Protocatechuic acid and syringin improve cardiac damage and autonomic imbalance caused by dyslipidemia in mice.

Background: Dyslipidemia causes complex cardiac pathologies associated with inflammation, fibrosis, and autonomic dysregulation. The prevention of heart damage induced by dyslipidemia and the mechanisms of action of the phenolic compounds protocatechuic acid and syringin remain incompletely elucidated. Purpose: This study investigated the role and mechanism of co-administration of two natural phenols, protocatechuic acid and syringin, previously isolated from Method: To induce dyslipidemia in C57BL/6 mice, they were fed a high-fat diet for 4 weeks. Subsequently, while maintaining the high-fat diet, mice received daily administration of protocatechuic acid (50 mg/kg), syringin (50 mg/kg), a combination of both, or simvastatin (10 mg/kg) for 12 weeks. Subsequent evaluations include noninvasive electrocardiogram and heart rate variability assessment, Spearman correlation analysis, blood lipid and cytokine analysis, histopathological evaluation, immunohistochemistry, and Western blot. Result: Combination therapy with protocatechuic acid and syringin restored plasma lipid profiles, reduced plasma cytokines, and inhibited collagen accumulation and myocardial fibrosis in cardiac tissue. It also restored cardiac electrophysiological function and improved autonomic imbalance by alleviating sympathetic nervous system dominance. Mechanistically, it inhibited the TLR4/Myd88 inflammatory pathway and upregulated the Nrf2/HO-1 antioxidant pathway. Conclusion: This approach, which simultaneously targets fibrosis, inflammation, oxidative stress, and autonomic nervous system imbalance, demonstrates the potential for a multi-target therapeutic strategy against complex cardiac diseases caused by dyslipidemia.