Integrative biochemical and computational analysis identifies LOX-1 and IL-6R as therapeutic targets in oxidative, inflammatory and lipid dysregulation of ischemic stroke

Abstract

Background and Objective: Ischemic stroke (IS) being one of the leading causes of mortality and morbidity globally is initiated by complex interactions among lipid peroxidation, oxidative stress and metabolic dysfunction. This study aimed to identify therapeutic targets for these pathological pathways is critical for improving diagnostic and treatment strategies.

Methodology: This case control study comprising 150 patients and 100 healthy controls was conducted at DHQ Hospital, Gujranwala from June 2022 to June 2023. Biochemical analyses quantified apolipoproteins, oxidized lipoproteins (oxLDL, oxHDL), sdLDL, antioxidant factors (SOD), inflammatory (IL-6) and metabolic markers (ferritin, LDH) using ELISA and spectrophotometric assays. Moreover, molecular docking and 100 ns molecular dynamics (MD) simulations conducted to evaluate inhibitory potential and structural stability of selected small molecule ligands targeting major lipid related (LOX-1) and inflammatory (IL-6R) receptors.

Results: The stroke patients demonstrated significantly elevated levels of biochemical markers and a marked reduction in SOD activity (p< 0.05). Regression modeling highlighted oxHDL, apoCIII, ferritin, and LDH as robust independent predictors of ischemic stroke. IL-6 displayed positive correlation with oxidized lipoproteins and apolipoproteins, supporting a link between inflammatory signaling and lipid abnormalities. Computational studies identified strong ligand receptor binding with docking energies ranging from −5.9 to −8.0 kcal/mol.

Conclusion: Overall, integrated biochemical and computational approach highlights inflammatory activation, oxidative lipid damage, and iron dysregulation as vital contributors to stroke. Key receptors involved in lipid oxidation and cytokine signaling emerge as promising dual therapeutic targets, and the identified ligands show potential as lead candidates for future drug development against ischemic stroke.