Study On The Protective Effect Of Pomegranate Peel And Its Effective Component Ellagic Acid On H9c2 Cells Damaged By Hypoxia

Objective:(1)Network pharmacology and molecular docking methods were used to study the multi-component,multi-target and multi-pathway mechanism of pomegranate peel and its active ingredient ellagic acid in the intervention of altitude disease.(2)Detect the protective effect of pomegranate peel and ellagic acid on hypoxia injury of H9c2 myocardial cells,and explore its effect on apoptosis and its related molecular mechanism..Method:(1)Through TCMSP database and related documents,the active components and target of action of pomegranate peel were searched and screened,The related targets of highland disease and pomegranate peel were screened and the protein interaction diagram was established.GO and KEGG pathway enrichment and molecular docking were studied.(2)The antiapoptotic effect of pomegranate peel and the effects of ellagic acid on cell proliferation,reactive oxygen species,mitochondrial membrane potential and apoptosis were detected by basic experiments.(3)Western-blot was used to detect the effect of ellagic acid on the expression of apoptotic protein bax and bcl-2.Result:(1)Nine active ingredients were obtained from pomegranate peel,among which ellagic acid was one of the most important active ingredients.(2)The key targets of KEGG enrichment analysis were mainly enriched in biological processes such as ribosome and apoptosis.(3)Molecular docking results showed that the core compounds in pomegranate peel had strong binding activity to the main targets.(4)Pomegranate peel has antiapoptotic effect on hypoxic injury of H9c2 cardiomyocytes.(5)Ellagic acid can promote proliferation,inhibit apoptosis,reduce ROS level and maintain mitochondrial membrane potential in H9c2 cardiomyocytes induced by hypoxia.(6)The anti-apoptotic effect of ellagic acid on hypoxic injury of H9c2 cardiomyocytes may be realized through the Bcl-2 protein family.Conclusion: Based on the network pharmacology,the characteristics of pomegranate peel in the intervention of multi-component-multitarget-multi-passage of High altitude disease were discussed.Pomegranate peel intervened in High altitude disease through the biological processes of ribosome,cell apoptosis and other key targets,ellagic acid is one of the most important active ingredients in pomegranate peel,Pomegranate peel and ellagic acid have potential value in the prevention and treatment of plateau disease.