In silico Evaluation of Anti-inflammatory Compounds from Euphorbia hirta against Inflammatory Drug Target Proteins Associated with Asthma

Abstract

Background: Asthma is a chronic respiratory disease that affects the airways in the lungs. The airways become inflamed and narrow, making it difficult to breathe. Asthma symptoms can vary from person to person and can range from mild to severe. Aims: This study identified and evaluated potential anti-inflammatory compounds in Euphorbia hirta and assessed their ability to inhibit inflammatory drug targets associated with asthma using molecular docking analyses. Methodology: A comprehensive ligand library was constructed based on GC-MS analysis data of Euphorbia hirta, providing molecular details of various phytochemical compounds. Molecular docking simulations using AutoDock Vina, AutoDock tools, and Discovery Studio Visualizer were performed against target proteins associated with asthma (Interleukin 4, Interleukin 5, Leukotriene receptor, and Tumour Necrosis Factor-Alpha) to assess binding affinity and specificity of the compounds. Results: In the current study, Ergost-5-En-3-Ol, which is a sterol, was observed to be a promising lead compound for the development of anti-inflammatory drugs, as seen in the binding affinity. Ergost-5-En-3-Ol, a sterol compound, emerged as a promising lead candidate for potential anti-inflammatory drug development. It demonstrated significant binding affinity to the selected drug target proteins, particularly TNF-α, IL-4, IL-5, and Leukotrienes. The binding interactions involved in the active sites of these proteins indicated potential interference with inflammatory signalling, crucial for asthma pathology. Moreover, Ergost-5-En-3-Ol adheres to Lipinski's rule of five, suggesting potential oral bioavailability. Conclusion: This study confirms the anti-inflammatory properties of Euphorbia hirta and suggests its use for the development of a new therapeutic agent for managing asthma. Ergost-5-En-3-Ol warrants further investigation as a potential anti-inflammatory drug candidate. Furthermore, Ergost-5-En-3-Ol meets Lipinski's rule of five criteria, suggesting its potential for oral bioavailability, a crucial factor for drug development.