Daidzein attenuates inflammation and pain via TRPV1/ERK/COX-2 pathway modulation: insights from computational and in vivo studies

Abstract

The animal and computational studies were conducted to elucidate the anti-inflammatory and analgesic potential of the Daidzein (isoflavone in nature). The molecular docking of the Daidzein was commenced against the inflammatory and analgesic targets i.e., COX-2 (Cyclooxygenase-2), ERK (Extracelluar receptor kinase), and TRPV1 (Transient receptor Potential Vanilloid 1) protein. The molecular docking was followed by the molecular dynamic (MD) simulation assess the dynamic stability of the complexes over time. Following MD simulation, the binding free energy calculations were conducted to determine the thermodynamic binding affinity. After the computational studies, the results were validated using the acetic acid-induced writhing and formalin-induced models. The molecular docking of the Daidzein showed multiple hydrophilic and hydrophobic interactions. The MD simulation analysis showed that the Daidzein_COX-2, Diadizein_ERK, and Daidzein_TRPV1 complex showed that complexes remains stable using RMSD (Root mean square deviation), RMSF (Root mean square fluctuations), RoG (Radius of Gyration), SASA (Solvent accessible surface area) and hydrogen bond analysis. The binding free energy calculations using MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) and MM-GBSA Molecular Mechanics Generalized-Born Surface Area) revealed favorable binding free energy and the total energy of the system remains negative. Furthermore, the Daidzein showed marked reduction in the writhing movement and increased the pain threshold. Similarly, the Daidzein also evidently reduced the Formalin-induced biphasic pain response in animals when the results were compared with the Disease control. In conclusion, the Daidzein portrayed promising anti-inflammatory and analgesic activities using computational and animal studies, however, additional studies will be required to employ it clinically.