European Journal of Biomedical and Pharmaceutical Sciences

DECIPHERING THE ANTIHYPERGLYCEMIC MECHANISM OF PHALTRIKADI KWATHA IN PRAMEHA (T2DM): A NETWORK PHARMACOLOGY OF PHYTOCONSTITUENTS AND MOLECULAR TARGETS

Priyanka Sharma*, P. K. Prajapati, Sunil K. Dubey

ABSTRACT

Background: Type 2 Diabetes Mellitus (T2DM), correlated with Madhumeha (Kaphaja Prameha) in Ayurvedic medicine, represents a complex, systemic metabolic disorder driven by peripheral insulin resistance, progressive pancreatic $\beta$-cell dysfunction, chronic low-grade inflammation, and hepatic glucose overproduction. Phaltrikadi Kwatha (also known as Phalatrikadi Kashaya) is a traditional polyherbal decoction documented in Classical texts such as the Charaka Samhita. Although clinically valued for its therapeutic efficacy in metabolic disorders, its comprehensive modern molecular mechanism requires systematic characterization. Aim: This review aims to systematically map the active phytochemical landscape of Phaltrikadi Kwatha and elucidate its multi-component, multi-target, and multi-pathway antihyperglycemic network using an integrated computational and network pharmacology approach. Methods: Bioactive phytoconstituents across all candidate herbal ingredients of Phaltrikadi Kwatha were identified via database searching (TCMSP, IMPPAT, PubChem) and filtered using absorption, distribution, metabolism, and excretion (ADME) criteria (Oral Bioavailability $\ge 30\%$, Drug-likeness $\ge 0.18$). Associated molecular targets were retrieved using target-prediction platforms (SwissTargetPrediction, PharmMapper) and intersected with human T2DM target genes compiled from GeneCards, OMIM, and DisGeNET. Protein-Protein Interaction (PPI) networks were mapped using STRING and Cytoscape, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results: High-throughput computational screening highlighted key bioactive compounds including berberine, curcumin, gallic acid, ellagic acid, chebulagic acid, and $\alpha$-cyperone. These constituents converged upon major hub targets including AKT1, PPARG, TNF, IL6, MAPK1, MAPK3, and DPP4. Topological and functional pathway enrichment demonstrated that Phaltrikadi Kwatha primarily regulates the PI3K-Akt signaling pathway, AMPK signaling network, TNF/NF-$\kappa$B inflammatory cascade, and AGE-RAGE signaling axis in diabetic vascular tissues. Conclusion: Phaltrikadi Kwatha exerts its potent antihyperglycemic, insulin-sensitizing, antioxidant, and tissue-protective effects through a synergistic multi-target network. This holistic mechanism validates its historical usage in Prameha and offers clear molecular insights for modern therapeutic translational studies.

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