Multi-Omics Elucidation of Edulinine's Intervention Mechanism in Hypertensive Rats

Hypertension is a cardiovascular disorder characterized by sustained elevation of arterial blood pressure, in which vascular dysfunction serves as a key initiating factor leading to target organ injury. The indole alkaloid edulinine (Edu) represents a potential therapeutic agent for hypertension, although its specific mechanisms remain unclear. This study investigated the protective effects of Edu on vascular endothelial injury in N-⁠nitro-⁠L-⁠arginine-induced hypertensive rats using physiological, biochemical, and histopathological assessments. Through integrated proteomic and metabolomic analyses, we examined Edu's effects on thoracic aortic tissue proteins and serum metabolic profiles to elucidate its molecular mechanisms. The results demonstrated that Edu exhibited superior antihypertensive efficacy compared to sodium nitroprusside and effectively ameliorated hypertension-induced left ventricular systolic dysfunction. Furthermore, proteomic analysis indicated that compared with the Model group, Edu showed significant intersections in the tricarboxylic acid cycle, fatty acid degradation, oxidative phosphorylation, and fatty acid elongation pathways. These pathways are of great significance to lipid metabolism and energy metabolism and are closely related to fatty acid elongation and myocardial contraction. In the fatty acid degradation pathway, the proteins up-regulated by Edu almost exactly correspond to those down-regulated by the Control group. Metabolomics analysis revealed that Edu exerts its antihypertensive effects primarily by regulating biological pathways involved in bile acid metabolism, fatty acid metabolism, and lipid metabolism. The integrated analysis of metabolomics and proteomics demonstrated that Edu markedly reduced the abnormal up-regulation of OXSM and MECR in hypertensive rats, suggesting that Edu may systematically regulate the balance of the fatty acid metabolic network by regulating the carbon chain initiation and elongation processes in fatty acid synthesis, as well as the key reductive reactions in mitochondrial β-oxidation. In summary, the potential mechanism of the protective effect and antihypertensive effect of Edu on the thoracic aorta of L-NNA-induced hypertensive rats may be inhibiting the up-regulation of OXSM and MECR expression, regulating the dynamic balance of fatty acid degradation and synthesis, and improving fatty acid metabolism disorders. These findings indicate that Edu holds substantial research value as a potential therapeutic candidate for hypertension.