The protective effect of Luteolin on myocardial ischemia/reperfusion (I/R) injury through TLR4/NF-κB/NLRP3 inflammasome pathway

Xu Zhang, Qianming Du, Yan Yang, Jianing Wang, Shuai Dou, Chao Liu, Junguo Duan
Biomedicine & Pharmacotherapy 2017, 91: 1042-1052
The purpose of the present study was to investigate the effect of Luteolin(Lut) on myocardial ischemia reperfusion injury and explore the underlying mechanism. Myocardial ischemia reperfusion injury (I/R) model was induced with 30min of left anterior descending (LAD) occlusion followed by 24h of reperfusion. In vivo, the rats were randomly divided into 5 groups: (1)Sham, (2)I/R, (3)I/R+Lut(40mg/kg), (4)I/R+Lut(80mg/kg) and (5)I/R+Lut(160mg/kg). In vitro, the H9c2 cells were assigned to five groups: (1)control, (2)hypoxia-reoxygenation(H/R), (3)H/R+Lut(5μM), (4)H/R+Lut(10μM) and (5)H/R+Lut(20μM). The H9c2 cells were stimulated with H/R protocol in the presence or absence of TAK-242, a TLR4 inhibitor. As a result, Lut ameliorated myocardial ischemia reperfusion injury and hypoxia-reoxygenation as evidenced by triphenyl tetrazolium chloride (TTC) staining and MTT assay, respectively. Lut was founded to decrease the levels of aspartate transaminase(AST), creatine phosphokinase-isoenzyme (CK-MB) and lactate dehydrogenase (LDH) in serum. Moreover, Lut could reduce the contents of interleukin-1β(IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in serum of rats and supernant of H9c2 cells. In addition, Lut remarkably downregulated the expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NF-κB). Lut also inhibited the upregulations of inflammasome components, such as NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC) in I/R-induced rats and H/R-induced H9c2 cells. In conclusion, Lut exhibited strong favorable cardioprotective effect on myocardial I/R injury which might be related to the down-regulation of the TLR4-meidated NF-κB/NLRP3 inflammasome in vivo and in vitro.

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