Unraveling the oxidative stress inflammation nexus in metabolic syndrome and therapeutic opportunities

Abstract

Non-communicable diseases (NCDs) have overtaken infectious diseases as the leading cause of death in both industrialized and developing nations, following the successful control of many formerly widespread infections. Among these NCDs, metabolic syndrome (MetS)stands out as a significant global health threat. Characterized by a combination of metabolic disturbances including low levels of HDL-cholesterol, insulin resistance, hypercholesterolemia, hypertriglyceridemia, hypertension, and central obesity, MetS has become a major contributor to morbidity and mortality worldwide. Increasing evidence indicates that oxidative stress and low-grade chronic inflammation are central, interconnected processes that modulate the onset and progression of MetS. This review synthesizes current knowledge on the molecular drivers linking redox imbalance, inflammatory signaling, adipokine dysregulation, mitochondrial dysfunction, AGE–RAGE activation, and gut microbiota alterations to metabolic dysfunction. We also integrate emerging pathways including NLRP3 inflammasome activation, adipose tissue hypoxia, and mitochondrial quality-control mechanisms to provide an updated mechanistic framework. Furthermore, we examine therapeutic strategies targeting the oxidative–inflammatory axis, including antioxidants, anti-inflammatory agents, metabolic drugs (e.g., GLP-1 receptor agonists, SGLT2 inhibitors), nutraceuticals, microbiome-directed therapies, and novel interventions such as nanomedicine and gene-based approaches. By consolidating recent mechanistic, clinical, and translational evidence, this review highlights key molecular interactions, identifies research gaps, and outlines future directions for precision interventions aimed at reducing the burden of metabolic syndrome.