Integrated bimolecular network pharmacology approach on Andrographis paniculata and Cardiospermum halicacabum synergistic therapeutic effects in targeting breast cancer

Medicinal plants are a rich source of bioactive compounds, combination therapy of two plants treatment is gaining more prominence because of synergistic therapeutic effects. But, characterizing the molecular synergism activity of two medicinal herbal sources against specific drug targets in cancer is still considered a painstaking task that requires more meticulous screening, human intervention and high experimental resources. To understand the rationale, an integrated network pharmacology approach was introduced to understand the interaction network between compounds and drug targets. The interaction was constructed for compounds possessing >50% drug-likeness, non-mutagen non-carcinogen. Also, these compounds were compared in the activity landscape in a database of collective molecular activities of useful plants, only compounds <100µm were considered for bimolecular interaction with human drug target proteins. Further, a Venn diagram was constructed between genes of breast cancer and the gene that are mapped with Andrographis paniculata and Cardiospermum halicacabum. The STRING database was used to construct a protein-protein interaction network and relationships of each gene were analyzed. Consequently, GO biological function analysis and KEGG enrichment analysis for crucial targets were performed. Finally, docking of phytochemicals with drug target protein was carried out and its active site pharmacophore was reported. Thus, active ingredients owning pharmacophores of phenols and flavonoids exhibiting strong molecular interaction can be served as drug candidates for treating breast cancer. Moreover, herbal-based compounds potentially have fewer side effects and are safe for treatment.