PMID- 28512854 OWN - NLM STAT- MEDLINE DCOM- 20171004 LR - 20181202 IS - 1099-1573 (Electronic) IS - 0951-418X (Linking) VI - 31 IP - 7 DP - 2017 Jul TI - Mogroside IIIE Attenuates LPS-Induced Acute Lung Injury in Mice Partly Through Regulation of the TLR4/MAPK/NF-kappaB Axis via AMPK Activation. PG - 1097-1106 LID - 10.1002/ptr.5833 [doi] AB - Acute lung injury (ALI) often leads to high mortality, and there is as yet no effective drug treatment. The present study aimed to investigate protective effects of mogroside IIIE (MGIIIE, a cucurbitane-type triterpenoid from Siraitia grosvenorii Fruits) in experimental ALI and its underlying mechanism. MGIIIE (1, 10 0r 20 mg/kg) was orally administered for 1 h before a single intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg). MGIIIE treatment dose-dependently suppressed pulmonary oedema, pro-inflammatory mediators (IL-1beta, IL-6, TNF-alpha and HMGB1) release and higher MPO activity in lung tissues induced by LPS challenge. Molecular researches showed that mogroside IIIE (20 mg/kg) not only increased the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) but suppressed the over-expression of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In addition, MGIIIE also inhibited the activation of MAPKs and nuclear factor kappaB (NF-kappaB) signalling in lung tissues from LPS-challenged mice. Similar antiinflammatory effects of MGIIIE were obtained in LPS-treated macrophages. Compound C (a pharmacological AMPK inhibitor) obviously reversed the antiinflammatory effect of MGIIIE in LPS-induced ALI mice. Taken together, AMPK activation plays a crucial role in the antiinflammatory effects of MGIIIE in LPS-induced ALI by down-regulating TLR4/MAPK/NF-kappaB signalling pathways. Copyright (c) 2017 John Wiley & Sons, Ltd. CI - Copyright (c) 2017 John Wiley & Sons, Ltd. FAU - Tao, Lijun AU - Tao L AD - Research Department of Pharmacognosy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. FAU - Cao, Fengyan AU - Cao F AD - Research Department of Pharmacognosy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. FAU - Xu, Gonghao AU - Xu G AD - Research Department of Pharmacognosy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. FAU - Xie, Haifeng AU - Xie H AD - Chengdu Biopurity Chengdu Biopurity Phytochemicals Ltd, Chengdu, 611131, People's Republic of China. FAU - Zhang, Mian AU - Zhang M AUID- ORCID: 0000-0002-1504-305X AD - Research Department of Pharmacognosy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. FAU - Zhang, Chaofeng AU - Zhang C AD - Research Department of Pharmacognosy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. LA - eng PT - Journal Article DEP - 20170517 PL - England TA - Phytother Res JT - Phytotherapy research : PTR JID - 8904486 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Glucosides) RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, mouse) RN - 0 (IL1B protein, mouse) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (Triterpenes) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (interleukin-6, mouse) RN - 0 (mogroside IIIE) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Acute Lung Injury/chemically induced/*drug therapy MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Down-Regulation MH - Glucosides/*pharmacology MH - HMGB1 Protein MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Lipopolysaccharides MH - Lung/drug effects MH - Macrophages/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/*metabolism MH - Myeloid Differentiation Factor 88/metabolism MH - NF-kappa B/*metabolism MH - Phosphorylation MH - Signal Transduction/drug effects MH - Toll-Like Receptor 4/*metabolism MH - Triterpenes/*pharmacology MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - AMPK OT - TLR4 OT - acute lung injury OT - lipopolysaccharide OT - mogroside IIIE EDAT- 2017/05/18 06:00 MHDA- 2017/10/05 06:00 CRDT- 2017/05/18 06:00 PHST- 2017/01/22 00:00 [received] PHST- 2017/03/24 00:00 [revised] PHST- 2017/04/19 00:00 [accepted] PHST- 2017/05/18 06:00 [pubmed] PHST- 2017/10/05 06:00 [medline] PHST- 2017/05/18 06:00 [entrez] AID - 10.1002/ptr.5833 [doi] PST - ppublish SO - Phytother Res. 2017 Jul;31(7):1097-1106. doi: 10.1002/ptr.5833. Epub 2017 May 17.