Antihypertensive activity of different components of Veratrum alkaloids through metabonomic data analysis

Zhaoli Zhou; Juan Chen; Yuzi Cui; Rihong Zhao; Hao Wang; Rui Yu; Tiantian Jin; Jinggong Guo; Yue Cong

doi:10.1016/j.phymed.2023.155033

Antihypertensive activity of different components of Veratrum alkaloids through metabonomic data analysis

Phytomedicine. 2023 Nov:120:155033. doi: 10.1016/j.phymed.2023.155033. Epub 2023 Aug 16.

Authors

Zhaoli Zhou¹, Juan Chen², Yuzi Cui¹, Rihong Zhao¹, Hao Wang¹, Rui Yu¹, Tiantian Jin¹, Jinggong Guo³, Yue Cong⁴

Affiliations

¹ State key Laboratory of Antiviral Drugs, Engineering Center of Henan Province of Eucommia ulmoides Cultivation and Utilization, School of Pharmacy, Henan University, Kaifeng 475004, China.
² State key Laboratory of Antiviral Drugs, Engineering Center of Henan Province of Eucommia ulmoides Cultivation and Utilization, School of Pharmacy, Henan University, Kaifeng 475004, China; The First Medical Center of the Chinese People's Liberation Army General Hospital, Beijing 100141, China.
³ Center for Multi-Omics Research, National Key Laboratory of Cotton Bio-breeding and Integrated Utilization, School of Life Sciences, Henan University, Kaifeng 475004, China. Electronic address: jgguo@henu.edu.cn.
⁴ State key Laboratory of Antiviral Drugs, Engineering Center of Henan Province of Eucommia ulmoides Cultivation and Utilization, School of Pharmacy, Henan University, Kaifeng 475004, China. Electronic address: congyue@henu.edu.cn.

PMID: 37647672
DOI: 10.1016/j.phymed.2023.155033

Abstract

Background: Hypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 - 30% of hypertensive patients. Therefore, it is imperative to develop new treatments for hypertension. Veratrum alkaloids were once used for the clinical treatment of hypertension, the mechanism of which is still unclear. It was gradually phased out due to adverse reactions.

Purpose: This study aimed to investigate the short-term and long-term hypotensive profiles of different components of Veratrum alkaloids in spontaneously hypertensive rats (SHRs) to unveil their mechanisms of action.

Results: Total Veratrum alkaloid (V), component A (A), and veratramine (M) quickly decreased BP within 30 min of treatment, reduced renal and cardiovascular damage, and improved relevant biochemical indicators (nitric oxide [NO], endothelin-1 [ET-1], angiotensin II [Ang II)], noradrenaline [NE], etc) in SHRs to delay stroke occurrence. Thereinto, A exhibited excellent protective effects in cardiovascular disease. The metabolomic profiles of SHRs treated with V, A, and M were significantly different from those of SHRs treated with vehicle. Thirteen metabolites were identified as potential pharmacodynamic biomarkers. Through Kyoto Encyclopedia of Genes and Genomes analysis, V, A, and M-induced hypotension was mainly related to alterations in nicotinate and nicotinamide metabolism, GABAergic synapses, linoleic acid metabolism, ketone body synthesis and degradation, arginine and proline metabolism, and urea cycle, of which nicotinate and nicotinamide metabolism was the key metabolic pathway to relieve hypertension.

Conclusion: This work shows that A is an effective and promising antihypertensive agent for hypertension treatment to reduce BP and hypertensive target organ damage, which is mainly mediated through modulating nicotinate and nicotinamide metabolism, RAS, and NO-ET homeostasis.

Keywords: Component A; Hypertension; Metabonomics; Total Veratrum alkaloid; Veratramine; Veratrum nigrum L..

MeSH terms

Animals
Antihypertensive Agents / pharmacology
Data Analysis
Humans
Hypertension* / drug therapy
Niacin*
Niacinamide
Rats
Veratrum Alkaloids

Substances

Antihypertensive Agents
Niacin
Veratrum Alkaloids
Niacinamide