oxidative stress, inflammation, and the TGF-β/Smad۳ 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 (CCl۴) in the liver of male Wistar rats. Materials and Methods: Animals were divided into four groups: Control, Pinene, CCl۴, and CCl۴.Pinene. Pinene and CCl۴.Pinene groups were given alpha-pinene (۵۰ mg/kg/day) through intraperitoneal (IP) injections for six consecutive weeks. CCl۴ and CCl۴.Pinene groups received IP injections of CCl۴ (۲ ml/kg twice weekly for six consecutive weeks).Results: The results revealed that alpha-pinene inhibited enhancing liver enzyme AST (P<۰.۰۰۱), ALT (P<۰.۰۰۱), ALP (P<۰.۰۱), and GGT (P<۰.۰۰۱) activity in CCl۴.Pinene rats. It reduced malondialdehyde (P<۰.۰۵) and nitric oxide (P<۰.۰۵) levels and increased the catalase enzyme activity (P<۰.۰۵) and glutathione levels (P<۰.۰۱) 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 TLR۴ (P<۰.۰۱), NF-κB (P<۰.۰۵), PI۳K (P<۰.۰۵), Akt (P<۰.۰۵), mTOR (P<۰.۰۱), TGF-β۱ (P<۰.۰۱), and Smad۳ (P<۰.۰۱) in the liver of rats receiving CCl۴. Conclusion: We concluded that alpha-pinene reduced CCl۴-induced liver fibrosis by lowering oxidative stress, suppressing liver inflammation, and inhibiting TLR۴/NF-κB, TGF-β/Smad۳, and PI۳K/Akt/mTOR signaling pathways. Consequently, alpha-pinene may have potential therapeutic value in treating liver diseases.

کلیدواژه ها:

Alpha-pinene ، Carbon tetrachloride ، Collagen ، Glutathione ، Inflammation ، Toll-like receptor ۴