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

2009; Elsevier BV; Volume: 48; Issue: 4 Linguagem: Inglês

10.1016/j.freeradbiomed.2009.12.006

1873-4596

Young Woo Kim, Young Mi Kim, Yoon Mee Yang, Tae Hyun Kim, Se Jin Hwang, Jong Rok Lee, Sang Chan Kim, Sang Geon Kim,

Genomics, phytochemicals, and oxidative stress

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-α (LXRα)-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 LXRα 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 LXRα 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 as 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 feeding. These results demonstrate that sauchinone has the capability to inhibit LXRα-mediated SREBP-1c induction and SREBP-1c-dependent hepatic steatosis, thereby protecting hepatocytes from oxidative stress induced by fat accumulation.