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Int. J. Mol. Sci. 2015, 16(11), 26151-26165; doi:10.3390/ijms161125944

Protective Effects of Alisma orientale Extract against Hepatic Steatosis via Inhibition of Endoplasmic Reticulum Stress

1
Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea
2
Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Gopinadhan Paliyath
Received: 4 September 2015 / Revised: 9 October 2015 / Accepted: 21 October 2015 / Published: 2 November 2015
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention)
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Abstract

Endoplasmic reticulum (ER) stress is associated with the pathogenesis of hepatic steatosis. Alisma orientale Juzepzuk is a traditional medicinal herb for diuretics, diabetes, hepatitis, and inflammation. In this study, we investigated the protective effects of methanol extract of the tuber of Alisma orientale (MEAO) against ER stress-induced hepatic steatosis in vitro and in vivo. MEAO inhibited the tunicamycin-induced increase in luciferase activity of ER stress-reporter constructs containing ER stress response element and ATF6 response element. MEAO significantly inhibited tunicamycin-induced ER stress marker expression including GRP78, CHOP, and XBP-1 in tunicamycin-treated Human hepatocellular carcinoma (HepG2) cells and the livers of tunicamycin-injected mice. It also inhibited tunicamycin-induced accumulation of cellular triglyceride. Similar observations were made under physiological ER stress conditions such as in palmitate (PA)-treated HepG2 cells and the livers of high-fat diet (HFD)-induced obese mice. MEAO repressed hepatic lipogenic gene expression in PA-treated HepG2 cells and the livers of HFD obese mice. Furthermore, MEAO repressed very low-density lipoprotein receptor (VLDLR) expression and improved ApoB secretion in the livers of tunicamycin-injected mice or HFD obese mice as well as in tunicamycin or PA-treated HepG2 cells. Alismol, a guaiane-type sesquiterpenes in Alisma orientale, inhibited GRP78 expression in tunicamycin-treated HepG2 cells. In conclusion, MEAO attenuates ER stress and prevents hepatic steatosis pathogenesis via inhibition of expression of the hepatic lipogenic genes and VLDLR, and enhancement of ApoB secretion. View Full-Text
Keywords: Alisma orientale; endoplasmic reticulum stress; hepatic steatosis; triglyceride accumulation; lipogenesis; very low-density lipoprotein receptor; ApoB secretion Alisma orientale; endoplasmic reticulum stress; hepatic steatosis; triglyceride accumulation; lipogenesis; very low-density lipoprotein receptor; ApoB secretion
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Jang, M.-K.; Han, Y.-R.; Nam, J.S.; Han, C.W.; Kim, B.J.; Jeong, H.-S.; Ha, K.-T.; Jung, M.H. Protective Effects of Alisma orientale Extract against Hepatic Steatosis via Inhibition of Endoplasmic Reticulum Stress. Int. J. Mol. Sci. 2015, 16, 26151-26165.

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