Computational Design of Herbal Inhibitors of PAI-1 for Accelerated Wound Healing

Background: Wounds are one of the significant health issues that can cause serious complications if left untreated. The proper management and treatment of wounds is highly essential to avoid the chances of developing infections and therefore promote timely healing. Plasminogen activator inhibitor-1 (PAI-1) is a potential therapeutic target that interrupts the activation of plasminogen in the wounded tissues required for the healing process and therefore delays the healing process. Plant-based therapeutics are always demanded for wound healing because of their potential efficacy, optimized pharmacokinetics, safety, and availability. Purpose: The aim of the current study is to identify potent plant-based molecules for wound healing and to understand the most probable underlying mechanisms of action for the same. Methods: Thus, a library was prepared consisting of eighty-five plant-based ligands derived from diverse plants such as aloe vera, turmeric, neem, ginseng, calendula, etc., which were traditionally used for the management of wounds and related issues. Results: Therefore, the prepared ligand library is computationally screened against a three-dimensional model of PAI1 to shortlist the potential leads, followed by molecular dynamic simulation to validate their thermodynamic stability. The resulting simulations of the PAI1-emodin complex over a 100 ns period revealed their high stability. Conclusion: Thus, emodin was proposed as a potential inhibitor of PAI1 and can be used to develop a newer wound healing agent.