The development, progression, recurrence, and metastasis of hepatocellular carcinoma (HCC) are closely associated with an abnormal liver-regenerating microenvironment (LRM). Therefore, preventing and reversing an abnormal LRM is a potential therapeutic strategy against HCC. Studies are increasingly focusing on the impact of regeneration, fibrosis, angiogenesis, inflammation, immunomodulation, and hepatic stem cells on HCC development and progression. As a key epigenetic mechanism, DNA methylation is extensively involved in regulating physiological and pathological pathways. In this review, we summarize recent findings on the role of DNA methylation in the fibrotic, angiogenic, inflammatory/immune, and stem cell microenvironments of HCC, and discuss new advances in Traditional Chinese Medicine (TCM) on influencing the abnormal LRM, so as to gain new insights into alleviating the abnormal LRM via regulating DNA methylation by TCM.

Aim. Fuyang Jiedu Huayu (FYJDHY) granules are a combination of five traditional Chinese medicines with known therapeutic effects against chronic liver failure (CLF). The aim of the present study was to investigate the efficacy of FYJDHY to ameliorate the effects of carbon tetrachloride- (CCl4-) induced CLF in rats and to explore the possible molecular mechanisms underlying its therapeutic efficacy. Methods. A model of chronic liver failure was established by intraperitoneal injection of 50% carbon tetrachloride into SD rats for 8 weeks. After establishing the model, rats were treated with either low-dose (4.725 kg/d), medium-dose (9.45 kg/d), or high-dose (18.9 g/kg/d) FYJDHY for 2 weeks. After treatment, samples of liver tissue and blood were harvested from rats in each group. Serum ALT, AST, and TBIL levels and prothrombin time were measured using a biochemical analyzer. The expression of Gab1 (Grb2-associated binder 1), TPO (thrombopoietin), and its receptor c-Mpl were measured using quantitative real-time PCR (RT-PCR) and Western blot analysis, and assessment of histological improvement in liver tissue was by H&E-stained tissue sections. Results. Compared with the model group, serum ALT, AST, and TBIL levels and PT of rats in the intervention group were significantly reduced ( P < 0.05 ). In addition, FYJDHY alleviated pathological damage to liver tissue and increased the expression of Gab1, TPO, and its receptor c-Mpl in liver tissue, to levels statistically significant compared with the model group ( P < 0.05 ). Conclusions. The therapeutic effect of FYJDHY on CLF may be related to the promotion of angiogenesis and improvement in hemopoietic function in individuals suffering from CLF.