NETWORK PHARMACOLOGY APPROACH : BIOACTIVE PHYTOCHEMICALS FROM SALVIA OFFICINALIS L.TARGETING SRC FOR THE TREATMENT OF COLORECTAL CANCER

Abstract

Colorectal cancer (CRC) is one of the most common disease across the globe, around millions of cases are being diagnosed each year. Targeted therapy using bioactive compounds obtained from medicinal plants for various disease has gained a lot interest in the past decade. There is a rising need for identification for more safe and effective treatment strategies to reduce to mortality rate of cancer. Treatment using traditional medicinal herbs leads to less side effects as compared to conventional cancer therapies. Network pharmacology approach provides insights into pharmacological mechanisms of phytochemicals obtained from therapeutic herbs. This method utilizes various databases software for predicting the relationship between bioactive compound and target protein involved in pathogenesis of disease, then its affinity is determined by bioinformatics analysis such as Molecular docking simulations. Network pharmacology is a useful approach for discovery of novel drug candidates. Salvia officinalis L., also known as sage plant have shown to contain around 749 active phytochemicals in different parts according to IMPPAT and KNApSAcK databases. The OMIM (Online Mendelian Inheritance in Man) and Genecards databases provides information regarding gene targets involved in CRC. The venn plot between common target genes of phytochemicals and the disease target genes showed 12 common targets, that act as potential key players in promoting CRC carcinogenesis. These 12 common genes are modulated by phytochemicals of salvia officinalis L., these were subjected to KEGG (Kyoto Encyclopedia of Genes and Genomics) and GO (Gene Ontology) enrichment analysis, which predicts the involvement of target gene in specific pathway of disease. String database predicts the protein-protein interaction, explaining the relationship ranking between bioactive compound and the target genes. This network of drug-target pathway and PPI is visualized by using Cytoscape. Protein-Protein interactions provides information complex interaction network between these proteins in CRC. SRC gene which encodes for protein tyrosine kinase came out to be highest scoring gene in Cytoscape analysis. Lastly, Molecular docking simulations was performed to analyze the affinity of interaction between selected bioactive phytochemicals and its target gene. We obtained structure of Src kinase (2H8H) from RCSB protein databank. The results showed that bioactive phytochemicals (Hispidulin, 6-Epi-beta-bisabolol) present in Salvia officinalis L. can be potential inhibitor of Src kinase which is encoded by SRC gene. This comprehensive method demonstrates the effectiveness of medicinal plants in treatment of cancer and lays the groundwork for comprehending the efficaciousness of herbal remedies.

The use of medicinal plant is increasing worldwide, many FDA approved drugs are obtained from medicinal plants. Hence, the need for new potential bioactive compound that functions as potential drug is in demand in healthcare. The significance and relevance of these studies are underscored by the growing interest in complementary medicine. By combining science with traditional knowledge, new treatment options for cancer can be investigated, providing hope for safer and more effective treatments.