Back to all available

Unveiling potential phytocompounds for Gastrointestinal Tract Disorders through integrative network pharmacology and molecular docking approaches

biochemistry
bioinformatics
computational-biology
gastroenterology-and-hepatology

Abstract

Abstract
Background. The global incidence of gastrointestinal tract (GIT) disorders is rising steadily, primarily attributed to shifts in dietary habits, sedentary lifestyles, and increased exposure to environmental stressors. Modern clinical medications offer immediate cures but can negatively affect the patient’s health, posing risks such as diabetes, cardiovascular issues, and damage to parts of the gastrointestinal system. History reveals the beneficial effects of herbal therapies, which utilize plants to treat various ailments with fewer side effects. The therapeutic effects of plants remain elusive; therefore, the current study aimed to identify potential phytochemicals and disease targets through network pharmacology, docking, and molecular dynamics simulations.
Methods. GIT-related targets were mined from databases and analyzed via Cytoscape and STRING to identify common nodes, followed by GO and KEGG enrichment analyses. Molecular docking and simulations were conducted to assess the potential of compounds targeting multiple disease-related proteins.
Results. An intersection analysis of disease-drug targets identified 65 targets corresponding to 121 active compounds, including core targets such as TP53, EGFR, CASP3, AKT, and IL6, which have higher degree values in the Cytoscape and PPI network. Docking analyses have identified the top ten active compounds: Withaferin, Hecogenin, Camptothecin, Friedelin, Epifriedelanol, Berberine, Gedunin, Solanidine, Cucurbitacins, and Terpine, based on their binding potential to targeted proteins. The Hecogenin exhibited the least binding energy with the EGFR (-9.9 kcal/mol), while Berberine showed a binding energy of -9.2 kcal/mol with CASP3. EGFR protein also displayed high binding affinities with Cucurbitacins (-9.6 kcal/mol) and Epifriedelanol (-9.4 kcal/mol). RMSD analysis showed that EGFR-Hecogenin exhibited ~3.0 Å for Cα atoms with an average ligand fit of ~6.0 Å, whereas CASP3-Berberine displayed ~1.3 Å for Cα and an average ligand fit of ~5.0 Å.
Conclusions. ADMET analysis also indicated better absorption, metabolism, and drug-likeness of these potential compounds, particularly Berberine and Hecogenin, which may lead to the development of drugs with minimal side effects for gastrointestinal therapies.
Ask to review this manuscript

Notes for potential reviewers

  • Volunteering is not a guarantee that you will be asked to review. There are many reasons: reviewers must be qualified, there should be no conflicts of interest, a minimum of two reviewers have already accepted an invitation, etc.
  • This is NOT OPEN peer review. The review is single-blind, and all recommendations are sent privately to the Academic Editor handling the manuscript. All reviews are published and reviewers can choose to sign their reviews.
  • What happens after volunteering? It may be a few days before you receive an invitation to review with further instructions. You will need to accept the invitation to then become an official referee for the manuscript. If you do not receive an invitation it is for one of many possible reasons as noted above.
  • PeerJ does not judge submissions based on subjective measures such as novelty, impact or degree of advance. Effectively, reviewers are asked to comment on whether or not the submission is scientifically and technically sound and therefore deserves to join the scientific literature. Our Peer Review criteria can be found on the "Editorial Criteria" page - reviewers are specifically asked to comment on 3 broad areas: "Basic Reporting", "Experimental Design" and "Validity of the Findings".
  • Reviewers are expected to comment in a timely, professional, and constructive manner.
  • Until the article is published, reviewers must regard all information relating to the submission as strictly confidential.
  • When submitting a review, reviewers are given the option to "sign" their review (i.e. to associate their name with their comments). Otherwise, all review comments remain anonymous.
  • All reviews of published articles are published. This includes manuscript files, peer review comments, author rebuttals and revised materials.
  • Each time a decision is made by the Academic Editor, each reviewer will receive a copy of the Decision Letter (which will include the comments of all reviewers).

If you have any questions about submitting your review, please email us at [email protected].