title: Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress.
abstract: BACKGROUND
  Schisandra chinensis (Turcz.) Baill. (SC) is a traditional Chinese herbal medicine with diverse pharmacological activities for treatment of various human diseases. Endoplasmic reticulum (ER) stress is associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of methanol extract of Schisandra chinensis (SC extract) against ER stress-induced NAFLD in vitro and in vivo.
  
  
  METHODS
  The protective effects of SC extract were examined in tunicamycin- or palmitate-treated HepG2 cells in vitro, and in tunicamycin-injected mice or high fed diet (HFD) obese mice in vivo. Expression of ER stress markers including glucose regulated protein 78 (GRP78), C/EBP homolog protein (CHOP), and X-box-binding protein-1 (XBP-1), and triglyceride accumulation were measured in HepG2 cells and in the liver of mice.
  
  
  RESULTS
  SC extract significantly inhibited expression of tunicamycin-induced ER stress markers in tunicamycin-treated HepG2 cells and in the liver of tunicamycin-injected mice, and it also inhibited tunicamycin-induced triglyceride accumulation. Similar observations were made under physiological ER stress conditions such as in palmitate-treated HepG2 cells and in the liver of HFD obese mice. In addition, SC extract repressed the expression of inflammatory genes and lipogenic genes in palmitate-treated HepG2 cells. Schisandrin, an abundant bioactive lignan in SC extract, inhibited the expression of ER stress markers in tunicamycin-or palmitate-treated HepG2 cells, whereas Gomisin J did not affect ER stress markers.
  
  
  CONCLUSIONS
  SC attenuates ER stress and prevents development of NAFLD. SC may be useful as a pharmacological agent for protection against ER stress-induced human diseases.
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea; Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: 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 626-870, Republic of Korea; Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: hidejsugi@naver.com.
authors.forename: Jeong Soo
authors.initials: JS
authors.lastname: Nam
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea; Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: kjh30433@hanmail.net.
authors.forename: Ji Ha
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea; Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: yunyerang@pusan.ac.kr.
authors.forename: Ye-Rang
authors.initials: YR
authors.lastname: Yun
authors.affiliation: Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: 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 626-870, Republic of Korea; Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: 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 626-870, Republic of Korea. Electronic address: 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 626-870, Republic of Korea. Electronic address: hagis@pusan.ac.kr.
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 626-870, Republic of Korea; Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: jung0603@pusan.ac.kr.
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Jung
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced* / Q000188:drug therapy*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011897:Random Allocation; D032141:Schisandra / Q000737:chemistry*; D013312:Stress, Physiological / Q000187:drug effects*; D014415:Tunicamycin / Q000633:toxicity
chemical_list: D004041:Dietary Fats; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D010936:Plant Extracts; D014415:Tunicamycin
keywords: Endoplasmic reticulum stress; Inflammation; Lipogenesis; Nonalcoholic fatty liver disease; Schisandra chinensis; Triglyceride accumulation