Chinese Yam Polysaccharides Alleviate Myocardial Ischemia/Reperfusion Injury by Modulating Gut Microbiota, Restoring Mitochondrial Function, and Reducing Oxidative Stress

Background/Objectives: Myocardial ischemia/reperfusion (I/R) injury remains a critical challenge in cardiovascular disease management. Although Chinese yam polysaccharides (CYPs), the primary bioactive macromolecules isolated from Dioscorea opposita Thunb, exhibit well-documented antioxidant and anti-inflammatory properties, their cardioprotective efficacy against acute I/R injury and the underlying multiscale mechanisms remain unexplored. This study investigated the protective effects of CYPs using an in vivo mouse model of myocardial I/R injury. Methods: An in vivo mouse model of myocardial I/R injury was used to evaluate the effects of 7-day prophylactic CYPs treatment (400 mg/kg). Echocardiographic and histological analyses were performed, and serum myocardial injury biomarkers, oxidative stress indicators, pro-inflammatory cytokines, mitochondrial ultrastructure, ATP bioenergetics, mitochondrial respiratory chain gene expression, and gut microbiota composition were assessed. Results: Echocardiographic and histological analyses revealed that CYPs pretreatment significantly ameliorated cardiac dysfunction, as indicated by increased LVEF from 28.98% to 57.68% and reduced myocardial infarct size by 36.73% compared with the I/R group and decreased serum myocardial injury biomarkers, including CK-MB, LDH, and LDH-1. Mechanistically, CYPs exerted robust cardioprotection by mitigating oxidative damage, with MDA levels reduced by 28.83% and SOD activity increased to 1.76-fold that of the I/R group, and suppressing the release of pro-inflammatory cytokines, including Tnf-α, Il-6, and Il-1β. Crucially, CYPs intervention preserved mitochondrial ultrastructure and ATP bioenergetics, and levels increased to 1.51-fold that of the I/R group and upregulated the expression of essential mitochondrial respiratory chain genes, including mt-Nd1, mt-Nd4l, mt-Cyb, mt-CoII, and mt-Atp6. Furthermore, 16S rRNA sequencing showed that CYPs treatment reshaped gut microbiota and elevated the relative abundance of anti-inflammatory and antioxidant beneficial genus Akkermansia. Conclusions: Collectively, these findings provide novel evidence that CYPs confer profound protection against myocardial I/R injury through a multitargeted network involving the restoration of mitochondrial homeostasis, attenuation of oxidative inflammation, and modulation of the gut microbiome, highlighting CYPs as a promising functional food-derived candidate for adjunctive therapy in ischemic heart disease.