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

OBJECTIVES

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 (CCl) in the liver of male Wistar rats.

MATERIALS AND METHODS

Animals were divided into four groups: Control, Pinene, CCl, and CCl.Pinene. Pinene and CCl.Pinene groups were given alpha-pinene (50 mg/kg/day) through intraperitoneal (IP) injections for six consecutive weeks. CCl and CCl.Pinene groups received IP injections of CCl (2 ml/kg twice weekly for six consecutive weeks).

RESULTS

The results revealed that alpha-pinene inhibited enhancing liver enzyme AST (<0.001), ALT (<0.001), ALP (<0.01), and GGT (<0.001) activity in CCl.Pinene rats. It reduced malondialdehyde (<0.05) and nitric oxide (<0.05) levels and increased the catalase enzyme activity (<0.05) and glutathione levels (<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 (<0.01), NF-κB (<0.05), PI3K (<0.05), Akt (<0.05), mTOR (<0.01), TGF-β1 (<0.01), and Smad3 (<0.01) in the liver of rats receiving CCl.

CONCLUSION

We concluded that alpha-pinene reduced CCl-induced liver fibrosis by lowering oxidative stress, suppressing liver inflammation, and inhibiting TLR4/NF-κB, TGF-β/Smad3, and PI3K/Akt/mTOR signaling pathways. Consequently, alpha-pinene may have potential therapeutic value in treating liver diseases.