Taraxasterol, a pentacyclic-triterpene compound, is one of the main active components isolated from the traditional Chinese medicinal herb Taraxacum. The objective of this study is to evaluate the protective effects of taraxasterol and its possible underlying mechanisms against ethanol-induced liver injury in mice. ICR mice were fed with Lieber-DeCarli diet containing 5% ethanol for 10 d and then challenged with a single dose of 20% ethanol (5 g/kg BW) by intragastric administration. The mice were intragastrically treated daily with taraxasterol (2.5, 5, and 10 mg/kg). Tiopronin was used as a positive control. The liver index was calculated, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in sera were detected. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) and the activity of superoxide dismutase (SOD) in the livers were measured. The histopathological changes of liver tissues were observed by hematoxylin and eosin (H&E) staining. The protein expression levels of hepatic cytochrome P450 2E1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (Nrf2), antioxidant protein heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) signaling pathway in liver tissues were detected by immunohistochemistry and Western blot methods. Taraxasterol significantly reduced the ethanol-induced increases of liver index, ALT, AST, and TG levels in sera and TG and MDA contents in the livers and hepatic ROS production and suppressed the ethanol-induced decreases of hepatic GSH level and SOD activity. Taraxasterol also significantly inhibited the secretion of proinflammatory cytokines TNF-α and IL-6 induced by ethanol. In addition, taraxasterol improved the liver histopathological changes in mice with ethanol-induced liver injury. Further studies revealed that taraxasterol significantly inhibited the ethanol-induced upregulation of CYP2E1, increased the ethanol-induced downregulation of Nrf2 and HO-1, and inhibited the degradation of inhibitory kappa Bα (IκBα) and the expression level of NF-κB p65 in liver tissues of ethanol-induced mice. These findings suggest that taraxasterol possesses the potential protective effects against ethanol-induced liver injury in mice by exerting antioxidative stress and anti-inflammatory response via CYP2E1/Nrf2/HO-1 and NF-κB signaling pathways.

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Immune hepatic injury is a liver disease closely related to an immune imbalance of T cells and macrophages. Our previous series of studies have demonstrated that taraxasterol isolated from Taraxacum possesses great anti-inflammatory and immunomodulatory effects in vivo and in vitro. In this study, we explored the preventive effects of taraxasterol and its underlying mechanisms on concanavalin A (Con A)-induced acute hepatic injury in mice. It was found that treatment with taraxasterol significantly decreased the Con A-induced increase of liver index, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and hepatic malondialdehyde (MDA) levels, and increased the Con A-induced decrease of hepatic glutathione (GSH) and superoxide dismutase (SOD) production. Taraxasterol also significantly inhibited the release of pro-inflammatory cytokines tumour necrosis factor-a (TNF-a), interleukin-6 (IL-6), IL-1b, interferon-c (IFN-c) and IL-4. In addition, treatment with taraxasterol alleviated the hepatic histopathological injury and apoptosis induced by Con A. Furthermore, taraxasterol dramatically down-regulated the expressions of T toll-like receptor (TLR2), TLR4 and nuclear factor-jappaB (NF-jB) p65, and decreased the expression ratio of Bax/Bc1-2 in hepatic tissues. These findings suggest that taraxasterol prevents Con A-induced acute hepatic injury in mice by inhibiting TLRs/NF-jB inflammatory signalling pathway and promoting Bax/Bc1-2 anti-apoptotic signalling pathway.

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