DECIPHERING THE THERAPEUTIC POTENTIAL OF MYRICA ESCULENTA IN ASTHAMA TREATMENT : AN IN DEPTH SYSTEMIC PHARMACOLOGY INVESTIGATION INTEGRATING MOLECULAR DOCKING, SIMULATION, UNSUPERVISED MACHINE LEARNING, AND GENE EXPRESSION ANALYSIS

Abstract

Asthma is increasingly prevalent worldwide, especially in developed nations. Traditional medicinal models have utilized plants, prompting many patients to seek alternative therapies due to the side effects of current asthma treatments. Ayurvedic and Indian texts document the medicinal use of plants, including Myrica esculenta (ME), which is rich in phytochemicals with significant medicinal potential. These compounds have shown promise in treating diabetes, ulcers, tumors, asthma, and stress. This study employed a comprehensive network pharmacology approach encompassing drug-likeness evaluation, target identification. By protein-protein interaction key constituents like Myricanol, Arjunolic acid, Gallic acid, Ellagic acid, Caffeic acid, Cyanidanol, and Quercetin were analyzed and therapeutic genes identified included IL6, STAT3, JUN, NFKB1, and RELA. Enrichment analysis revealed the pivotal roles of genes such as STAT3, IL6, JUN, NFKB1, and RELA in transcriptional machinery and cytokine production pathways, crucial in mediating allergic responses underlying asthma pathogenesis. Particularly, inhibition of STAT3 was identified as a potential strategy to suppress Th17 cell differentiation, thereby reducing allergic effects in asthma. Furthermore, disease pathway analyses unveiled a significant association between asthma symptoms and respiratory syncytial virus (RSV) bronchiolitis during infancy, shedding light on potential early-life origins of asthma. Importantly, ellagic acid emerged as a promising therapeutic agent for asthma, exhibiting high interaction and binding affinity with STAT3. Molecular docking, dynamics simulations, and chemical map spacing validated this finding, corroborating ellagic acid's potential as a targeted treatment for asthma. Expression analysis further confirmed the relevance of STAT3 in lung-related diseases, particularly asthma, underscoring its potential role as a therapeutic target in respiratory disorders. These collectively provide valuable insights into the molecular mechanisms underlying asthma pathogenesis and offer promising avenues for the development of novel therapeutic interventions targeting STAT3, and related pathways.