Inhibitory Potential of Silychrystin on ERR‐γ, Keap‐1, and NF‐κB Proteins in Acute Pancreatitis Explored Through Molecular Docking and Molecular Dynamics Simulation

Abstract

Acute pancreatitis (AP) presents a substantial burden in India, characterized by evolving disease patterns and life‐threatening complications. Globally, the increasing incidence of AP underscores the urgent need for effective therapeutic interventions. Key proteins such as ERR‐γ, Keap‐1, and NF‐κB play pivotal roles in the pathophysiology of AP, contributing to dysregulated molecular pathways and cellular interactions. Targeting these proteins offers a promising avenue to modulate these dysregulated pathways and improve AP outcomes. Smilax perfoliata, widely recognized for its diverse medicinal properties, presents a promising opportunity for the exploration of novel antipancreatitis agents, although data on its efficacy remains limited. In this study, we employed molecular docking simulations to evaluate the binding interactions between 23 identified phytocompounds from Smilax perfoliata and the target proteins ERR‐γ, Keap‐1, and NF‐κB. Among the compounds tested, silychrystin exhibited the highest binding affinity with Keap‐1 (−11.2 kcal/mol), followed by ERR‐γ (−10.2 kcal/mol) and NF‐κB (−8.5 kcal/mol). Additionally, a 200‐ns molecular dynamics simulation using GROMACS (GROningen MAchine for Chemical Simulations) confirmed the stability of the silychrystin‐target protein complex, revealing consistent interaction stability and minimal structural fluctuations. These findings suggest that silychrystin could serve as a promising therapeutic candidate for AP, warranting further research to evaluate its efficacy in preclinical and clinical settings.