Mechanisms of Action of<i>Uncaria rhynchophylla</i>Ethanolic Extract for Its Vasodilatory Effects

Loh, Yean Chun; Ch’ng, Yung Sing; Tan, Chu Shan; Ahmad, Mariam; Asmawi, Mohd Zaini; Yam, Mun Fei

doi:10.1089/jmf.2016.3804

Cited by 23 publications

(12 citation statements)

References 34 publications

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“…It has a strong inhibitory effect on the cardiovascular system and significantly reduces blood pressure; it has obvious nerve conduction block infiltration anesthesia and spinal canal anesthesia; it has a significant inhibitory effect on the synaptic transmission process of the central nervous system and has antiepileptic effects [5][6][7]. It can be used to treat hypertension, sedation, sleeping, and antispasmodic effects [8][9][10][11][12]. e indole alkaloids of Uncaria rhynchophylla are the main active ingredients.…”

Section: Introductionmentioning

confidence: 99%

Tissue Distribution of Hirsutine and Hirsuteine in Mice by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry

Zhou

Chen

2020

Journal of Analytical Methods in Chemistry

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Hirsutine and hirsuteine were two alkaloid monomers extracted from the traditional Chinese medicine Uncaria rhynchophylla, which have pharmacological effects such as antihypertension, anti-infection, and heart protection. An ultrahigh-performance liquid chromatography-mass spectrometry was established for the determination of hirsutine and hirsuteine in tissues (liver, kidney, heart, spleen, brain, and lung), and their absorption, distribution, and metabolism were studied for providing information on its pharmacological mechanism. UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) was used for chromatographic separation. The mobile phase was acetonitrile-0.1% formic acid, with a gradient elution, and the total run time was 4 min. Electrospray was used in the positive ion mode, and the multiple reaction monitoring (MRM) mode was for quantification. The acetonitrile precipitation method was used to remove protein-treated mouse plasma and tissue homogenate samples. In the concentration range of 2–5000 ng/g, hirsutine and hirsuteine in tissues showed good linearity (r > 0.995), and the lower limit of quantification was 2 ng/g. In the plasma and liver tissues, the interday and intraday precision of hirsutine and hirsuteine was less than 15%, the accuracy was between 90.9% and 110.1%, and the average recovery was better than 73.0%. The matrix effect was between 86.2% and 104.7%. The results showed that the precision, accuracy, recovery, and matrix effects meet the requirements for the study on the distribution of hirsutine and hirsuteine. After intraperitoneal administration of 10 mg/kg hirsutine and hirsuteine in mice, the distribution levels were highest in liver and kidney tissues, followed by the spleen and lung. Hirsutine and hirsuteine were low in brain tissue, but had obvious distribution, suggesting that they may pass through the blood-brain barrier.

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Section: Introductionmentioning

confidence: 99%

Tissue Distribution of Hirsutine and Hirsuteine in Mice by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry

Zhou

Chen

2020

Journal of Analytical Methods in Chemistry

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“…Furthermore, PGI 2 produced by COX in the vascular endothelium will bind to the IP receptor that located on the membrane of the adjacent VSMCs, and causes the activation of AC and up-regulation of cAMP; hence, this results in vasodilation. Therefore, NO/sGC/cGMP and COX are major pathways that should be investigated during the mechanisms of actions study on vasodilatory effects of test compounds [ 5 , 86 ].…”

Section: General Integration Of Vasodilative Receptorsmentioning

confidence: 99%

“…The increasing production of the Ca 2+ -calmodulin complexes in the vascular endothelium will activate both the eNOS and CSE to produce NO and H 2 S, respectively, and resulting in vasodilation. Therefore, both G s α-protein-coupled β 2 -adrenergic and G q α-protein-coupled M 3 receptors pathways are essential to be included in the mechanisms of actions study on vasodilatory effects of test compounds [ 5 , 90 , 91 ].…”

Section: General Integration Of Vasodilative Receptorsmentioning

confidence: 99%

“…The activation of IP 3 R is strictly dependent on the activation of G q α-protein-coupled receptors, which allows the Ca 2+ ions released from the store of sacroplasmic reticulum into the cytosol. Therefore, all these channel-linked pathways should be investigated during the mechanisms of actions study on vasodilatory effects of test compounds [ 5 , 86 , 87 , 88 , 89 , 90 , 91 ].…”

Section: General Integration Of Vasodilative Receptorsmentioning

confidence: 99%

“…However, before the vasculature-related research is carried out, the signaling mechanism pathways happening in the vasculature should be clearly understood. Previous reviews have shown that aortic ring assay is recommended as the “golden tool” in most of the in vitro pharmacological research, especially those related to vasculature, along with the protocols and suggested antagonists that are to be used for different mechanism studies [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Overview of the Microenvironment of Vasculature in Vascular Tone Regulation

Loh

Tan

Ch’ng

et al. 2018

IJMS

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Hypertension is asymptomatic and a well-known “silent killer”, which can cause various concomitant diseases in human population after years of adherence. Although there are varieties of synthetic antihypertensive drugs available in current market, their relatively low efficacies and major application in only single drug therapy, as well as the undesired chronic adverse effects associated, has drawn the attention of worldwide scientists. According to the trend of antihypertensive drug evolution, the antihypertensive drugs used as primary treatment often change from time-to-time with the purpose of achieving the targeted blood pressure range. One of the major concerns that need to be accounted for here is that the signaling mechanism pathways involved in the vasculature during the vascular tone regulation should be clearly understood during the pharmacological research of antihypertensive drugs, either in vitro or in vivo. There are plenty of articles that discussed the signaling mechanism pathways mediated in vascular tone in isolated fragments instead of a whole comprehensive image. Therefore, the present review aims to summarize previous published vasculature-related studies and provide an overall depiction of each pathway including endothelium-derived relaxing factors, G-protein-coupled, enzyme-linked, and channel-linked receptors that occurred in the microenvironment of vasculature with a full schematic diagram on the ways their signals interact. Furthermore, the crucial vasodilative receptors that should be included in the mechanisms of actions study on vasodilatory effects of test compounds were suggested in the present review as well.

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Preclinical pharmacokinetic studies of villocarine A, an active Uncaria alkaloid

Chiang,

Chear,

Berthold

et al. 2024

Drug Testing and Analysis

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Villocarine A is a bioactive indole alkaloid isolated from the Uncaria genus. It has demonstrated vasorelaxation activity and potential to protect the central nervous system. To identify the pharmacokinetic properties of villocarine A, a series of in vitro and in vivo studies have been performed. Villocarine A was found to be highly permeable (15.6 ± 1.6*10−6 cm/s) across human colorectal adenocarcinoma cell monolayer with high protein binding (>91%) in both rat and human plasma. Hepatic extraction ratio of villocarine A was 0.1 in pooled rat liver and 0.2 in human liver microsomes and was found stable in rat plasma at 37°C. Due to the high permeability and low rate of metabolism properties, villocarine A was initially considered suitable for preclinical development and an ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for quantification (linearity: 1–150 ng/ml) in rat plasma was developed and validated for in vivo studies. Essential pharmacokinetic parameters included the volume of distribution and clearance of villocarine A, which were found to be 100.3 ± 15.6 L/kg and 8.2 ± 1.1 L/h/kg, respectively, after intravenous administration in rats. Following oral dosing, villocarine A exhibited rapid absorption as the maximum plasma concentration (53.2 ± 10.4 ng/ml) occurred at 0.3 ± 0.1 h, post‐dose. The absolute oral bioavailability of villocarine A was 16.8 ± 0.1%. To our knowledge, this was the first pharmacokinetic study of villocarine A, which demonstrated the essential pharmacokinetic properties of villocarine A: large volume distribution, high clearance, and low oral bioavailability in rats.

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Mechanisms of Action ofUncaria rhynchophyllaEthanolic Extract for Its Vasodilatory Effects

Cited by 23 publications

References 34 publications

Tissue Distribution of Hirsutine and Hirsuteine in Mice by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry

Tissue Distribution of Hirsutine and Hirsuteine in Mice by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry

Overview of the Microenvironment of Vasculature in Vascular Tone Regulation

Preclinical pharmacokinetic studies of villocarine A, an active Uncaria alkaloid

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