Over the last five years, 80% of cardiovascular disease (CVD) mortalities transpired in developing nations, particularly in the Middle East and Indian Subcontinent. In 2022, CVDs culminated in approximately 19.8 million demises, with myocardial infarction (MI) accountable for 9 to 10 million. Affective Disorder (AD) is frequently overlooked in the framework of MI. Investigations have substantiated a bidirectional relationship between AD and MI, with severe AD confront a 40%-60% augmented risk of developing CVD and experiencing MI. The neurocardiovascular axis is critical for maintaining homeostasis during ischemic stress. Hypoxia-Inducible Factor-1 alpha (HIF-1α) serves as a master regulator of adaptive responses in neuronal and cardiac tissues. This study identifies potent phytocompounds from traditional Ayurvedic formulations as dual system modulators using an integrated computational framework.
Background: Over the last five years, 80% of cardiovascular disease (CVD) mortalities transpired in developing nations, particularly in the Middle East and Indian Subcontinent. In 2022, CVDs culminated in approximately 19.8 million demises, with myocardial infarction (MI) accountable for 9 to 10 million. Affective Disorder (AD) is frequently overlooked in the framework of MI. Investigations have substantiated a bidirectional relationship between AD and MI, with severe AD confront a 40%-60% augmented risk of developing CVD and experiencing MI. The neurocardiovascular axis is critical for maintaining homeostasis during ischemic stress. Hypoxia-Inducible Factor-1 alpha (HIF-1α) serves as a master regulator of adaptive responses in neuronal and cardiac tissues. This study identifies potent phytocompounds from traditional Ayurvedic formulations as dual system modulators using an integrated computational framework.
Methods: Ethnobotanical leads were selected from the Sushruta Samhita, with phytochemical profiles retrieved via IMPPAT. Disease-associated proteins for MI and AD were intersected with CoCl2-stabilized hypoxic proteins (CTD Database) to isolate a core "hypoxic-stress" interactome. Protein-protein interaction (PPI) networks were analyzed in Cytoscape (cytoHubba) to identify hub genes. Molecular docking assessed binding affinities against HIF-1α and other hubs. Structural stability was validated via CABS-flex 3.0 RMSF analysis.
Results: Initial screening of 2,300 compounds identified 246 lead compounds with high GI absorption, BBB permeation, and adherence to Lipinski, Veber, Egan, Muegge, and Ghose rules. Network analysis identified HIF-1α as a primary node among 10 key hub genes. Molecular docking of 248 compounds (including 2 controls Aspirin and Baicalin) against the 10 hubs was evaluated using Relative Binding Affinity (RBA) to integrate MI and AD efficacy. Toxicity filtering via ProTox 3.0 further refined the selection from 81 candidates to 24 final leads. These lead compounds demonstrated higher RBA than synthetic stabilizers. CABS-flex simulations confirmed structural stability with fluctuations in critical binding residues thereby anaylzing expression.
Conclusions: Our in silico findings suggest that the identified phytocompounds act as effective neurocardiovascular stabilizers by modulating the HIF-1α pathway. Our multi-target approach provides a validated roadmap for future pre-clinical validation in hypoxic models, offering a traditional alternative to conventional pharmacotherapy.
Mr Jatin Gupta1, Prof Pammi Gauba1, Prof Vibha Rani1 1Jaypee Institute Of Information Technololgy, Noida, India
Over the last five years, 80% of cardiovascular disease (CVD) mortalities transpired in developing nations, particularly in the Middle East and Indian Subcontinent. In 2022, CVDs culminated in approximately 19.8 million demises, with myocardial infarction (MI) accountable for 9 to 10 million. Affective Disorder (AD) is frequently overlooked in the framework of MI. Investigations have substantiated a bidirectional relationship between AD and MI, with severe AD confront a 40%-60% augmented risk of developing CVD and experiencing MI. The neurocardiovascular axis is critical for maintaining homeostasis during ischemic stress. Hypoxia-Inducible Factor-1 alpha (HIF-1α) serves as a master regulator of adaptive responses in neuronal and cardiac tissues. This study identifies potent phytocompounds from traditional Ayurvedic formulations as dual system modulators using an integrated computational framework.
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