PMID- 30394648 OWN - NLM STAT- MEDLINE DCOM- 20200415 LR - 20210109 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 23 IP - 1 DP - 2019 Jan TI - Picroside II attenuates hyperhomocysteinemia-induced endothelial injury by reducing inflammation, oxidative stress and cell apoptosis. PG - 464-475 LID - 10.1111/jcmm.13949 [doi] AB - Picroside II (P-II), one of the main active components of scrophularia extract, which have anti-oxidative, anti-inflammatory effects, but its effect on hyperhomocysteinemia (HHcy) induced endothelial injury remains to be determined. Here, we test whether P-II protects HHcy-induced endothelial dysfunction against oxidative stress, inflammation and cell apoptosis. In vitro study using HUVECs, and in hyperhomocysteinemia mouse models, we found that HHcy decreased endothelial SIRT1 expression and increased LOX-1 expression, subsequently causing reactive oxygen species generation, up-regulation of NADPH oxidase activity and NF-kappaB activation, thereby promoting pro-inflammatory response and cell apoptosis. Blockade of Sirt1 with Ex527 or siRNASIRT1 increased LOX-1 expression, whereas overexpression of SIRT1 decreased LOX-1 expression markedly. P-II treatment significantly increased SIRT1 expression and reduced LOX-1 expression, and protected against endothelial cells from Hcy-induced oxidative injury, inflammation and apoptosis. However, blockade of SIRT1 or overexpression of LOX-1 attenuated the therapeutic effects of P-II. In conclusion, our results suggest that P-II prevents the Hcy induced endothelial damage probably through regulating the SIRT1/LOX-1 signaling pathway. CI - (c) 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. FAU - Wang, Yunkai AU - Wang Y AUID- ORCID: 0000-0002-2979-1569 AD - Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Hong, Yajun AU - Hong Y AD - Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China. FAU - Zhang, Chunyu AU - Zhang C AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Shen, Yunli AU - Shen Y AD - Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Pan, Ye Shen AU - Pan YS AD - Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Chen, Rui Zhen AU - Chen RZ AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Zhang, Qi AU - Zhang Q AD - Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Chen, Yi Han AU - Chen YH AD - Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181105 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Antioxidants) RN - 0 (Cinnamates) RN - 0 (Iridoid Glucosides) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 39012-20-9 (picroside II) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Animals MH - Antioxidants/metabolism MH - Apoptosis/*drug effects MH - Cell Line MH - Cinnamates/*pharmacology MH - Endothelium/*drug effects/metabolism MH - Human Umbilical Vein Endothelial Cells/drug effects/metabolism MH - Humans MH - Hyperhomocysteinemia/*drug therapy/metabolism MH - Inflammation/*drug therapy/metabolism MH - Iridoid Glucosides/*pharmacology MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/metabolism MH - Oxidative Stress/*drug effects MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/drug effects MH - Sirtuin 1/metabolism MH - Up-Regulation/drug effects PMC - PMC6307770 OTO - NOTNLM OT - LOX-1 OT - Picroside II OT - SIRT1 OT - atherosclerosis OT - hyperhomocysteinemia OT - oxidative stress EDAT- 2018/11/06 06:00 MHDA- 2020/04/16 06:00 PMCR- 2019/01/01 CRDT- 2018/11/06 06:00 PHST- 2018/05/27 00:00 [received] PHST- 2018/09/03 00:00 [accepted] PHST- 2018/11/06 06:00 [pubmed] PHST- 2020/04/16 06:00 [medline] PHST- 2018/11/06 06:00 [entrez] PHST- 2019/01/01 00:00 [pmc-release] AID - JCMM13949 [pii] AID - 10.1111/jcmm.13949 [doi] PST - ppublish SO - J Cell Mol Med. 2019 Jan;23(1):464-475. doi: 10.1111/jcmm.13949. Epub 2018 Nov 5.