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

Ajuga bracteosa 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

The current study investigated the predicted cardioprotective potential of A. bracteosa, uses integrated network pharmacology, ADMET profiling, and molecular docking to investigate A. bracteosa 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

These findings provide the first computational mechanistic insight into the predicted multi-target cardioprotective potential of A. bracteosa and identify Ivain II, 20-Hydroxyecdysone, and Ajugalactone as promising lead compounds warranting further experimental validation.