Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,is a persistent inflammatory disorder of the gastrointestinal system.Failures in existing therapy have generated interest in alternati...Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,is a persistent inflammatory disorder of the gastrointestinal system.Failures in existing therapy have generated interest in alternative treatments.This research examined the therapeutic efficacy of Dashamoola(DSM),an Ayurvedic polyherbal formulation,utilizing network pharmacology,molecular docking,microarray analysis,density functional theory(DFT),and molecular dynamics(MD)simulations.Bioactive compounds from DSM were obtained from the Indian Medicinal Plants,Phytochemistry and Therapeutics(IMPPAT)database,whereas IBD-related targets were found through the GeneCards and National Center for Biotechnology Information(NCBI)databases.Microarray datasets(GSE87466 for ulcerative colitis and GSE3365 for Crohn’s disease)were examined using Integrative Meta-Analysis of Gene Expression Omnibus(ImaGEO)to identify differentially expressed genes(DEGs)and perform a meta-analysis,uncovering significant targets.Protein-protein interaction(PPI)networks generated using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)and examined in Cytoscape revealed hub genes,such as tumor necrosis factor(TNF),interleukin-1 beta(IL1B),signal transducer and activator of transcription 3(STAT3),nuclear factor kappa B1(NFKB1),and C-C motif chemokine ligand 2(CCL2).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed the involvement of inflammatory pathways,gut barrier repair,and immunological regulation.Molecular docking studies revealed skimmin(-5.323 kcal/mol),hispidulin(-5.555 kcal/mol),umbelliferone(-5.052 kcal/mol),and pterocarpan(-5.091 kcal/mol)as significant bioactive compounds with strong binding affinities to IBD targets.MD simulations over 100 ns confirmed the stability and dynamics of these protein-ligand complexes.The investigation using DFT revealed the electronic stability and reactivity of these compounds,emphasizing skimmin and hispidulin for their ideal equilibrium of reactivity and stability.This integrated approach highlights the multi-target therapeutic potential of DSM in the treatment of IBD.The results provide a basis for further experimental confirmation and indicate DSM as a potential natural treatment for IBD management.展开更多
文摘Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,is a persistent inflammatory disorder of the gastrointestinal system.Failures in existing therapy have generated interest in alternative treatments.This research examined the therapeutic efficacy of Dashamoola(DSM),an Ayurvedic polyherbal formulation,utilizing network pharmacology,molecular docking,microarray analysis,density functional theory(DFT),and molecular dynamics(MD)simulations.Bioactive compounds from DSM were obtained from the Indian Medicinal Plants,Phytochemistry and Therapeutics(IMPPAT)database,whereas IBD-related targets were found through the GeneCards and National Center for Biotechnology Information(NCBI)databases.Microarray datasets(GSE87466 for ulcerative colitis and GSE3365 for Crohn’s disease)were examined using Integrative Meta-Analysis of Gene Expression Omnibus(ImaGEO)to identify differentially expressed genes(DEGs)and perform a meta-analysis,uncovering significant targets.Protein-protein interaction(PPI)networks generated using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)and examined in Cytoscape revealed hub genes,such as tumor necrosis factor(TNF),interleukin-1 beta(IL1B),signal transducer and activator of transcription 3(STAT3),nuclear factor kappa B1(NFKB1),and C-C motif chemokine ligand 2(CCL2).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed the involvement of inflammatory pathways,gut barrier repair,and immunological regulation.Molecular docking studies revealed skimmin(-5.323 kcal/mol),hispidulin(-5.555 kcal/mol),umbelliferone(-5.052 kcal/mol),and pterocarpan(-5.091 kcal/mol)as significant bioactive compounds with strong binding affinities to IBD targets.MD simulations over 100 ns confirmed the stability and dynamics of these protein-ligand complexes.The investigation using DFT revealed the electronic stability and reactivity of these compounds,emphasizing skimmin and hispidulin for their ideal equilibrium of reactivity and stability.This integrated approach highlights the multi-target therapeutic potential of DSM in the treatment of IBD.The results provide a basis for further experimental confirmation and indicate DSM as a potential natural treatment for IBD management.
