actein and Fatty-Liver

Insulin and leptin resistance are highly involved in metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Presently, no approved treatment is available. Actein is isolated from the rthizomes of Cimicifuga foetida, a triterpene glycoside, exhibiting important biological properties, such as anti-inflammatory, anti-cancer, and anti-oxidant activity. However, its effects on metabolic syndrome are poorly understood. The aims of the study were mainly to investigate the molecular mechanisms regulating insulin and leptin resistance, and lipogenic action of actein in high fat diet-fed mice. Our data indicated that actein-treated mice displayed lower body weight, epididymal and subcutaneous fat mass, as well as serum lipid levels. Also, improved insulin and leptin resistance were observed in actein-treated groups. Liver inflammation and fibrosis triggered by high fat diet were decreased for actein administration. Moreover, hepatic lipid accumulation was also reduced by actein along with reductions of hepatic de novo lipogenesis-linked signals in actein-treated rodents with high fat diet. High fat diet-induced activation of insulin receptor substrate 1/Forkhead box protein O1 (IRS1/FOXO1), Janus kinase 2 gene/signal transducer and activator of transcription (JAK2/STAT3) and Protein Kinase B/Glycogen synthase kinase 3 beta (AKT/GSK3β) pathways in liver was inhibited by actein, a potential mechanism by which hyperinsulinemia, hyperleptindemia and dyslipidemia were attenuated. Thus, the findings above might be of nutritional and therapeutic importance for the treatment of NAFLD.

Topics: Animals; Cell Line; Diet, High-Fat; Dyslipidemias; Fatty Liver; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Saponins; Triterpenes

Actein is isolated from the rthizomes of Cimicifuga foetida, which is a triterpene glycoside, displaying suppressive effects on breast cancer cells proliferation. However, the effects of actein treatment on liver injury, tending to cancer, have little to be known. Thus, the study is conducted to explore the role of actein in early liver cancer. Diethylnitrosamine (DEN) was used to induce liver cancer in mice followed by actein treatment at different concentrations. DEN caused steatohepatitis supported by fibrosis and inflammation, which were ameliorated for actein administration. Liver histology of mice with DEN treatment displayed hepatobiliary cysts, reversed by actein. Cell proliferation markers of Cyclin Ds and p53, as well as cancer stem cell markers of CD133 were highly increased in liver tissue samples from DEN-induced mice, and actein showed inhibitory role in these signals expression. Actein-reduced up-regulation of Hif-1α and VEGFR1 in DEN-stimulated liver tissue of mice was seen. Taken together, DEN promoted liver cancer progression, which was ameliorated by actein, supplying a potential therapeutic strategy for liver cancer in future.

Topics: AC133 Antigen; Animals; Antineoplastic Agents, Phytogenic; Carcinogens; Cell Proliferation; Cyclin D; Cytokines; Diethylnitrosamine; Epithelial-Mesenchymal Transition; Fatty Liver; Liver; Liver Neoplasms; Male; Mice; Mice, Inbred C57BL; Neoplastic Stem Cells; Saponins; Signal Transduction; Triterpenes; Tumor Suppressor Protein p53