Harnessing Natural Products and Multi Omics to Modulate the Redox–Inflammation–Metabolism Axis in Brain Disorders: Insights from Computational and Experimental Models

Abstract

Abstract The intricate interplay between oxidative stress, neuroinflammation, and metabolic dysregulation underlies the pathogenesis of diverse brain disorders, including stroke, Alzheimer’s disease (AD), epilepsy, and traumatic brain injury (TBI). Emerging evidence highlights natural products as promising multitarget modulators of this redox–inflammation–metabolism axis. This review synthesises findings from preclinical studies, computational models, and multi‑omics analyses to elucidate how compounds such as mangiferin, curcumin, rhynchophylline, and herbal formulas exert neuroprotective effects through regulation of lipid metabolism, inflammasome signalling, and cell death pathways including ferroptosis and pyroptosis. Additionally, we discuss the contributions of computational biomechanics and seizure dynamics modelling, as well as gut microbiota metabolite interactions, to a systems‑level understanding of brain pathology. By integrating these diverse lines of evidence, we propose novel therapeutic strategies and highlight future directions for translating natural product‑based interventions into clinical practice. Keywords: Natural products; neuroinflammation; ferroptosis; gut–brain axis; multi‑omics; computational modelling; translational roadmap