Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways.

Studies have reported that taraxasterol (TAR) is effective in the treatment of immune liver injury and alcoholic liver injury. The mechanism of action is mainly related to the inhibition of inflammation. To determine the key molecular mechanisms for the effect of TAR on alleviating ethanol and high-fat diet-induced liver injury, pathological morphology, biochemistry, oxidative stress, inflammatory response and lipid metabolism were examined. Our results showed that TAR could inhibit ethanol-induced hepatocyte death or lipid accumulation, and suppress oxidative stress, inflammatory response and lipid metabolism disorders. More specifically, ethanol-induced TLR-4 and MyD88 inflammatory response were down-regulated, when treated with TAR. Production of CYP2E1, Nrf2 and HO-1, which produced in response to increased oxidative stress, were regulated in TAR treated, ethanol-induced hepatocytes. In summary, TAR could inhibit the inflammatory response and oxidative stress, which was related to the regulation of TAR on TLR-4/MyD88/NF-κB and Nrf2/HO-1 pathways.

Scoparone alleviates hepatic fibrosis by inhibiting the TLR-4/NF-κB pathway.

The aim of this study was to investigate the role of scoparone (SCO) in hepatic fibrosis. For this, we conducted in vivo and in vitro experiments. In vivo rats that were divided into six groups, control, carbon tetrachloride, and colchicine, as well as SCO groups, SCO50, SCO100, and SCO200 treated with 50, 100, and 200 mg/kg SCO doses, respectively. Furthermore, SCO was shown to inhibit Toll-like receptor-4 (TLR-4)/nuclear factor kappa-B (NF-κB; TLR-4/NF-κB) signals by inhibiting TLR-4, which in turn downregulates the expression of MyD88, promotes NF-κB inhibitor-α, NF-κB inhibitor-ß, and NF-κB inhibitor-ε activation, while inhibiting NF-κB inhibitor-ζ. Subsequently, the decrease of phosphorylation of nuclear factor-κB levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 beta, thus weakening hepatic fibrosis. Notably, the SCO200 treated group presented the most significant improvement. Hence, we conclude that SCO alleviates hepatic fibrosis by inhibiting TLR-4/NF-κB signals.

Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR-4/NF-κB and AMPK/Nrf2 signalling pathways.

The purpose of this study was to alleviate liver disturbance by applying polysaccharides from Dicliptera chinensis (DCP) to act on the adenosine monophosphate-activated protein kinase/ nuclear factor erythroid 2-related factor 2 (AMPK/ Nrf2) oxidative stress pathway and the Toll-like receptor 4 (TLR-4)/ nuclear factor kappa-B (NF-κB) inflammatory pathway and to establish an in vivo liver disturbance model using male C57BL/6J and TLR-4 knockout (-/- ) mice. For this, we evaluated the expression levels of SREBP-1 and Nrf2 after silencing the expression of AMPK using siRNA technology. Our results show that with regard to the TLR-4/ NF-κB inflammatory pathway, DCP inhibits TLR-4, up-regulates the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduces the expression of phospho(p)-NF-κB and leads to the reduction of downstream inflammatory factors, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß, thereby inhibiting the inflammatory response. Regarding the AMPK/ Nrf2 oxidative stress pathway, DCP up-regulates the expression of p-AMPK and Nrf2, in addition to regulating glucose and lipid metabolism, oxidative stress and ameliorating liver disturbance symptoms. In summary, our study shows that DCP alleviates liver disturbances by inhibiting mechanisms used during liver inflammation and oxidative stress depression, which provides a new strategy for the clinical treatment of liver disturbance.