Hydroxysafflor yellow A attenuates LPS-induced myocardial injury by targeting MD2
Objective To investigate whether Hydroxysafflor yellow A(HSYA)can target myeloid differentiation factor 2(MD2)to alleviate inflammation and apoptosis in mouse cardiomyocytes induced by lipopolysaccharide(LPS).Methods Mouse ventricular myocytes were pretreated with different concentrations of HSYA(0.1 μmol/L,1 μmol/L,10 μmol/L)for 2 hours,followed by LPS(5 μg/mL)intervention for 4 hours before detection.Molecular docking technology was fur-ther used to determine the binding mode and binding site of HSYA with MD2.The effect of HSYA on the generation of TLR4/MD2 complexes was detected by immunoprecipitation,and the mechanism of action was explored by Western blot-ting.Results Compared with the control group,LPS induced apoptosis in cardiomyocytes,promoted the release of reactive oxygen species(ROS)within the cells and the mitochondria,and facilitated the release of the inflammatory factor interleu-kin-6(IL-6),but without significant changes in interleukin-1β(IL-1β)and tumor necrosis factor α(TNF-α).Compared with the LPS-induced group,HSYA effectively reduced LPS-induced cardiomyocyte apoptosis,ROS release,and inflammatory factor damage.Molecular docking results suggested that HSYA could bind to the hydrophobic pocket of MD2,and HSYA could dose-dependently reduce the generation of TLR4/MD2 complexes,indicating that HSYA competitively binds to MD2 protein with TLR4.The results of TLR4,MD2,and phosphorylated NF-κB p65 protein expressions via Western blotting showed that HSYA lowered the expression of LPS-induced TLR4 and MD2,phosphorylated NF-κB p65 proteins in a con-centration-dependent manner.Conclusion HSYA can target MD2 and alleviate LPS-induced inflammatory damage through mediation of the TLR4/MD2 complex,playing a role in reducing inflammatory damage and apoptosis in cardiomyocytes.
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维普
