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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Hemistepsin A inhibits T0901317-induced lipogenesis in the liver

  • Kim, Jae Kwang (College of Korean Medicine, Daegu Haany University) ;
  • Cho, Il Je (College of Korean Medicine, Daegu Haany University) ;
  • Kim, Eun Ok (College of Korean Medicine, Daegu Haany University) ;
  • Lee, Dae Geon (College of Korean Medicine, Daegu Haany University) ;
  • Jung, Dae Hwa (College of Korean Medicine, Daegu Haany University) ;
  • Ki, Sung Hwan (College of Pharmacy, Chosun University) ;
  • Ku, Sae Kwang (College of Korean Medicine, Daegu Haany University) ;
  • Kim, Sang Chan (College of Korean Medicine, Daegu Haany University)
  • Received : 2020.05.26
  • Accepted : 2020.07.21
  • Published : 2021.02.28
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Abstract

Hemistepsin A (HsA) is a guaianolide sesquiterpene lactone that inhibits hepatitis and liver fibrosis. We evaluated the effects of HsA on liver X receptor (LXR)-mediated hepatic lipogenesis in vitro and in vivo. Up to 10 μM, HsA did not affect the viability of HepG2 and Huh7 cells. Pretreatment with 5-10 μM HsA significantly decreased the luciferase activity of the LXR response element, which was transactivated by T0901317, GW 3965, and LXRα/retinoid X receptor α overexpression. In addition, it significantly inhibited the mRNA expression of LXRα in HepG2 and Huh7 cells. It also suppressed the expression of sterol regulatory element-binding protein-1c and lipogenic genes and reduced the triglyceride accumulation triggered by T0901317. Intraperitoneal injection of HsA (5 and 10 mg/kg) in mice significantly alleviated the T0901317-mediated increases in hepatocyte diameter and the percentage of regions in hepatic parenchyma occupied by lipid droplets. Furthermore, HsA significantly attenuated hepatic triglyceride accumulation by restoring the impaired expression of LXRα-dependent lipogenic genes caused by T0901317. Therefore, based on its inhibition of the LXRα-dependent signaling pathway, HsA has prophylactic potential for steatosis.

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References

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