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Hepatic ischemia–reperfusion injury (HIRI) is of common occurrence during liver surgery and transplantation. Pinocembrin (PIN) is a kind of flavonoid monomer extracted from the local traditional Chinese medicine Penthorum chinense Pursh (P. chinense). However, the effect of PIN on HIRI has not determined. We investigated the protective effect and potential mechanism of PIN against HIRI. Model mice were subjected to partial liver ischemia for 60 min, experimental mice were pretreated with PIN orally for 7 days, and H2O2‐induced oxidative damage model in AML12 hepatic cells was established in vitro. Histopathologic analysis and serum biochemical levels revealed that PIN had hepatoprotective activities against HIRI. The variation of GSH, SOD, MDA, and ROS levels indicated that PIN treatments attenuated oxidative stress in tissue. PIN pretreatment obviously ameliorated apoptosis, and restrained the expression of HMGB1 and TLR4 in vivo. In vitro, compared with H2O2 group, the contents of ROS, mitochondrial membrane potential, apoptotic cells, and Bcl‐2 protein were decreased, while the Bax protein expression was increased. Moreover, HMGB‐1 small interfering RNA test and western blotting showed that PIN pretreatment reduced HMGB1 and TLR4 protein levels. In conclusion, PIN pretreatment effectively protected hepatocytes from HIRI and inhibited the HMGB1/TLR4 signaling pathway.

To investigate the regulatory effect and specific mechanism of the actin-interacting protein zyxin (ZYX) in hepatocellular carcinoma (HCC). HCC is one of the most common malignant tumors in the world which occurrence and development areregulated by multiple genes. We found that the expression of ZYX in HCC tissues was significantly higher than that in normal liver tissues. The results of cell proliferation assay, scratch test and transwell assay showed that high expression of ZYX promoted the proliferation, migration and invasion of hepatoma cell lines (PLC/PRF/5, HCCLM3), inhibiting the expression of ZYX reduced the proliferation, migration, and invasion of hepatoma cells(SK HEP-1, Huh-7). Further analysis found that the expression of cell cycle-related proteins, cell migration and invasion-related proteins were changed when the expression of ZYX changed. Xenograft models showed similar results. The AKT/mTOR signaling pathway is a classic pathway ofcancer development. We found that the phosphorylation level of AKT/mTOR protein was up-regulated with increasing ZYX expression and down-regulated with decreasing ZYX expression. While the addition of the AKT inhibitor MK2206 counteracted the proliferation, migration and invasion of HCC cells with increasing ZYX expression, the AKT activator SC79 also restored the proliferation, migration and invasion of HCC cells with decreasing ZYX expression. Therefore, we speculate that the expression of ZYX may promoting the progression of HCC by activating AKT/mTOR signaling pathway, thereby. This is also the first time to find the mechanism of ZYX in HCC, indicating that ZYX is a possible new target for HCC treatment.

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