Systems-Level Network Pharmacology analysis of Terminalia chebula (Haritaki): Deciphering Multi-Target Mechanisms Across Inflammation-Metabolism-Immunity Axis

Background

Chronic inflammatory disorders result from complex interactions among inflammation, metabolic dysregulation, and immune imbalance. Conventional single-target therapies often fail to address this complexity. Terminalia chebula (Haritaki), an important Ayurvedic medicinal plant, is traditionally used for inflammatory, metabolic, and immune-related disorders; however, its integrated molecular mechanisms remain insufficiently understood.

Objectives

This study aimed to elucidate the systems-level, multi-target mechanisms of Terminalia chebula across the inflammation-metabolism-immunity axis using network pharmacology and molecular docking approaches.

Materials and Methods

Bioactive compounds of T. chebula were screened from IMMPAT and Dr. Duke databases using ADME criteria. Potential targets were predicted using SwissTargetPrediction and BindingDB, while disease-related targets were obtained from GeneCards. Overlapping targets were analyzed through compound-target and protein-protein interaction networks, followed by hub gene identification and KEGG pathway enrichment. Molecular docking was performed to validate ligand-target interactions.

Results

Thirty-two bioactive compounds and 150 overlapping targets were identified. Key phytoconstituents included quercetin, ellagic acid, and fatty acids, while hub genes comprised TNF, BCL2, ESR1, MMP9, EGFR, SRC, and CASP3. Enriched pathways involved Rap1, PI3K-Akt, MAPK, and PPAR signaling. Molecular docking demonstrated favorable binding affinities (≤-4 kcal/mol), supporting stable ligand-protein interactions.

Conclusion

Terminalia chebula exerts therapeutic effects through coordinated multi-component, multi-target modulation of interconnected inflammatory, metabolic, and immune pathways, providing a scientific basis for its traditional use in complex chronic disorders.