Effect of Guanxinkang on ox-LDL and LPS induced ferroptosis in macrophages by acti-vating ERK5/Nrf2 pathway
Objective To investigate the effect of Guanxinkang on lipopolysaccharide(LPS)and oxidized low-density lipopro-tein(ox-LDL)induced ferroptosis in macrophages and its anti-atherosclerosis mechanism.Methods ox-LDL combined with LPS was used to induce iron death in RAW264.7 macrophages,and Guanxinkang and ERK5 inhibitor XMD8-92 were adminis-tered to intervene,and the levels of lipid peroxides(LPO),intracellular ferric ion(Fe2+),reactive oxygen species(ROS)and glutathione(GSH)related indexes of iron death were detected.IL-6,TNF-α,MMP and ERK5/Nrf2 signaling pathway mRNA and protein expression.Results In RAW264.7 macrophages,LPO content,intracellular Fe2+content and ROS level increased,GSH content decreased,IL-6,TNF-α,MMP-2 and MMP-9 contents increased significantly after LPS combined with ox-LDL induction.mRNA levels of ERK5,Nrf2,HO-1 and GPX-4 and protein expression levels of P-erk5,p-nrF2 and HO-1 were decreased(P＜0.05).In Guanxinkang group,LPO,Fe2+and ROS were decreased,GSH content was increased,IL-6,TNF-α,MMP-2 and MMP-9 levels were decreased,ERK5,Nrf2,HO-1 and GPX-4 mRNA and p-ERK5,p-Nrf2 and HO-1 protein expression levels were increased.XMD8-92 could inhibit the effect of Guanxinkang(P＜0.05).Conclusion Guanxinkang can inhibit the ferroptosis of RAW264.7 macrophages induced by LPS and ox-LDL,and reduce the inflammatory response.The mechanism is related to the activation of ERK5 and downstream Nrf2 pathway.
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