Embelin targets PI3K/AKT and MAPK in age-related ulcerative colitis: an integrated approach of microarray analysis, network pharmacology, molecular docking, and molecular dynamics

Abstract

Vaibhdang, an Ayurvedic treatment for Crohn’s and UC, has been used for centuries. The main component of Vaibhdang is embelin derived from Embelia ribes. However, the pharmacological and molecular mechanisms of embelin in UC remain unclear. This study investigated the molecular targets and mechanisms of action of embelin in UC using microarray analysis, network pharmacology, molecular docking, and molecular dynamics simulations. Embelin targets were obtained by Swiss Target, TargetNet, STITCH, ChEMBL, and TCMSP. Ulcerative colitis targets were mapped using DisGenNET, Genecards, TCMSP, Therapeutic targets, and GEO databases (GSE87466). Co-targets between ulcerative colitis and embelin were identified, and a PPI network was constructed using the STRING database. To identify the core targets, we used Cytoscape to analyze the topology of the PPI network. There were 545 effective Embelin targets and 5171 effective ulcerative colitis targets, including 1470 DEG targets. ShinyGo and AutoDock were used to analyze GO and KEGG enrichment pathways and docking studies, respectively. Venn diagram analysis revealed 327 core targets of embelin in UC. An enrichment study showed that embelin is involved in PI3K-AKT, MAPK, RAS, and chemokine signalling. The top ten core targets docked with embelin and AKT1, MAPK1, and SRC complexes were utilized as representations and simulated using GROMACS for 100 ns. A comparison of native proteins and their complex interactions with embelin revealed that embelin might act on various PI3K/AKT and MAPK targets to treat ulcerative colitis. This study provides insights into the molecular targets and mechanisms of action of embelin against ulcerative colitis.

Communicated by Ramaswamy H. Sarma

Keywords:

• Embelin
• Network pharmacology
• Molecular dynamics
• Molecular docking
• DEG’s
• PI3K/AKT
• MAPK pathway
• Ulcerative colitis

Acknowledgments

The authors thank the VIT management for providing the infrastructural facilities.

Authors’ contributions

PSJ conceptualized the study and performed the research. KT supervised the study and provided the guidance throughout the research process. Both authors revised the manuscript and contributed in conducting experiment.

Disclosure statement

The authors declare there is no competing financial interest or personal interest to influence the reported research work.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.