Inhibition of SREBP-1c-mediated hepatic steatosis and oxidative stress by sauchinone, an AMPK-activating lignan in Saururus chinensis

초록

Sauchinone, as an AMP-activated kinase (AMPK)-activating lignan in Saururus chinensis. has been shown to prevent iron-induced oxidative stress and liver Injury Sterol regulatory element binding protein-1c (SREBP-1c) plays a key role in hepatic steatosis, which promotes oxidative stress in obese subjects Previously, we identified the role of AMPK in liver X receptor-alpha (LXR alpha)-mediated SREBP-1c-dependent lipogenesis Because sauchinone as an antioxidant has the ability to activate AMPK, this study investigated its effects on SREBP-1c-dependent lipogenesis in hepatocytes and in high-fat diet (HFD)-induced hepatic steatosis and oxidative injury. Sauchinone prevented the ability of an LXR alpha agonist (T0901317) to activate SREBP-1c. repressing transcription of the fatty acid synthase, acetyl-CoA carboxylase, stearoyl-CoA desaturase-1, ATP-binding cassette transporter A1, and LXRa genes. Consistent with this, an HFD in mice caused fat accumulation in the liver with SREBP-1c induction, which was attenuated by sauchinone treatment Also, sauchinone had the ability to inhibit oxidative stress its shown by decreases in thiobarbituric acid-reactive substance formation, nitrotyrosinylation, and 4-hydroxynonenal production. Moreover. it prevented not only the liver Injury, but also the AMPK inhibition elicited by HFD