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10.1038/s41401-018-0189-1 http://scihub22266oqcxt.onion/10.1038/s41401-018-0189-1 C6786373!6786373!30617294     free     free     free Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Acta+Pharmacol+Sin 2019 ; 40 (7): 867-78 Nephropedia Template TP {{tp|p=30617294|t=2019. Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway |pdf=|usr=}}{{30617294}} gab.com Text Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway JO: Acta Pharmacol Sin http://www.kidney.de/pget.php?&tw=1&pmid=30617294 #FOAvip 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, 1??g/mL). We showed that pretreatment with MLB (10?100??M) dose-dependently inhibited LPS-induced upregulation of inflammatory cytokines ICAM1, VCAM1, and TNF?, which contributed to reduced leukocytes adhesion and attenuation of endothelial hyperpermeability in HMEC-1 cells. SD rats were injected with LPS (10?mg/kg, ip) to induce endothelial dysfunction in vivo. We showed that pretreatment with MLB (25?100?mg/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-?B activation through inhibition of I?B? degradation and subsequent phosphorylation of NF-?B 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 I?B? degradation and ICAM1 up-regulation, which were mimicked by PKC inhibition (Gö6983) or PI3K/Akt inhibition (LY294002). In summary, our results demonstrate that MLB inhibits NF-?B 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. Twit Text FOAVip Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway ????Acta Pharmacol Sin http://www.kidney.de/pget.php?&tw=1&pmid=30617294 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=30617294 #FOAvip English Wikipedia <ref>{{Cite pmid|30617294}}</ref> Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway #MMPMID30617294 Gao F; Li Jm; Xi C; Li Hh; Liu Yl; Wang Yp; Xuan Lj Acta Pharmacol Sin 2019[Jul]; 40 (7): 867-78 PMID30617294show ga 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, 1??g/mL). We showed that pretreatment with MLB (10?100??M) dose-dependently inhibited LPS-induced upregulation of inflammatory cytokines ICAM1, VCAM1, and TNF?, which contributed to reduced leukocytes adhesion and attenuation of endothelial hyperpermeability in HMEC-1 cells. SD rats were injected with LPS (10?mg/kg, ip) to induce endothelial dysfunction in vivo. We showed that pretreatment with MLB (25?100?mg/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-?B activation through inhibition of I?B? degradation and subsequent phosphorylation of NF-?B 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 I?B? degradation and ICAM1 up-regulation, which were mimicked by PKC inhibition (Gö6983) or PI3K/Akt inhibition (LY294002). In summary, our results demonstrate that MLB inhibits NF-?B 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. äMagnesium lithospermate B protects the endothelium from inflammation-i(epmc).pdf DeepDyve Pubget Overpricing