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Schisandrin B (SchB) is one of the most abundant and bioactive dibenzocyclooctadiene derivatives found in the fruit of
Schisandra chinensis. Here, we investigated the potential therapeutic effects of SchB on non-alcoholic fatty-liver disease
(NAFLD). In lipidomic study, ingenuity pathway analysis has highlighted palmitate biosynthesis metabolic pathway in the
liver samples of SchB-treated high-fat-diet-(HFD)-fed mice. Further experiments showed that the SchB treatment reduced
expression and activity of fatty acid synthase, expressions of hepatic mature sterol regulatory element binding protein-1, tumor
necrosis factor-�± and hepatic level of palmitic acid which is known to promote progression of steatosis to steatohepatitis.
Furthermore, the treatment also activated nuclear factor-erythroid-2-related factor 2 which is known to attenuate the
progression of NASH-related fibrosis. Interestingly, in fasting mice, a single high-dose SchB induced transient lipolysis and
increased the expressions of adipose triglyceride lipase and phospho-hormone sensitive lipase. The treatment also increased
the plasma cholesterol levels, 3-hydroxy-3-methylglutaryl-CoA reductase activity and reduced the hepatic low-densitylipoprotein
receptor expression in these mice. Our data not only suggested SchB as a potential therapeutic agent for NAFLD,
but also provided important information for a safe consumption of SchB, because SchB overdosed under fasting condition will
have adverse effects on lipid metabolism.