Muhammad Haziq A Hamid, Ebru Toksoy Öner, Muhammad Hakimin Shafie
Obesity, diabetes, and hypertension are closely interconnected metabolic disorders that significantly increase the risk of cardiovascular complications and early mortality. Increasing attention has been directed toward natural polysaccharides as potential therapeutic agents due to their multifunctional biological activities and low toxicity. They regulate metabolic homeostasis through multiple pathways, including inhibition of adipogenesis and pancreatic lipase, modulation of carbohydrate-hydrolyzing enzymes, activation of insulin signalling pathways, regulation of the renin-angiotensin system, and improvement of gut microbiota composition and oxidative stress responses. This review summarizes recent advances in the anti-obesity, anti-diabetic, and antihypertensive activities of natural polysaccharides, focusing on their underlying mechanisms and structure-activity relationships. Importantly, this review provides a comparative synthesis of shared and disease-specific mechanisms across these three metabolic disorders while linking these activities to key structural features such as glycosidic linkages, molecular weight, monosaccharide composition and triple-helix formation. By integrating mechanistic insights with structural characteristics, this work highlights the potential of polysaccharides as multi-target agents for metabolic syndrome.