Deciphering the mechanism of the anti-hypertensive effect of isorhynchophylline by targeting neurotransmitters metabolism of hypothalamus in spontaneously hypertensive rats.

Essential hypertension is a major risk factor for cardiovascular disease that can lead eventually to structural and functional alterations in the brain. Accumulating evidence has suggested that the increased activities in renin-angiotensin system and sympathetic nerve participated in the pathogenesis of hypertension that is related to the imbalance between neurotransmitters. The potential role in essential hypertension arising from alterations of neurotransmitters in the central nervous system remains understudied. Isorhynchophylline is a major oxindole alkaloid extracted from Uncaria rhynchophylla, which has been widely used for treating hypertension and neurodegenerative diseases. Whether isorhynchophylline acts on neurotransmitters to lower blood pressure has been hypothesized but rarely demonstrated unequivocally. Here we studied the metabolic neurotransmitter profiles in the hypothalamus using a targeted metabolomic approach in spontaneously hypertensive rats after isorhynchophylline intervention. Our study demonstrated that isorhynchophylline exhibited a strong anti-hypertensive effect in spontaneously hypertensive rats by improving the neurotransmitter imbalance in the hypothalamus and inhibiting the overactivation of renin-angiotensin system and sympathetic nerve system. Overall, this study played an essential role in enhancing our understanding of the mechanism of isorhynchophylline in essential hypertension and providing theoretical evidence for future research and clinical application.