Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway | |
Gao, Fei1,2; Li, Jiao-Meng1,2; Xi, Cong1,2; Li, Hui-Hui1,2; Liu, Ying-Luo1,2; Wang, Yi-Ping1; Xuan, Li-Jiang1,2 | |
刊名 | Acta pharmacologica Sinica |
2019-01-07 | |
关键词 | Nrf2 Pi3k/akt Pkc Endothelium Human Dermal Microvascular Endothelial Cells Inflammation Lipopolysaccharide Magnesium Lithospermate b Rat Superior Mesenteric Artery Rings |
DOI | 10.1038/s41401-018-0189-1 |
英文摘要 | Magnesium lithospermate B (MLB) is an active component of Salvia miltiorrhiza Radix, a traditional Chinese herb used in treating cardiovascular diseases. In this study, we investigated the protective effects of MLB against inflammation-induced endothelial dysfunction in vitro and in vivo, and the underlying mechanisms. Endothelial dysfunction was induced in human dermal microvascular endothelial cells (HMEC-1) in vitro by lipopolysaccharide (LPS, 1mug/mL). We showed that pretreatment with MLB (10-100muM) dose-dependently inhibited LPS-induced upregulation of inflammatory cytokines ICAM1, VCAM1, and TNFalpha, which contributed to reduced leukocytes adhesion and attenuation of endothelial hyperpermeability in HMEC-1 cells. SD rats were injected with LPS (10mg/kg, ip) to induce endothelial dysfunction in vivo. We showed that pretreatment with MLB (25-100mg/kg, ip) dose-dependently restored LPS-impaired endothelial-dependent vasodilation in superior mesenteric artery (SMA), attenuated leukocyte adhesion in mesenteric venules and decreased vascular leakage in the lungs. We further elucidated the mechanisms underlying the protective effects of MLB, and revealed that MLB pretreatment inhibited NF-kappaB activation through inhibition of IkappaBalpha degradation and subsequent phosphorylation of NF-kappaB p65 in vitro and in vivo. In HMEC-1 cells, MLB pretreatment activated the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. Knockdown of Nrf2 with siRNA abolished the inhibitory effects of MLB on IkappaBalpha degradation and ICAM1 up-regulation, which were mimicked by PKC inhibition (Go6983) or PI3K/Akt inhibition (LY294002). In summary, our results demonstrate that MLB inhibits NF-kappaB activation through PKC- and PI3K/Akt-mediated Nrf2 activation in HMEC-1 cells and protects against LPS-induced endothelial dysfunction in murine model of acute inflammation. |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/279953] |
专题 | 药理学第一研究室 上海中药现代化研究中心 |
通讯作者 | Xuan, Li-Jiang |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, 201203, Peoples R China. 2.Univ Chinese Acad Sci, School of Pharmacy, Beijing, 100049, Peoples R China. |
推荐引用方式 GB/T 7714 | Gao, Fei,Li, Jiao-Meng,Xi, Cong,et al. Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway[J]. Acta pharmacologica Sinica,2019. |
APA | Gao, Fei.,Li, Jiao-Meng.,Xi, Cong.,Li, Hui-Hui.,Liu, Ying-Luo.,...&Xuan, Li-Jiang.(2019).Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway.Acta pharmacologica Sinica. |
MLA | Gao, Fei,et al."Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway".Acta pharmacologica Sinica (2019). |
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