Multi-Target Cardioprotective Potential of Ajuga bracteosa Phytochemicals: An Integrated Network Pharmacology and Molecular Docking Approach

Background: Myocardial infarction (MI), especially its adrenaline-induced myocardial injury, remains a leading cause of global mortality, often resulting in irreversible cardiac damage and heart failure due to stress cardiomyopathy. Objectives: Wall. ex Benth. (Lamiaceae). It is a medicinal plant used in the Himalayas for a long time in folk medicine for heart diseases, hypertension, and inflammatory diseases. Studies have reported the antioxidant and anti-inflammatory ability of its crude extracts. However, the active phytochemicals and their multi-target molecular mechanisms against adrenaline-induced MI remain unclear. Design: phytochemicals. Method: Thirty bioactive compounds from the whole plant were identified. Of these, eight lead phytochemicals, including neo-clerodane diterpenoids and phytoecdysteroids, were subjected to ADMET screening. They passed the screening showing desirable drug-like properties. From network pharmacology analysis, 278 overlapping targets were identified between MI-associated genes and those in the ingredient database. The top three hub proteins were AKT1 (node degree 151), GAPDH (150), and TNF (149), respectively. Results: GO and KEGG enrichment analyses showed that these genes were primarily involved in the regulation of the apoptotic process, oxidant stress response, and the PI3K-Akt, TNF, and MAPK signaling pathways. Molecular docking (MOE 2019.01) results show that Ivain II showed the strongest binding affinity score with value of -9.42 kcal/mol for GAPDH and TNF-α through multiple hydrogen bonds, lipophilic contacts, and π-alkyl interactions. Conclusion: and identify Ivain II, 20-Hydroxyecdysone, and Ajugalactone as promising lead compounds warranting further experimental validation.