Bioactive Compounds and Signaling Pathways of Wolfiporia extensa in Suppressing Inflammatory Response by Network Pharmacology

Juri Jin; Md Helal Uddin Chowdhury; Md Hafizur Rahman; Ki-Young Choi; Md Adnan

doi:10.3390/life13040893

Bioactive Compounds and Signaling Pathways of Wolfiporia extensa in Suppressing Inflammatory Response by Network Pharmacology

Life (Basel). 2023 Mar 27;13(4):893. doi: 10.3390/life13040893.

Authors

Juri Jin¹, Md Helal Uddin Chowdhury², Md Hafizur Rahman³, Ki-Young Choi¹, Md Adnan³

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 Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.

Abstract

Wolfiporia extensa (WE) is a medicinal mushroom and an excellent source of naturally occurring anti-inflammatory substances. However, the particular bioactive compound(s) and mechanism(s) of action against inflammation have yet to be determined. Here, we studied anti-inflammatory bioactive compounds and their molecular mechanisms through network pharmacology. Methanol (ME) extract of WE (MEWE) was used for GC-MS analysis to identify the bioactives, which were screened by following Lipinski's rules. Public databases were used to extract selected bioactives and inflammation-related targets, and Venn diagrams exposed the common targets. Then, STRING and Cytoscape tools were used to construct protein-protein (PPI) network and mushroom-bioactives-target (M-C-T) networks. Gene Ontology and KEGG pathway analysis were performed by accessing the DAVID database and molecular docking was conducted to validate the findings. The chemical reactivity of key compounds and standard drugs was explored by the computational quantum mechanical modelling method (DFT study). Results from GC-MS revealed 27 bioactives, and all obeyed Lipinski's rules. The public databases uncovered 284 compound-related targets and 7283 inflammation targets. A Venn diagram pointed to 42 common targets which were manifested in the PPI and M-C-T networks. KEGG analysis pointed to the HIF-1 signaling pathway and, hence, the suggested strategy for preventing the onset of inflammatory response was inhibition of downstream NFKB, MAPK, mTOR, and PI3K-Akt signaling cascades. Molecular docking revealed the strongest binding affinity for "N-(3-chlorophenyl) naphthyl carboxamide" on five target proteins associated with the HIF-1 signaling pathway. Compared to the standard drug utilized in the DFT (Density Functional Theory) analysis, the proposed bioactive showed a good electron donor component and a reduced chemical hardness energy. Our research pinpoints the therapeutic efficiency of MEWE and this work suggests a key bioactive compound and its action mechanism against inflammation.

Keywords: HIF-1 signaling pathway; N-(3 chlorophenyl) naphthylcarboxamide; Wolfiporia extensa; inflammation; network pharmacology.

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.