Mechanism of silibinin derivative Sil-1 modulating MAPK signaling pathway to inhibit acute myocardial infarction in rats
- VernacularTitle:水飞蓟宾衍生物Sil-1调控MAPK信号通路抑制大鼠急性心肌梗死损伤的机制
- Author:
Yi-fan LIU
1
;
Meng LI
;
De-yu CUI
;
Xiao-yan LU
;
Ting-bo NING
;
Chun-xiu XU
;
Jing-chun YAO
;
Ji-dong ZHOU
;
Zhong LIU
Author Information
- Publication Type:Journal Article
- Keywords: silibinin; acute myocardial ischemia; in-flammation; oxidative stress; proteomics; MAPK sig-naling pathway
- From: Chinese Pharmacological Bulletin 2025;41(8):1453-1462
- CountryChina
- Language:Chinese
- Abstract: Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.
