Chemico-biological interaction unraveled the potential mechanistic pathway of Ixeridium dentatum compounds against atopic dermatitis

Juri Jin; Md Helal Uddin Chowdhury; Tuhin Das; Sourav Biswas; Ke Wang; Md Hafizur Rahman; Ki Young Choi; Md Adnan

doi:10.1016/j.compbiolchem.2023.107933

Chemico-biological interaction unraveled the potential mechanistic pathway of Ixeridium dentatum compounds against atopic dermatitis

Comput Biol Chem. 2023 Oct:106:107933. doi: 10.1016/j.compbiolchem.2023.107933. Epub 2023 Jul 21.

Authors

Juri Jin¹, Md Helal Uddin Chowdhury², Tuhin Das³, Sourav Biswas⁴, Ke Wang⁵, Md Hafizur Rahman⁶, Ki Young Choi⁷, Md Adnan⁸

Affiliations

¹ Division of Future Agriculture Convergence, College of Agriculture and Life Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
² Ethnobotany and Pharmacognosy Lab, Department of Botany, University of Chittagong, Chattogram 4331, Bangladesh.
³ Department of Microbiology, University of Chittagong, Chattogram 4331, Bangladesh.
⁴ Department of Chemistry, Clemson University, SC 29634, USA.
⁵ Department of Molecular Pharmaceutics, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA.
⁶ Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
⁷ Division of Future Agriculture Convergence, College of Agriculture and Life Science, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: choiky@kangwon.ac.kr.
⁸ Department of Molecular Pharmaceutics, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA; Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: mdadnan1991.pharma@gmail.com.

PMID: 37536229
DOI: 10.1016/j.compbiolchem.2023.107933

Abstract

This study aims to investigate the potential therapeutic application of Ixeridium dentatum (ID) in treating atopic dermatitis (AD) through network pharmacology, molecular docking, and molecular dynamic simulation. We employed GC-MS techniques and identified 40 bioactive compounds present in the ID and determined their targets by accessing public databases. The convergence of compounds and dermatitis related targets led to the identification of 32 common genes. Among them, IL1B, PTGS2, IL6, IL2, and RELA, were found to be significant targets which were analyzed using Cytoscape network topology. The KEGG pathway evaluation revealed that these targets were significantly enriched in the C-type lectin receptor signaling pathway. The therapeutic efficacy of Stigmasta-5,22-dien-3-ol, Urea, n-Heptyl-, and 3-Epimoretenol was demonstrated in molecular docking assay, as evidenced by their presence in the core compounds of the compound-target network. Furthermore, these compounds exhibited significant kinetic stability and chemical reactivity in DFT quantum analysis when compared to their co-crystallized ligands and reference drug, indicating their potential as key targets for future research. Among the top three docking complexes, namely IL6-3-Epimoretenol, and IL2- Stigmasta-5,22-dien-3-ol, both demonstrated exceptional dynamic characteristics in molecular dynamics simulations at 100 ns. The feasibility of these compounds could be attributed to the prior traditional interrelationship between ID and AD. Overall, this research elucidates the interplay between AD-associated signaling pathways and target receptors with the bioactive ID. The proposal posits the utilization of antecedent compounds as a substitute for the customary pharmaceutical intervention that obstructs the discharge of cytokines, which incite dermal inflammation in the C-type lectin receptor signaling pathway of atopic dermatitis.

Keywords: Atopic dermatitis; DFT analysis; Ixeridium dentatum; Molecular docking; Molecular dynamic simulation; Network pharmacology.

MeSH terms

Dermatitis, Atopic* / drug therapy
Drugs, Chinese Herbal*
Humans
Interleukin-2
Interleukin-6
Lectins, C-Type
Molecular Docking Simulation

Substances

Interleukin-2
Interleukin-6
Lectins, C-Type
Drugs, Chinese Herbal