Research progress and mechanistic exploration of Ophiopogon japonicus polysaccharides in the treatment of obesity-related diabetes and cardiovascular diseases: A narrative review.

Ophiopogon japonicus polysaccharides (OJPs), the principal bioactive constituents of a traditional medicine and food homologous herb, exhibit multi-target protective effects against obesity-related diabetes and cardiovascular comorbidities. This narrative review employs a conceptual mechanism-oriented framework-from structural signatures through gut microbial metabolites to host signaling pathways to disease phenotypes-to consolidate current knowledge on OJPs. Structurally, OJPs exhibit diverse glycosidic linkages, branching topologies, and chemical modifications (sulfation, carboxylation) that determine bioactivity. Mechanistically, OJPs ameliorate diabetes via InsR/IRS-1/PI3K/Akt/Glut-4 activation, SCFA-GPR41/43-GLP-1 secretion, and IKK/NF-κB-mediated β-cell protection, and confer cardiovascular protection through S1P/S1P1/Akt/ERK/eNOS angiogenesis, Nrf2/GPX4 anti-ferroptosis, and NF-κB/Cox-2 suppression, while restoring intestinal barrier integrity to reduce metabolic endotoxemia. Four cross-talk nodes-the NF-κB nexus, PI3K/Akt-AMPK-PPAR triangle, Nrf2-NF-κB counterbalance, and SCFA-GPCR-metabolic axis-are proposed to coordinate these pathways within a gut microbiota-centered conceptual model. Priority future directions include clinical trials in comorbid patients, quantitative SAR matrices, gut-targeted delivery systems, and systematic replication with pharmacologic controls to support OJPs' application in comorbidity therapy.