Mechanism of vasorelaxation induced by eupatorin in the rats aortic ring

Yam, Mun Fei; Tan, Chu Shan; Ahmad, Mariam; Shibao, Ruan

doi:10.1016/j.ejphar.2016.06.047

Cited by 30 publications

(11 citation statements)

References 13 publications

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“…Our results are in accordance with previous studies which proved that methoxy-flavones, structurally related to compound 18 , elicit vasodilation [ 65 , 66 ], at least partly, through an endothelium-dependent mechanism that involves activation of the NO/cGMP pathway [ 65 ]. However, our findings differ from those of other researchers who found that certain methoxy-flavones produce an endothelium-dependent vasodilatory effect via activation of the potassium channels [ 67 , 68 ]. Apparently, differences in the type and position of the substituents on the basic flavone skeleton greatly influence the mechanism underlying the vasodilator effect of these compounds, as evidenced by the fact that 5,4′-dihydroxy-3,7,8,3′-tetramethoxyflavone produces an endothelium-independent vasorelaxation, mediated by potassium channels activation [ 69 ], whereas 3,5,7,3′,4′-pentamethoxyflavone induces a vasorelaxant effect, which provokes the release of NO and H 2 S, but surprisingly without activating potassium channels [ 70 , 71 ].…”

Section: Discussioncontrasting

confidence: 99%

Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine

et al. 2018

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Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC50), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC50, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4′-trihydroxy-3,7-dimethoxyflavone (EC50, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H2S/ATP-sensitive potassium channel (KATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4′-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4′-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.

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Section: Discussioncontrasting

confidence: 99%

Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine

et al. 2018

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“…The production of these second messengers are strictly dependent on the activation of various types of the receptors that are located on the vasculature including EDRFs, enzyme-linked, G-protein-coupled, and channel-linked receptors. According to literatures, the vasodilative receptors are more frequently being included in the experimental study on mechanisms of actions of test compounds rather than vasoconstrictive receptors [ 86 , 87 , 88 , 89 , 90 , 91 ]. Therefore, following the current trend of pharmacological research, all the vasodilation-mediated receptors pathways that should be investigated during the mechanisms of actions study of test compounds were suggested at this section.…”

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%

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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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“…Also, diabetes is correlated with the superabundant production of reactive oxygen species (ROS) by hyperglycemia, which contributes to the elimination of endothelium-derived relaxing factor nitric oxide (NO) and the accumulation of endogenous vasoconstrictor substances, such as endothelin-1 [ 5 , 6 ]. Both in vitro and in vivo evidence demonstrate that high glucose condition obstructs acetylcholine-mediated endothelium-dependent relaxation (EDR) and interdicts the generation of NO [ 7 ]. From this respect, the vasomotor function may also be implicated in hyperglycemia vascular remodeling.…”

Section: Introductionmentioning

confidence: 99%

Emblic Leafflower (Phyllanthus emblica L.) Fruits Ameliorate Vascular Smooth Muscle Cell Dysfunction in Hyperglycemia: An Underlying Mechanism Involved in Ellagitannin Metabolite Urolithin A

Zhou

Zhang

Zheng

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Ellagitannins in Phyllanthus emblica L. (emblic leafflower fruits) have been thought of as the beneficial constituents for ameliorating endocrinal and metabolic diseases including diabetes. However, the effect of emblic leafflower fruits on diabetic vascular complications involved in ellagitannin-derived urolithin metabolites is still rare. In this study, acetylcholine-induced endothelium-independent relaxation in aortas was facilitated upon emblic leafflower fruit consumption in the single dose streptozotocin-induced hyperglycemic rats. Emblic leafflower fruit consumption also suppressed the phosphorylation of Akt (Thr308) in the hyperglycemic aortas. More importantly, urolithin A (UroA) and its derived phase II metabolites were identified as the metabolites upon emblic leafflower fruit consumption by HPLC-ESI-Q-TOF-MS. Moreover, UroA reduced the protein expressions of phosphor-Akt (Thr308) and β-catenin in a high glucose-induced A7r5 vascular smooth muscle cell proliferation model. Furthermore, accumulation of β-catenin protein and activation of Wnt signaling in LiCl-triggered A7r5 cells were also ameliorated by UroA treatment. In conclusion, our data demonstrate that emblic leafflower fruit consumption facilitates the vascular function in hyperglycemic rats by regulating Akt/β-catenin signaling, and the effects are potentially mediated by the ellagitannin metabolite urolithin A.

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Mechanism of vasorelaxation induced by eupatorin in the rats aortic ring

Cited by 30 publications

References 13 publications

Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine

Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine

Overview of the Microenvironment of Vasculature in Vascular Tone Regulation

Emblic Leafflower (Phyllanthus emblica L.) Fruits Ameliorate Vascular Smooth Muscle Cell Dysfunction in Hyperglycemia: An Underlying Mechanism Involved in Ellagitannin Metabolite Urolithin A

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