7-3--dihydroxy-4--methoxyisoflavone and Non-alcoholic-Fatty-Liver-Disease

Chinese herbal monomer hairy Calycosin is a flavonoid extracted from Radix astragali.. The aim of the research was to investigate the effect and mechanism of Hairy Calycosin on Non-Alcoholic Fatty Liver Dieases (NAFLD) in rats.. 60 rats were randomly divided into 6 groups, then NAFLD rat models were prepared and treated with different doses of Hairy Calycosin (0.5, 1.0, 2.0 mg/kg) or Kathyle relatively.. Both 1.0 mg/kg and 2.0 mg/kg Hairy Calycosin treatment could significantly increase the serum Superoxide Dismutase (SOD) content of the model rats and reduce the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Free Fatty Acid (FFA), IL-6, tumor necrosis factor-alpha (TNF-α) and liver homogenate malondialdehyde (MDA), while 2.0 mg/kg Hairy Calycosin can down-regulate liver tissue cytochrome p450 2E1 (CYP2E1). In the electron microscope, compared with the model control group, the mitochondrial swelling in the hepatocytes of Hairy Calycosin (1.0, 2.0 mg/kg) treatment group was significantly reduced, the ridge on the inner membrane of mitochondria increased, and the lipid droplets became much smaller.. Hairy Calycosin can effectively control the lipid peroxidation in liver tissues of rats with NAFLD, and reduce the levels of serum TNF-α, IL-6, MDA and FFA, effectively improve the steatosis and inflammation of liver tissue, and down-regulate the expression of CYP2E1, inhibit apoptosis of hepatocytes.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Astragalus propinquus; Cytochrome P-450 CYP2E1; Disease Models, Animal; Drugs, Chinese Herbal; Fatty Acids, Nonesterified; Hepatocytes; Interleukin-6; Isoflavones; Male; Malondialdehyde; Non-alcoholic Fatty Liver Disease; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Nonalcoholic fatty liver disease (NAFLD) has become a major health concern worldwide. The present study was designed to investigate the effects of calycosin against high-fat diet (HFD)-induced NAFLD in mice.. C57BL/6 J male mice were fed with HFD to induce NAFLD model and treated with or without calycosin for 12 weeks. The levels of ALT, AST, insulin, and adiponectin were measured using biochemical methods. Hemotoxylin and eosin staining and Oil Red O staining were used to determine the liver histopathology changes and measure the degree of lipid accumulation respectively. Glucose tolerance tests and insulin tolerance tests were performed followed by quantitative insulin sensitivity check index determination. Western blot and quantitative real-time polymerase chain reaction were used to explore the potential mechanism involved in the beneficial effects of calycosin.. Calycosin effectively decreased the levels of ALT and AST, increased the levels of adiponectin and insulin. Hemotoxylin and eosin staining indicated calycosin treatment remarkably improved liver injury. Oil Red O staining indicated calycosin treatment remarkably improved lipid accumulation. Quantitative insulin sensitivity check index in HFD fed mice was significantly lower than in the standard chow fed mice. Further, calycosin suppressed phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, sterol-regulatory element binding protein 1c, and FASN involved in gluconeogenesis and triglyceride synthesis. Calycosin increased glycogen synthase kinase 3 beta, glucose transporter 4, and phosphorylated insulin receptor substrates 1 and 2 expressions involved in glucose metabolism. The aforementioned beneficial effects of calycosin against HFD-induced NAFLD may be attributed to farnesoid X receptor activation.. Calycosin could produce the favorable effects against HFD-induced NAFLD in mice.

Topics: Adiponectin; Alanine Transaminase; Animals; Aspartate Aminotransferases; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Glucose; Humans; Insulin; Isoflavones; Liver; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease

Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury.. The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH.. The C57BL/6 male mice were fed with methionine choline deficient (MCD) diet for 4 weeks to induce NASH and treated with or without calycosin by oral gavage for 4 weeks.. The body weight, liver weight and the liver to body weight ratios were measured. Serum ALT, AST, TG, TC, FFA, MCP-1 and mKC levels were accessed by biochemical methods. H&E staining and Oil red O staining were used to identify the amelioration of liver histopathology. Immunohistochemistry of a-SMA, Masson trichrome staining and Sirius red staining were used to identify the amelioration of hepatic fibrosis. The quantitative real-time-PCR and Western blot were applied to observe the expression changes of key factors involved in triglyceride synthesis, free fatty acid β-oxidation and hepatic fibrosis.. Calycosin significantly inhibited body weight loss induced by MCD diet, decreased the ALT and AST activities, MCP-1 and mKC in a dose-dependent manner. The H&E and Oil red O staining indicated calycosin effectively improved hepatic steatosis, improved the degree of triglyceride accumulation. Masson trichrome and Sirius red staining indicated that calycosin treatment remarkably attenuated the degree of hepatic fibrosis. Immunohistochemistry of a-SMA demonstrated that calycosin attenuated hepatic fibrosis by inhibiting hepatic stellate cell activation. Further, calycosin inhibited the expression of SREBP-1c, FASN, ACC and SCD1 involved in triglyceride synthesis, promoted the expression of PPARa, CPT1, Syndecan-1 and LPL involved in free fatty acid β-oxidation. The above effects of calycosin were attributed to FXR activation.. Calycosin attenuates triglyceride accumulation and hepatic fibrosis to protect against NASH via FXR activation.

Topics: Animals; Astragalus Plant; Chemokine CCL2; Diet; Disease Models, Animal; Drugs, Chinese Herbal; Isoflavones; Liver; Liver Cirrhosis; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phytotherapy; Receptors, Cytoplasmic and Nuclear; Sterol Regulatory Element Binding Protein 1; Triglycerides