PMID- 26972505 OWN - NLM STAT- MEDLINE DCOM- 20170224 LR - 20211204 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 185 DP - 2016 Jun 5 TI - Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress. PG - 96-104 LID - S0378-8741(16)30126-X [pii] LID - 10.1016/j.jep.2016.03.021 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIAL AND 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. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Jang, Min-Kyung AU - Jang MK AD - 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. FAU - Nam, Jeong Soo AU - Nam JS AD - 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. FAU - Kim, Ji Ha AU - Kim JH AD - 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. FAU - Yun, Ye-Rang AU - Yun YR AD - 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. FAU - Han, Chang Woo AU - Han CW AD - Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. Electronic address: yeast10@hanmail.net. FAU - Kim, Byung Joo AU - Kim BJ AD - 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. FAU - Jeong, Han-Sol AU - Jeong HS AD - 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. FAU - Ha, Ki-Tae AU - Ha KT AD - 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. FAU - Jung, Myeong Ho AU - Jung MH AD - 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. LA - eng PT - Journal Article DEP - 20160310 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Dietary Fats) RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (HSPA5 protein, human) RN - 0 (Hspa5 protein, mouse) RN - 0 (Plant Extracts) RN - 11089-65-9 (Tunicamycin) SB - IM MH - Animals MH - Dietary Fats/administration & dosage/adverse effects MH - Endoplasmic Reticulum/*drug effects MH - Endoplasmic Reticulum Chaperone BiP MH - Hep G2 Cells MH - Humans MH - Lipid Metabolism/drug effects MH - Liver/drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Non-alcoholic Fatty Liver Disease/*chemically induced/*drug therapy MH - Plant Extracts/chemistry/*pharmacology MH - Random Allocation MH - Schisandra/*chemistry MH - Stress, Physiological/*drug effects MH - Tunicamycin/toxicity OTO - NOTNLM OT - Endoplasmic reticulum stress OT - Inflammation OT - Lipogenesis OT - Nonalcoholic fatty liver disease OT - Schisandra chinensis OT - Triglyceride accumulation EDAT- 2016/03/15 06:00 MHDA- 2017/02/25 06:00 CRDT- 2016/03/15 06:00 PHST- 2015/10/07 00:00 [received] PHST- 2016/01/20 00:00 [revised] PHST- 2016/03/10 00:00 [accepted] PHST- 2016/03/15 06:00 [entrez] PHST- 2016/03/15 06:00 [pubmed] PHST- 2017/02/25 06:00 [medline] AID - S0378-8741(16)30126-X [pii] AID - 10.1016/j.jep.2016.03.021 [doi] PST - ppublish SO - J Ethnopharmacol. 2016 Jun 5;185:96-104. doi: 10.1016/j.jep.2016.03.021. Epub 2016 Mar 10.