Elucidating the molecular targets of Curcuma longa for breast cancer treatment using network pharmacology,molecular docking and molecular dynamics simulation

Background:To elucidate the molecular mechanisms of Curcuma longa(C.longa)in breast cancer treatment.Methods:Phytocompounds of C.longa were obtained from Dr.Duke’s Phytochemical and Ethnobotanical Database.Potential active targets were retrieved from Bindingdb,SEA and Swiss Target Prediction databases.Breast cancer targets were retrieved from the Therapeutic Target Database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were done using DAVID and KOBAS3.0 databases respectively.The Cytoscape software was used to construct the phytocompound-target-pathway network.The PyRx and Desmond software were utilized for molecular docking and molecular dynamics simulation respectively.Results:Out of one hundred and fifty-six phytocompounds,fifty-four modulated proteins involved in breast cancer.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated C.longa exerts its therapeutic effect through regulating several key pathways.Molecular docking analysis revealed that most phytocompounds of C.longa had a good affinity with the key targets.Molecular dynamics simulation showed that ethinylestradiol formed stable ligand-protein complexes.Conclusion:The results of this study will enhance our understanding of the potential molecular mechanisms by which C.longa inhibits breast cancer and lay a foundation for future experimental studies.

Antiplasmodial mechanism of Lawsonia inermis: An in silico based investigation

Background:Lawsonia inermis has been widely reported to be used as an herbal treatment for Malaria.However,despite several experimental studies about its antimalarial activities,the approach through which the herbal plant suppresses plasmodium infection is yet to be found.Consequently,this study uses computational approaches to understand the biological targets and pathways involved in the antiplasmodial activities of Lawsonia inermis compounds.Methods:The Gas Chromatography-Mass Spectrometry technique identified the phytocompounds present in the herbal plant.GeneCards,OMIM,and NCBI databases were explored to collate target proteins for further network pharmacology analysis.The phytocompounds were subjected to Absorption,Distribution,Metabolism,Excretion and Toxicity(ADMET)and druglikeness analysis.The STRING algorithm and Cytoscape were employed to develop and analyze the relationships among target proteins and compounds/targets/pathways network of the putative targets of the phytocompounds.Further computational analysis was carried out to identify potential drug leads.Results:Based on the Network Pharmacology studies,phytocompounds in Lawsonia inermis exhibit antiplasmodial activity by interacting with therapeutic genes that play essential roles in metabolism and signaling pathways.Notable among the genes are MMP9,MAPK1,HMOX1 and IDO1.Meanwhile,the most influenced pathways include the metabolic pathway,PI3K-Akt signaling pathway,and HIF-1 signaling pathway.ADMET analysis,molecular docking analysis,and molecular dynamics simulation revealed that 3-phenyl-2-Isoxazoline and 2-Dimethylamino-3’-methoxyacetophenone are recommendable drug leads for Malaria treatment as they form stable and favorable complexes with Matrix metalloproteinase-9(MMP9)target.Conclusion:The 3-phenyl-2-Isoxazoline and 2-Dimethylamino-3’-methoxyacetophenone phytocompounds from Lawsonia inermis herbal plant are predicted as antimalarial drug candidates and recommended for further wet-lab studies.