Background: Disturbance of the gut microbiota may play a critical role in the progression of nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD). Changes in gut microbiota were analyzed in a rat HFD-induced NAFLD model following treatment with Qinghua Fang (QHF), a Chinese herbal formula currently used in the clinical practice of traditional Chinese medicine. Methods: Sixty Wistar rats were randomly divided into 6 groups (n=10): blank group [normal chow (NC) group], model group (HFD group), control group (BG group), Qinghua Fang high-dose group [QHF(H) group], QHF mid-dose group [QHF(M) group], QHF low-dose group [QHF(L) group]. The high, medium and low doses of QHF were used to intervene in the H, M, and L groups; the BG group was given berberine; the NC and HFD groups were given distilled water for 10 weeks. H&E staining, determination of serum liver function and blood lipid levels, and changes in the structure of rat intestinal flora through 16S rDNA denaturing gradient gel electrophoresis sequencing technology and ERIC-PCR fingerprinting were performed.Results: The liver function and blood lipid levels of the rats in the HFD group were higher than those in the NC group; the alanine aminotransferase levels in the QHF-H group, QFH-M group and QHF-L group were lower than in the HFD group (P<0.05); the liver pathology of the QHF-M group and QHF-H group showed a small amount of fatty cell infiltration, but was significantly less than the hepatocyte inflammation and necrosis in the HFD group. The ERIC-PCR fingerprint and diversity analysis found that the composition of the intestinal flora of rats in the QHF-H group was significantly different from that of the NC and HFD groups. The flora of the QHF and NC groups was more diverse and richer than in the HFD group (P<0.05).Conclusions: QHF alleviated the liver dysfunction and increased blood lipid levels of NAFLD rats induced by HFD. It also effectively reduced the degree of liver steatosis and adjusted the number and structure of intestinal flora. Treatment with QHF had a significant effect on NAFLD.

Objective. Chronic hepatitis B liver fibrosis is an important intermediate link in the development of liver cirrhosis. A retrospective cohort study was conducted in Longhua Hospital affiliated to the Shanghai University of Traditional Chinese Medicine in order to prove whether integrated traditional Chinese and Western medicine could improve the incidence of CHB complications and clinical prognosis. There are 130 patients with hepatitis B liver fibrosis (being treated from 2011–2021) included in the study, and the patients were divided into 64 TCM users (NAs combined with TCM) and 66 TCM nonusers (NAs antiviral therapy). The serum noninvasive diagnostic model (APRI, FIB-4) and LSM value were used to classify the stages of fibrosis. The results showed that the LSM value was decreased significantly in TCM users compared with TCM nonusers (40.63% versus 28.79%). Indicators of FIB-4 and APRI of TCM users have improved significantly compared with that of TCM nonusers (32.81% versus 10.61% and 35.94% versus 24.24%). The AST, TBIL, and HBsAg levels in TCM users were lower than those in TCM nonusers, and the HBsAg level was inversely correlated with the CD3+, CD4+, and CD8+ in TCM users. The PLT and spleen thickness of TCM users also were improved considerably. The incidence rate of end-point events (decompensated cirrhosis/liver cancer) in TCM nonusers was higher than that of TCM users (16.67% versus 1.56%). The long course of the disease and a family history of hepatitis B were the risk factors for disease progression, and long-term oral administration of TCM was the protective factor. As a result, the serum noninvasive fibrosis index and imaging parameters in TCM users were lower than those of TCM nonusers. Patients in the treatment of NAs combined with TCM had better prognoses such as a lower HBsAg level, a more stable lymphocyte function, and a lower incidence of end-point events. The present findings suggest the effect of TCM combined with NAs in the treatment of chronic hepatitis B liver fibrosis is better than that of single drug treatment.

Background: Berberine (BBR) can alleviate nonalcoholic fatty liver (NAFL), but the mechanisms remain uncertain. Mounting evidence has underscored the roles of epigenetic modulation in the development of NAFL. Increased expression of histone methyltransferase SET domain-containing protein 2 (SETD2) is found in the livers of diabetic animals with BBR administration. Whether SETD2 contributes to the protective effects of BBR against NAFL remains to be elucidated. Methods: A C57BL/6 mouse model of NAFL induced by a high-fat high-sucrose diet (HFHS) and a palmitate-treated hepatocyte steatosis model were generated. The effects of BBR were evaluated by Oil Red O staining and the cell viability assay. Quantitative real-time polymerase chain reaction, Western blotting, and immunofluorescence staining were used to analyze the expression and activity of SETD2 and its downstream target trimethylation of lysine 36 on histone 3 (H3K36me3). Results: BBR treatment induced the reduction of lipid droplets in both HFHS mouse livers and HepG2 cells, coincident with the elevation of the mRNA and protein expression of SETD2 and H3K36me3. Knockdown of SETD2 compromised the BBR-mediated inhibition of the accumulation of lipid droplets in the HepG2 cell model of steatosis. Moreover, upregulated SETD2 and H3K36me3 expression was also observed in intact HepG2 cells treated with BBR. The promoter assay indicated that BBR treatment increased the transcriptional activity of SETD2 and H3K36me3. Conclusions: BBR confers hepatoprotection against steatosis through transcriptional regulation of SETD2 activity.

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