Deciphering the multi-scale mechanisms of Tephrosia purpurea against polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: Studies from network pharmacological perspective

•T. purpurea, a popular Ayurvedic herb of splenomegaly, is examined against PCOS.•Dataset of 76 phytochemicals (PCs) in T. purpurea is created via literature survey.•Targeting capabilities of 76 PCs against 542 human proteins are evaluated.•Regulatory prospects of 30 drug-like PCs (DPCs) against 161 PCOS-proteins.•Phytochemical, Rotenone having structural similarity with 30 DrugBank drugs.•8 DPCs against PCOS and its psychiatric comorbidities via targeting 6 proteins. Tephrosia purpurea (T. purpurea), a plant belonging to Fabaceae (pea) family, is a well-known Ayurvedic herb and commonly known as Sarapunkha in traditional Indian medicinal system. Described as “Sarwa wranvishapaka”, i.e. having a capability to heal all types of wounds, it is particularly recognized for its usage in splenomegaly. Towards exploring the comprehensive effects of T. purpurea against polycystic ovarian syndrome (PCOS) and three comorbid neuropsychiatric diseases (anxiety, depression, and bipolar disorder), its constituent phytochemicals (PCs) were extensively reviewed and their network pharmacology evaluation was carried out in this study. The complex regulatory potential of its 76 PCs against PCOS is enquired by developing and analyzing high confidence tripartite networks of protein targets of each phytochemical at both pathway and disease association scales. We also developed a high-confidence human Protein-Protein Interaction (PPI) sub-network specific to PCOS, explored its modular architecture, and probed 30 drug-like phytochemicals (DPCs) having multi-module regulatory potential. The phytochemicals showing good binding affinity towards their protein targets were also evaluated for similarity against currently available approved drugs present in DrugBank. Multi-targeting and synergistic capacities of 12 DPCs against 10 protein targets were identified and evaluated using molecular docking and interaction analyses. Eight DPCs as a potential source of PCOS and its comorbidity regulators are reported in T. purpurea. The results of network-pharmacology study highlight the therapeutic relevance of T. purpurea as PCOS-regulator and demonstrate the effectiveness of the approach in revealing action-mechanism of Ayurvedic herbs from holistic perspective.