Deciphering the role of Sarpagandha (Rauvolfia serpentina Benth. ex Kurz) bioactives in managing insomnia: Insights from network pharmacology and molecular docking analysis

Introduction: Insomnia is defined as a complaint of disrupted sleep, which presents as early awakenings, trouble falling asleep or staying asleep, or both. Insomnia is a serious health concern for adults due to its association with deteriorating general health. Treatment for sleep disturbances using Complementary and Alternative Medicine (CAM) has a long history of use. Many research studies indicate that CAM may be beneficial for improving sleep. Sarpagandha ( Rauvolfia serpentina Benth. ex Kurz) is a well-known herbal remedy with therapeutic uses in Ayurvedic medicine and shows great promise as a phytopharmaceutical source for treating insomnia. Aim: The aim of this study was to identify the active potential components of Sarpagandha and understand their mechanism of action in insomnia through network pharmacology and molecular docking. Materials and Methods: Data mining of Sarpagandha bioactives was done using IMPPAT 2.0 (Indian Medicinal Plants, Phytochemistry and Therapeutics 2.0) and Dr. Duke database. Then, phytochemical dataset was screened using SwissADME, and a final list of bioactive phytochemicals was listed. BindingDB was used to get the targets associated with phytochemicals. Insomnia-related target genes were obtained from DisGeNet and GeneCards database. Venny tool was used to get an overlapping target set. The obtained target set was queried into the GoShiny database, and top 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were availed. Compound-Target and Compound-Target-Pathway datasets were imported to Cytoscape, and network mapping was done. Then, the network of Sarpagandha underwent topological assessment, and core bioactives and targets were listed. Molecular docking analysis was carried out using PyRx. The docking pose was visualized in BIOVIA Discovery studio. Results: The network analysis of Sarpagandha revealed 23 active ingredients and 29 important targets for insomnia management. KEGG pathway enrichment analysis for common targets indicated that the core ingredients may influence the neuroactive ligand-receptor pathway, the serotonergic synapse, the calcium signaling pathway, and the CAMP signaling pathways. The validation of molecular docking showed that four of the Sarpagandha ’s key components could bind steadily to the core targets of insomnia, suggesting that it is a good candidate for treating insomnia. Conclusion: This study summarizes the basic mechanism of action for the components of Sarpagandha and the therapeutic target genes for insomnia, offering a preliminary understanding of mode of action in ameliorating insomnia.