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Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease in which a large amount of fat accumulates in hepatocytes due to lipid metabolism disorders. Conventional anti-inflammatory and transaminase-lowering treatment regimens often have an unsatisfactory therapeutic effect, and restoring the normal biosynthesis and metabolism of lipids is the key to the treatment of NAFLD. Studies have shown that brown adipose tissue can improve metabolic diseases by enhancing insulin sensitivity and regulating lipid metabolism, and the treatment of NAFLD by promoting white fat browning has attracted wide attention in the medical field. This article reviews the mechanism of white fat browning in improving NAFLD and summarizes the hepatokines that can promote white fat browning, so as to provide new ideas for the clinical treatment of NAFLD.
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Objective To investigate the effect of Huatan Qushi Huoxue prescription on lipopolysaccharide (LPS)-induced pyroptosis of RAW264.7 cells and its mechanism. Methods An in vitro cell model of LPS-induced activated RAW264.7 was established and divided into blank group, model group, high-, middle-, and low-dose Huatan Qushi Huoxue prescription groups, and control group. The corresponding drug-containing serum intervention was performed for 24 hours. A scanning electron microscope was used to observe cell morphology, and immunofluorescence assay was used to perform quantitative localization of GSDMD-N. Results The cells in the blank group were round and regular in shape with smooth surface, and those in the control group were swollen, with folds on the surface and gaps in the capsule, which were consistent with the morphology of cell pyroptosis. The cells in the control group had bubbles on the surface with obvious pseudopodia and pores in cell membrane, and those in the high-dose group were not swollen and had a rough surface with pseudopodia, with no obvious pores in cell membrane. The cells in the low- and middle-dose groups were swollen and had a rough surface of cell membrane with pores and pseudopodia. Immunofluorescence assay showed that compared with the blank group, the model group had a significant increase in the positive staining intensity of GSDMD-N, and compared with the model group, the control group and the Traditional Chinese medicine group had a reduction in the positive staining intensity of GSDMD-N. Conclusion Huatan Qushi Huoxue prescription can improve the pyroptosis of macrophages and reduce the expression of GSDMD-N.
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Objective To investigate the effect of Huatan Qushi Huoxue prescription on the ultrastructure of hepatocyte mitochondria in a rat model of nonalcoholic steatohepatitis (NASH). Methods A total of 48 male Sprague-Dawley rats were randomly divided into blank group, model group, Yishanfu group, and Huatan Qushi Huoxue prescription group, with 12 rats in each group. The rats in the model group and the drug groups were administered and modeled since week 2; the rats in the blank group were given normal diet, and those in the other three groups were given high-fat diet. Based on dose conversion between human and animal, the equivalent dose of Huatan Qushi Huoxue prescription was 1.26 g/100 g body weight, and the equivalent dose of polyene phosphatidylcholine capsules (Yishanfu) was 0.014 18 g/100 g body weight. The rats in the model group were given 0.9% sodium chloride by gavage, those in the Yishanfu group were given polyene phosphatidylcholine suspension by gavage, and those in the traditional Chinese medicine group were given the granules of Huatan Qushi Huoxue prescription by gavage, once a day for 10 consecutive weeks. A transmission electron microscope was used to observe liver ultrastructure and perform a quantitative analysis. A one-way analysis of variance was used for comparison of continuous data between multiple groups; for further pairwise comparison, the least significant difference t -test was used for data with homogeneity of variance, and the Dunnett's T3 was used for data with heterogeneity of variance. Results The model group had a large number of lipid droplets accumulated in hepatocytes, changes in mitochondrial morphology and structure, and reductions in the number of mitochondria and endoplasmic reticulum. The Huatan Qushi Huoxue prescription group had a significant reduction in lipid droplets in hepatocytes and significant increases in the number of mitochondria and endoplasmic reticulum compared with the model group, with intact mitochondrial membrane and structure. The Yishanfu group had a reduction in lipid droplets in hepatocytes, an increase in the number of mitochondria, and a reduction in the number of endoplasmic reticulum, with relatively intact mitochondrial membrane and structure. The quantitative analysis showed that compared with the blank group, the model group had a significant increase in the area of lipid droplets and a significant reduction in mitochondria, with a significant difference in mitochondrial density between the two groups (all P < 0.01); after drug intervention, the Yishanfu group had a significant reduction in the area of lipid droplets and a significant increase in the number of mitochondria, with a significant difference in mitochondrial density between the Yishanfu group and the model group (all P < 0.01); compared with the Yishanfu group, the traditional Chinese medicine group had a significantly greater reduction in the area of lipid droplets and a significant increase in the number of mitochondria, with a significant difference in mitochondrial density between the two groups (all P < 0.05). Conclusion Huatan Qushi Huoxue prescription can improve lipid accumulation, increase mitochondrial density, and protect mitochondrial structure and function, with a better clinical effect than Yishanfu.
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OBJECTIVE To establish the fingerprint of Huatan qushi huoxue decoction （HQHD），and to explore the effects of processing and decoction methods on its components. METHODS Using salvianolic acid B as reference ，HPLC fingerprints of 10 batches of single and mixed decoction of crude drugs ，single and mixed decoction of processed products （original formula referred to 8 ingredients were crude drugs ；processed formula referred to processed products of Alisma orientale ，Salvia miltiorrhiza ， Curcumae Radix and Bupleuri Radix ，and crude drugs of other ingredients ；single decoction referred to the mixing of each ingredient after being decocted separately ；mixed decoction refers to decocting after mixing all ingredients ）were stablished by Similarity Evaluation System of Chromatographic Fingerprints of Traditional Chinese Medicine （2012 edition）. The similarity evaluation，common peak identification and attribution ，chemical pattern recognition analysis were also carried out. RESULTS There were 37 common peaks in each fingerprint of 10 batches of single and mixed decoction of crude drugs ，single and mixed decoction of processed ，the similarities with control fingerprint were higher than or close to 0.950. Nine common peaks were identified，i.e. rutin （peak 12），hesperidin（peak 13），salvianolic acid B （peak 16），quercetin（peak 20），silybin（peak 22）， luteolin（peak 23），autrantio-obtusin（peak 29），23-acetylalismol C （peak 34），saikosaponin b 2（peak 35）；decoction pieces of 8 ingredients all contributed to the fingerprints of HQHD. Principal component analysis （PCA）showed that the 4 kinds of HQHD samples were grouped into one category ，respectively. The clustering result of partial least squares-discriminant analysis was consistent with that of PCA. Corresponding components of peak 1，15，17，18 and 36，salvianolic acid B and luteolin m ay be the differential markers of the quality for mixed decoction samples of crude drugs and processed products ； corresponding components of peak 1，7，17-19，salvianolic acid B and hesperidin may be the differential markers of the quality for single decoction samples of crude drugs and processed products；corresponding components of peak 1，17-19，36， salvianolic acid B and luteolin may be the differential markers of the quality for single decoction and mixed decoction samples of crude drugs ；corresponding components of peak 7，17-19，21， hesperidin，salvianolic acid B ，rutin，luteolin and autrantio-obtusin may be the differential markers of the quality for single decoction and mixed decoction samples of processed products. CONCLUSIONS The established fingerprint of HQHD is stable and reliable. The quality differential components of different decoction samples are luteolin ，hesperidin，etc. The quality differential components of samples processed or not are rutin ，hesperidin，autrantio-obtusin，etc.
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Ferroptosis is a type of iron-dependent cell death driven by lipid peroxidation, and its mechanism is associated with iron homeostasis imbalance, lipid peroxidation, and slC7A11-GSH-GPX4 antioxidant system. Ferroptosis plays a key role in the development and progression of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and inhibition of ferroptosis can almost completely inhibit the development of NASH. This article reviews the research advances in the mechanism of ferroptosis and its role in NAFLD/NASH and proposes the research strategies and technical means for ferroptosis, so as to provide a reference for research on the mechanism of NAFLD/NASH.
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MicroRNA(miRNA) affect various biological processes such as cell differentiation, proliferation, and apoptosis by inhibiting the translation of target genes after transcription and are widely involved in the regulation of immune and inflammatory responses in organisms. Autoimmune liver diseases are a group of chronic inflammatory diseases of the hepatobiliary system mediated by abnormal immunity, and abnormal immune inflammatory response of liver tissue with the involvement of miRNA is closely associated with the development and progression of autoimmune liver diseases. This article reviews the current research advances in miRNA in autoimmune liver diseases.
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Metabolic associated fatty liver disease (MAFLD) is currently one of the most important liver diseases worldwide, and its incidence rate is increasing year by year. This article summarizes the current research status of medical treatment of MAFLD, including lifestyle changes and individualized drug treatment. Lifestyle changes include diet management, exercise intervention, biological clock adjustment, and psychological intervention, and individualized drug treatment includes insulin sensitizer, vitamin E, weight-loss and lipid-lowering drugs, liver-protecting and transaminase-lowering drugs, and traditional Chinese medicine treatment. At the same time, multidisciplinary treatment is the trend of clinical treatment of MAFLD.
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Nonalcoholic fatty liver disease (NAFLD) is one of the most important liver diseases worldwide. Traditional Chinese medicine has a significant effect in the treatment of NAFLD, possibly by improving lipid metabolism, reducing liver inflammation, regulating intestinal flora, improving innate immunity, and reducing liver fibrosis. This article summarizes the current data on the mechanism of action of traditional Chinese medicine in the treatment of NALFD, so as to provide a reference for clinical application.
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The incidence rate of nonalcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC) is gradually increasing. Its pathogenesis is associated with the changes in genetic and epigenetic modifications, metabolism, immunity, intestinal microecology, endocrine pathways, and circadian rhythm. This article summarizes the available data on the pathogenesis of NAFLD-HCC and points out that HCC is caused by the interactions between multiple factors.