In silico exploration of bioactive compounds from Acorus calamus L. for targeted treatment of ischemic heart disease: Molecular insights and therapeutic prospects

Abstract

Abstract BACKGROUND: Ischemic heart disease (IHD) accounts for 80%–85% of mortality, highlighting the need to develop effective and noninvasive management strategies. Lekhana karma (therapeutic scrapping) helps in balancing the imbalanced Kapha and Medodhatu, which are important factors in the pathogenesis of IHD. Vacha—Acorus calamus Linn (AC) is 1 of the 10 Lekhaneeya drugs described in Charaka Samhita and is widely available and cost-effective. However, its bioactive phytoconstituents’ mode of action and molecular entities remain unexplored. Hence, this study aimed to elucidate the mode of action of its bioactive compounds and their interaction with IHD disease targets and pathways. METHODS: Phytochemicals from AC were collected, followed by screening of bioactive phytochemicals, collecting gene identifications, and pathways related to IHD. Later, common compounds and pathways were identified, and common targets between phytochemicals and pathways were sorted. A further network of phytochemicals-pathways-targets was constructed followed by molecular docking of highly enriched disease targets and phytochemicals. RESULTS: An in silico study revealed that 19 main active compounds of AC are interacting with 48 targets involved in regulating biological processes in the IHD. Molecular docking analyses were performed to explore the potential and affinity of these compounds with disease targets. Galangin, alpha-asarone, beta-asarone, and isoelemicin exhibited significant interactions with IHD disease targets, such as prostaglandin G/H synthase 2, cytochrome P450 1A2, transcription factor p65, vascular endothelial growth factor A, and tyrosine-protein kinase. Additionally, the study identified the interaction between the top 4 phytochemicals and the five most enriched disease targets. CONCLUSION: These findings provide a promising avenue for transforming bioactive phytoconstituents in AC into novel drug entities for treating IHD. The in silico approach identifies therapeutic targets, guides wet lab studies, and aids multi-compound management for IHD.