title: Protective Effects of Alisma orientale Extract against Hepatic Steatosis via Inhibition of Endoplasmic Reticulum Stress.
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.
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. ckone0506@hanmail.net.|Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. ckone0506@hanmail.net.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Jang
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. coolyuran@hotmail.com.|Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. coolyuran@hotmail.com.
authors.forename: Yu-Ran
authors.initials: YR
authors.lastname: Han
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. hidejsugi@naver.com.|Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. hidejsugi@naver.com.
authors.forename: Jeong Soo
authors.initials: JS
authors.lastname: Nam
authors.affiliation: Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. yeast10@hanmail.net.
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Han
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. vision@pusan.ac.kr.|Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. vision@pusan.ac.kr.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. jhsol33@pusan.ac.kr.
authors.forename: Han-Sol
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. jung0603@pusan.ac.kr.|Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si 626-870, Korea. jung0603@pusan.ac.kr.
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Jung
mesh_terms: D034902:Alisma / Q000737:chemistry*; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014415:Tunicamycin / Q000009:adverse effects
chemical_list: D001055:Apolipoproteins B; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D010936:Plant Extracts; D020011:Protective Agents; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor; D014415:Tunicamycin
keywords: Alisma orientale; ApoB secretion; endoplasmic reticulum stress; hepatic steatosis; lipogenesis; triglyceride accumulation; very low-density lipoprotein receptor