Investigation of Berberine's Cardioprotective Effects and Its Association With the Notch Signaling Pathway in Rat Myocardial Ischemia-Reperfusion Injury.
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Abstract
Background: Ischemia-reperfusion injury poses a significant challenge in cardiac pathology, leading to myocardial cell damage and dysfunction. Berberine, a natural compound, has shown potential cardioprotective effects. This study aims to investigate the protective role of berberine in myocardial cells post-ischemia-reperfusion injury, focusing on its modulation of the Neurogenic locus notch homolog protein (Notch) signaling pathway.
Methods: Male rats were subjected to ischemia-reperfusion injury and treated with berberine. Triphenyltetrazolium chloride (TTC) and hematoxylin and eosin (HE) staining were used to assess myocardial tissue damage and structure. Gene expression of Neurogenic locus notch homolog protein 1 (Notch1), Hairy and enhancer of split-1 (Hes1), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) was analyzed using Quantitative Polymerase Chain Reaction (qPCR). Apoptosis rate in myocardial cells was evaluated using Terminal deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) staining. Protein expression of Bcl-2 and Bax was examined. Molecular docking and Microscale Thermophoresis (MST) validation were performed to investigate the interaction between berberine and Notch1.
Results: Berberine treatment was associated with effective protection of myocardial tissue post-ischemia-reperfusion, indicated by reduced infarct area (p < 0.05) and improvements in tissue structure. Coinciding with these observations, berberine also influenced the expression of Notch1, Hes1, Bcl-2, and Bax in myocardial tissue, alongside modulation of Bcl-2 and Bax protein levels (p < 0.05). Additionally, molecular studies revealed that berberine binds to Notch1, suggesting a potential interaction.
Conclusion: The study suggests an association between berberine's cardioprotective effects and Notch signaling pathway modulation in the context of myocardial ischemia-reperfusion injury. While berberine was found to bind Notch1 and affect gene and protein expression related to apoptosis, further research is necessary to determine whether these effects directly contribute to reduced apoptosis and enhanced cell survival.
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