Abstract

IN SILICO NETWORK PHARMACOLOGY INVESTIGATION OF TYPHONIUM TRILOBATUM IN PROTEIN-ENERGY MALNUTRITION: DECIPHERING BIOACTIVE COMPOUNDS, MOLECULAR TARGETS AND SIGNALING PATHWAYS

Dr. Ayush Kapoor*, Dr. Suman Panwar, Dr. Ekta Saini, Dr. Akshita Rana, Dr. Shivpriya

Abstract

Background: Protein Energy Malnutrition is a major global nutritional disorder characterized by impaired growth, metabolic dysfunction, immune suppression, oxidative stress, and progressive tissue wasting. Traditional ethnobotanical medicinal plants possessing nourishing and restorative properties may offer multitarget therapeutic potential in the management of PEM. Typhonium diversifolium has long been utilized in folklore medicine for its claimed nutritional and strengthening effects however, limited phytochemical documentation restricts systematic pharmacological investigation. Therefore, Typhonium trilobatum, a closely related species with better phytochemical representation, was selected for exploratory scientific validation of these traditional claims using a network pharmacology approach. Aim: The present study aimed to investigate the molecular mechanisms underlying the ethnobotanical nutritional claims associated with Typhonium trilobatum against Protein Energy Malnutrition through integrative network pharmacology analysis. Materials and Methods: Phytochemicals associated with Typhonium trilobatum were retrieved from the IMPPAT 2.0 Database and screened using SwissADME and MolSoft for pharmacokinetic evaluation and drug-likeness. Compound targets were predicted using SwissTargetPrediction, while disease-associated genes related to Protein Energy Malnutrition were retrieved from GeneCards and OMIM databases. Common targets were identified through Venn diagram analysis, followed by network construction using Cytoscape and hub gene analysis using the CytoHubba Plugin. Pathway enrichment analysis was performed using DAVID Bioinformatics Resources 2021. Results: A total of 9 phytochemicals were retrieved, among which 3 phytoconstituents satisfied the drug-likeness and ADME screening criteria. Target prediction yielded 278 targets, of which 241 unique targets remained after duplicate removal. Disease gene retrieval identified 248 PEM-associated genes, and comparative analysis revealed 15 overlapping targets. Network analysis highlighted the multitarget therapeutic nature of the selected phytochemicals, particularly thiamine, beta-sitosterol, and nicotinic acid. Hub gene analysis identified NOS2, TNF, CXCR3, MDM2, HCAR2, CA1, CA2, and F2 as significant regulatory targets. Pathway enrichment analysis revealed 41 enriched pathways, among which 20 pathways were directly linked to Protein Energy Malnutrition, including PI3K-Akt signaling, mTOR signaling, insulin resistance, HIF-1 signaling, adipocytokine signaling, and endocrine regulatory pathways. Conclusion: The present study provides preliminary scientific evidence supporting the traditional nutritional claims associated with Typhonium trilobatum in the management of Protein Energy Malnutrition. The identified phytoconstituents demonstrated multitarget interactions with inflammatory, metabolic, and nutritional regulatory pathways, suggesting promising therapeutic potential. The study also highlights the importance of scientifically validating extrapharmacopoeial (Anukta Dravya) medicinal plants through modern network pharmacology approaches.

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