Hoang, S. H. | Search bioRxiv

bioRxiv2023

A Network Pharmacology Approach to Elucidate the Anti-inflammatory Effects of Ellagic Acid

Ellagic acid (EA) is a naturally occurring polyphenolic compound found in various fruits and vegetables like strawberries, raspberries, pomegranates, and nuts such as pecans and walnuts. With its antioxidant properties, EA has shown potential health benefits, although further research is necessary to fully comprehend its effects, mechanisms, and safe and effective application as a complementary medicine. Notably, there is accumulating evidence of EAs anti-inflammatory effects; however, the precise underlying mechanism remains unclear. To investigate the anti-inflammatory properties of EA, a network pharmacology approach was employed. The study identified 52 inflammation-related targets of EA and revealed significant signaling pathways and relevant diseases associated with inflammation through GO and KEGG analysis. Furthermore, topological analysis identified 10 important targets, including AKT1, VEGFA, TNF, MAPK3, ALB, SELP, MMP9, MMP2, PTGS2, and ICAM1. Molecular docking and molecular dynamics simulations (integrated with were conducted molecular mechanics Poisson-Boltzmann), indicating that AKT1, PTGS2, VEGFA, and MAPK3 are the most likely targets of EA. In summary, this study not only confirmed the anti-inflammatory effects of EA observed in previous research but also identified the most probable targets of EA.

pharmacology and toxicology↗

bioRxiv2022

Fibroblast Growth Factor 5 (FGF5) and Its Missense Mutant FGF5-Y174H Underlying Trichomegaly: A Molecular Dynamics Simulation Investigation

The missense mutation Y174H of FGF5 (FGF5-H174) had been associated with trichomegaly, characterized by abnormally long and pigmented eyelashes. The amino acid tyrosine (Tyr/Y) is conserved across many species, proposedly holding important characteristics for the functions of FGF5. One-microsecond molecular dynamics simulations along with protein-protein docking and residue interacting network analysis were employed to investigate the structural dynamics and binding mode of both wild-type (FGF5-WT) and its mutated counterpart (FGF5-Y174H). It was found that the mutation caused decreases in number of hydrogen bonds within the protein, sheet secondary structure, interaction of residues 174 with others, and number of salt-bridges. On the other hand, the mutation showed increases in solvent accessible surface area, number of hydrogen bonds between the protein and solvent, coil secondary structure, protein C-alpha backbone root mean square deviation, protein residue root mean square fluctuations, as well as occupied conformational space. In addition, protein-protein docking integrated with molecular dynamics simulations and molecular mechanics - Poisson-Boltzmann surface area (MM/PBSA) binding energy calculation demonstrated that the mutated variant possessed stronger binding affinity towards fibroblast growth factor receptor 1 (FGFR1). However, residue interaction network analysis demonstrated that the binding mode was drastically different from that of the FGF5-WT-FGFR1 complex. In conclusion, the missense mutation conferred more instability, stronger binding affinity towards FGFR1 but with distinctively altered binding mode or residue connectivity. These findings might help explain the decreased activation of FGFR1, underlying trichomegaly.

bioinformatics↗