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Deciphering the Mechanism of the Anti-Hypertensive Effect of Isorhynchophylline by Targeting Neurotransmitters Metabolism of Hypothalamus in Spontaneously Hypertensive Rats
journal contribution
posted on 2020-05-14, 14:34 authored by Yuan Li, Ruixue Yu, Dan Zhang, Wenqing Yang, Qingqing Hou, Yunlun Li, Haiqiang JiangEssential
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
the 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
in providing theoretical evidence for future research and clinical
application.