Deciphering the Mechanism of the Anti-Hypertensive Effect of Isorhynchophylline by Targeting Neurotransmitters Metabolism of Hypothalamus in Spontaneously Hypertensive Rats

Abstract

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 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.

Dissecting the potential mechanism of antihypertensive effects of RVPSL on spontaneously hypertensive rats via widely targeted kidney metabolomics

“…Tyrosine metabolism plays an important part in the pathological process of hypertension 19 . Tyrosine can be involved in the synthesis of catecholamine 20 …”

“…Tyrosine metabolism and thyroid hormone signaling pathway Tyrosine metabolism plays an important part in the pathological process of hypertension. 19 Tyrosine can be involved in the synthesis of catecholamine. 20 Under stress conditions, tyrosine can cause damage to the cell function and impair the vascular endothelium.…”

Therapeutic value of the metabolomic active neurotransmitter isorhynchophylline in the treatment of spontaneously hypertensive rats by regulating neurotransmitters

“…An earlier study by Li et al indicated the association of the antihypertensive effect of isorhynchophylline with tyrosine and glutamate metabolism in the hypothalamus, whereas in the present study we see isorhynchophylline treatment reduced blood pressure in SHRs through tyrosine and glutamate metabolism pathways in the hippocampus. Therefore, we can conclude that there are similar pathways from both brain regions involved in the antihypertensive effect of isorhynchophylline [ 18 ]; however, further work is required to ensure which part of the brain dominates the tyrosine and glutamate metabolism in association with the antihypertensive effect of isorhynchophylline. To conclude, the study outcomes reveal that tyrosine and glutamate metabolism is the main pathways, hindered by the intervention of isorhynchophylline, in the hippocampus region of the SHR group.…”

Unified Strategy Enables the Collective Syntheses of Structurally Diverse Indole Alkaloids

“…Unlike the aforementioned spirocyclic oxindole alkaloids, spirophyllines A–D ( 9 – 12 ) feature congested hexacyclic frameworks that include a rare isoxazolidine moiety and six to seven stereogenic centers, rendering them attractive but unexplored synthetic targets. Notably, several of these alkaloids display a wide range of biological effects, such as antidepressant (isorhynchophylline), anti-Alzheimer’s (rhynchophylline), anticancer (strychnofoline), , antihypertensive (isorhynchophylline), antiarrhythmia (spirophylline C), and anti-Parkinson’s disease (isorhynchophylline) . Owing to their promising bioactivities and intriguing structures, various spirocyclic oxindole alkaloids have challenged synthetic chemists…”