Abstract

NETWORK PHARMACOLOGY AND INTEGRATED MOLECULAR DOCKING REVEAL BIOACTIVE COMPONENTS AND POTENTIAL TARGETS OF TRIFOLIUM PRATENSE AGAINST PCOS.

Pralhad E. Mangale*, Rushikesh S. Sonawane, Rahul V. Takawale and Sahil F. Patel

Abstract

Aim: To study some phytoconstituents for the treatment of PCOS (polycystic ovarian syndrome) using Molecular docking, Network pharmacology, PPI, and Gene ontology approach. Objective: PCOS (Polycystic Ovary Syndrome) affects millions of women worldwide, causing hormonal imbalance and group of symptoms like hirsutism, obesity, irregular periods and infertility. There are limited drugs are available in market to overcome this symptom, and they have number of side effects. Herbal treatment is alternative way with potentially fewer side effects. So, we try to find new herbal treatment to overcome PCOS symptoms by using molecular docking, network pharmacology and analysis through PPI (Protein-Protein interaction) and GO (Gene Ontology) approach. These botanical remedies may help to regulate hormones, improve insulin sensitivity, and reduce inflammation, also give contribution to managing PCOS symptoms and try to improving overall quality of life. Material and Method We apply molecular docking criteria for screening the desired targets, this study was conducted on 2 different targets, which are estrogen and androgen protein, to find out the potential effect of 70 active phytoconstituents obtained from two plants such as Raktakanda and Pudina. From these criteria, we screened out 6 potential targets based on their affinities, who may be more effective against PCOS. Detailed information about these phytochemicals was gathered from the PubChem database, which provides valuable information regarding chemical structure and properties. To identify the potential targets and genes of respected phytoconstituents related to PCOS, we use bioinformatic tools such as Binding DB and Swiss Target Prediction databases. these tools helped in the detection of genes that are expressed on stimulation of targeted by the selected phytoconstituents. Furthermore, the Kegg Mapper database is used to find the gene ids and list of pathways through which these genes get expressed. In the next step, we collect the targets and genes related to PCOS by using the Gene Card database and screen out common targets between PCOS and phytoconstituents.to find more effective information also compared with hyperandrogenic and hypoestrogenic targets and genes. Further performed protein-protein interaction using the STRING database to identify strong interactions between targets, this information helps to find out potential synergistic effects. Then to understand the functional implication of the identified target genes, Gene Ontology functional enrichment analysis was conducted with the help of the Metascape database. Finally, to visualize the interaction between compounds, targets, genes, pathways, and disease we use cytoscape 3.10.1. Results: The result shows that out of 6 phytoconstituents, a pratensein is express more genes and the targets are associated with PCOS potentially they are P11511(aromatase), P03372(estrogen receptor), Q97731(estrogen receptor beta) with expression of genes has:1588(CYP19A), has:2099(ESR1), has:2100(estrogen receptor beta.

Keywords: P olycystic ovary syndrome (PCOS) Calycosin, Irilone, Pratensein, Pseudobaptigenin, molecular docking, network pharmacology.