A target fishing and systems biology-metabolomics approach to surmise the pharmacological potential of Secamone emetica (Retz.) R.Br. ex Sm.

Abstract

Secamone emetica (Retz.) R.Br. ex Sm., a wild, edible woody liana indigenous to peninsular India, is used by local inhabitants to address various ailments, including abscesses, headaches, joint pain, leucorrhoea, dental caries, and neurological and genital disorders. However, its phytochemical potential remains untapped, and the above claims lack scientific validity. The study aims to profile and annotate the phytochemical and pharmacological complexity of S. emetica using metabolomics, target fishing and network pharmacology approaches. Hydroalcoholic extracts of S. emetica plant parts were subjected to LC-ESI-MS analysis in positive and negative ionisation modes and statistically compared by multivariate analysis. Target fishing was performed using BindingDB, STITCH, and the Swiss TargetPrediction tools. The targets were mapped using DisGeNET, KEGG, and Reactome databases, and networks were drawn using Cytoscape 3.10.2. Gene ontology, functional enrichment, and in silico hub target validations were performed. The LC-ESI-MS identified 95 compounds in S. emetica, including emetine and cephaeline. MetaboAnalyst revealed significant differences in metabolomic profiles across plant parts. Target fishing predicted 430 gene targets, and topology studies revealed the top 31 core interactive targets (CITs). Untargeted disease and pathway network association with the 31 CITs identifies their roles in nervous system disorders and carcinogenesis-receptor activation. In silico validation on eFP showed tissue-specific differential expression of CITs, highlighting their potential expression in the nervous system. This study presents a comprehensive metabolomic profile of S. emetica, discovering its phytochemical intricacy and elucidating its potential biological functions. It reveals significant pharmacological mechanisms and surmises its interactions in the serotonergic synapse.