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  • br Experimental br Acknowledgements This research was financ

    2020-08-03


    Experimental
    Acknowledgements This research was financially supported by the Scientific and Technological Developing Scheme of Jilin Province of People\'s Republic of China (20150101225JC).
    Introduction Obesity is a serious health risk signal characterized by excess accumulation of triglycerides (TG) in tissue and can be lead to a variety of disorders, such as insulin resistance and hepatic steatosis (Lewis et al., 2002). Diacylglycerol acyltransferase (DGAT) catalyzes the acyl-CoA-dependent acylation of sn-1,2-diacylglycerol and forms triacylglycerol (TAG), which is the terminal and rate-limiting step in TG synthesis and essential Riociguat australia for the formation of adipose tissue (Cui et al., 2012). DGAT enzymes are encoded by two non-homology genes: DGAT1 and DGAT2 (Turchetto-Zolet et al., 2011). In contrast, DGAT1 as a member of the acyl CoA: cholesterol acyltransferase (ACAT) gene family is more homologous with ACAT1 and ACAT2 than with DGAT2, which is more closely related to the monoacylglycerol acyl transferase (MGAT) enzymes (Cases et al., 2001). Recent studies showed: mice that knockout DGAT1 has provided an understanding of relationship between TG synthesis and metabolic syndrome like obesity and type II diabetes. These DGAT1 deficient mice were resistant to weight gain when fed a high-fat diet through mechanisms that involved improve Riociguat australia expenditure and increased sensitivity in insulin and leptin (Chen et al., 2002). Until now, some DGAT1 inhibitors such as JTT-553, PF-04620110, AZD7687 and LCQ908 (DeVita and Pinto, 2013) have been launching clinical trials, but also had a great of limitations. Thus the search for, searching for novel, selective, and orally bio-available DGAT1 inhibitors for the treatment of obesity and type II diabetes has been intensified. Eleutherococcus senticosus (Rupt. & Maxim.) Maxim is a shrub belonging to the Araliaceae, which is commonly distributed in China, Korea, Japan and Russia. It has been traditionally used as folk medicine for the treatment of rheumatism, diabetes, and hepatitis (Nan et al., 2004). Recent phytochemical and biological investigations of Eleutherococcus senticosus found its roots and stem bark include diterpenoids, triterpenoids, lignans, polyacetylenes, phenylpropanoids, diphenyl ethers and flavonoids (Ryu et al., 2004, Li et al., 2015). During the screening of DGAT inhibitors from natural sources, we found a MeOH extract of the stems of A. senticosus exhibited DGAT1 inhibitory activity (>70% inhibition at 30μg/ml) which led us to investigate this plant. Herein, we reported the isolation and structure elucidation of two new compounds along with five known compounds, and the evaluation of their DGAT1 and DGAT2 inhibitory activity (Fig. 1).
    Experimental
    Acknowledgments
    Obesity is a serious health risk that is characterized by an excess accumulation of triglycerides (TG) and can lead to a number of additional conditions including type 2 diabetes, atherosclerosis, hypertension, and cardiovascular disease. Dietary TGs are broken down in the gut to monoacylglycerol and then absorbed in the small intestines. TGs are then reassembled with the sequential addition of two acyl chains. The final step of TG synthesis is catalyzed by the enzyme acyl CoA: diacylglycerol acyltransferase (DGAT) of which there are two forms. Although both DGAT-1 and DGAT-2 are transmembrane proteins found in white adipose tissue, small intestine, liver, and mammary gland, they are from different gene families with distinctive functions. DGAT-1 knockout mice are viable, exhibit resistance to weight gain when fed a high-fat diet, have increased insulin sensitivity, and have increased leptin sensitivity. In contrast, DGAT-2 has an essential role since these knockout mice are not viable due to lipopenia and skin homeostasis abnormalities. DGAT-1 is a member of the acyl CoA: cholesterol acyltransferase (ACAT) gene family and is more homologous with ACAT-1 and ACAT-2 than with DGAT-2 which is more closely related to the monoacylglycerol acyl transferase (MGAT) enzymes. With the resistance to weight gain and positive physiological effects seen in DGAT-1 null mice, an inhibitor of DGAT-1 may be a useful therapy for obesity.