2. Academic Validation
  3. Involvement of activation of PLIN5-Sirt1 axis in protective effect of glycycoumarin on hepatic lipotoxicity

Involvement of activation of PLIN5-Sirt1 axis in protective effect of glycycoumarin on hepatic lipotoxicity

  • Biochem Biophys Res Commun. 2020 Jul 12;528(1):7-13. doi: 10.1016/j.bbrc.2020.05.072.
Enxiang Zhang 1,  Shutao Yin 1,  Chong Zhao 1,  Lihong Fan 2,  Hongbo Hu 3
Affiliations

Affiliations

  • 1 Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, China.
  • 2 College of Veterinary Medicine, China Agricultural University, China. Electronic address: [email protected].
  • 3 Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, China. Electronic address: [email protected].
PMID: 32448510 DOI: 10.1016/j.bbrc.2020.05.072
Abstract

Licorice is a popular medicinal plant, and it has been used to treat various diseases, including liver diseases. Glycycoumarin (GCM) is a major coumarin compound isolated from licorice with favorable bioavailability property. Our previous studies have shown that GCM is capable of inhibiting lipoapoptosis in both Cell Culture and methionine-choline-defcient (MCD) diet-induced mouse model of non-alcoholic steatohepatitis (NASH) through mechanisms involving suppression of endoplasmic reticulum (ER) stress. Perilipin 5 (PLIN5), a newly identified lipid drop protein in the perilipin family, is highly expressed in oxidative tissues including the liver and is suggested to play an important role in protecting against hepatic lipotoxicity. Give the hepatoprotective role of PLIN5, we hypothesized that induction of PLIN5 might contribute to the hepatoprotective effect of GCM via mitigating ER stress and inflammatory responses. Results showed that PLIN5 and its downstream target SIRT1 were induced by GCM both in vitro and in vivo. Inhibition of either PLIN5 or SIRT1 led to significantly attenuated protective effect of GCM on palmitic acid (PA)-induced lipoapoptosis and inflammatory responses, supporting involvement of PLIN5-Sirt1 axis in the protective effect of GCM on hepatic lipotoxicity. The findings of the present study provide novel insight into the understanding of mechanisms underlying the hepatoprotective effect of GCM.

Keywords

ER stress; Glycycoumarin; Inflammation; Lipotoxicity; PLIN5; Sirt 1.

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