PMID- 28905500 OWN - NLM STAT- MEDLINE DCOM- 20180710 LR - 20220410 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 21 IP - 12 DP - 2017 Dec TI - Salidroside suppressing LPS-induced myocardial injury by inhibiting ROS-mediated PI3K/Akt/mTOR pathway in vitro and in vivo. PG - 3178-3189 LID - 10.1111/jcmm.12871 [doi] AB - The purpose of the present study was to investigate the effect of salidroside (Sal) on myocardial injury in lipopolysaccharide (LPS)-induced endotoxemic in vitro and in vivo. SD rats were randomly divided into five groups: control group, LPS group (15 mg/kg), LPS plus dexamethasone (2 mg/kg), LPS plus Sal groups with different Sal doses (20, 40 mg/kg). Hemodynamic measurement and haematoxylin and eosin staining were performed. Serum levels of creatine kinase (CK), lactate dehydrogenase, the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), glutathione, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta) were measured after the rats were killed. iNOS, COX-2, NF-kappaB and PI3K/Akt/mTOR pathway proteins were detected by Western blot. In vitro, we evaluated the protective effect of Sal on rat embryonic heart-derived myogenic cell line H9c2 induced by LPS. Reactive oxygen species (ROS) in H9c2 cells was measured by flow cytometry, and the activities of the antioxidant enzymes CAT, SOD, GSH-px, glutathione-S-transferase, TNF-alpha, IL-6 and IL-1beta in cellular supernatant were measured. PI3K/Akt/mTOR signalling was examined by Western blot. As a result, Sal significantly attenuated the above indices. In addition, Sal exerts pronounced cardioprotective effect in rats subjected to LPS possibly through inhibiting the iNOS, COX-2, NF-kappaB and PI3K/Akt/mTOR pathway in vivo. Furthermore, the pharmacological effect of Sal associated with the ROS-mediated PI3K/Akt/mTOR pathway was proved by the use of ROS scavenger, N-acetyl-l-cysteine, in LPS-stimulated H9C2 cells. Our results indicated that Sal could be a potential therapeutic agent for the treatment of cardiovascular disease. CI - (c) 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. FAU - Chen, Lvyi AU - Chen L AD - School of Pharmacy, South-Central University for Nationalities, Wuhan, China. FAU - Liu, Peng AU - Liu P AD - School of Pharmacy, South-Central University for Nationalities, Wuhan, China. FAU - Feng, Xin AU - Feng X AD - Institute of Tibetan Medicine, China Tibetology Research Center, Beijing, China. FAU - Ma, Chunhua AU - Ma C AD - Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, China. LA - eng PT - Journal Article DEP - 20170914 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Cardiotonic Agents) RN - 0 (Glucosides) RN - 0 (IL1B protein, rat) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Phenols) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Necrosis Factor-alpha) RN - 7S5I7G3JQL (Dexamethasone) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - GAN16C9B8O (Glutathione) RN - M983H6N1S9 (rhodioloside) SB - IM MH - Animals MH - Cardiotonic Agents/*pharmacology MH - Catalase/genetics/metabolism MH - Cell Line MH - Dexamethasone/pharmacology MH - Endotoxemia/chemically induced/*drug therapy/genetics/pathology MH - Gene Expression Regulation MH - Glucosides/*pharmacology MH - Glutathione/metabolism MH - Glutathione Peroxidase/genetics/metabolism MH - Hemodynamics/drug effects MH - Interleukin-1beta/genetics/metabolism MH - Interleukin-6/genetics/metabolism MH - Lipopolysaccharides MH - Myocardial Reperfusion Injury/chemically induced/*drug therapy/genetics/pathology MH - Myocardium/metabolism/pathology MH - Myocytes, Cardiac/drug effects/metabolism/pathology MH - Nitric Oxide Synthase Type II/genetics/metabolism MH - Phenols/*pharmacology MH - Phosphatidylinositol 3-Kinases/*genetics/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/antagonists & inhibitors/metabolism MH - Signal Transduction MH - Superoxide Dismutase/genetics/metabolism MH - TOR Serine-Threonine Kinases/antagonists & inhibitors/*genetics/metabolism MH - Tumor Necrosis Factor-alpha/genetics/metabolism PMC - PMC5706507 OTO - NOTNLM OT - LPS OT - ROS OT - H9C2 OT - PI3K/Akt/mTOR OT - myocardial injury OT - salidroside EDAT- 2017/09/15 06:00 MHDA- 2018/07/11 06:00 PMCR- 2017/12/01 CRDT- 2017/09/15 06:00 PHST- 2015/11/09 00:00 [received] PHST- 2016/03/12 00:00 [accepted] PHST- 2017/09/15 06:00 [pubmed] PHST- 2018/07/11 06:00 [medline] PHST- 2017/09/15 06:00 [entrez] PHST- 2017/12/01 00:00 [pmc-release] AID - JCMM12871 [pii] AID - 10.1111/jcmm.12871 [doi] PST - ppublish SO - J Cell Mol Med. 2017 Dec;21(12):3178-3189. doi: 10.1111/jcmm.12871. Epub 2017 Sep 14.