Vasorelaxant effect of monoterpene carvacrol on isolated human umbilical artery

Đukanović, Đorđe; Bojic, Milica Gajic; Marinković, Sonja T.; Trailovic, Sasa M.; Stojiljković, Miloš P.; Škrbić, Ranko

doi:10.1139/cjpp-2021-0736

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…Preparations obtained from umbilical cords serve as a tool for important research fields, such as models for in vitro study of cardiovascular diseases, including pre‐eclampsia (Medina Leyte et al., 2020 ). Moreover, in vitro searches for new substances with relaxant properties are based on the use of isolated umbilical arteries and veins (Đukanović et al., 2022 ). In addition to being an excellent model for testing the vasoactivity of substances, the advantage of the umbilical blood vessels is based primarily on their good availability and harmlessness for the patient, because the umbilical cord is treated as biological waste (Stefos et al., 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Methodological challenges in using human umbilical artery as a model for in vitro studies

Gajić Bojić,

Đukanović,

Marinković

et al. 2023

Experimental Physiology

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New Findings What is the central question of this study?What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding and its importance?The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries. AbstractHuman umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre‐eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L‐type voltage‐operated calcium channels and different types of potassium channels (KATP, BKCa and KV) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin‐induced contraction and a decrease in minoxidil‐induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that KATP and KV channels participate in the minoxidil‐induced relaxation, while L‐type voltage‐dependent Ca2+ channels play an important role in the serotonin‐induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine‐induced pre‐eclampsia model.

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Section: Introductionmentioning

confidence: 99%

Methodological challenges in using human umbilical artery as a model for in vitro studies

Gajić Bojić,

Đukanović,

Marinković

et al. 2023

Experimental Physiology

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Essential Oil-Derived Monoterpenes in Drug Discovery and Development

Ijinu,

Prabha,

Pushpangadan

et al. 2023

Drug Discovery and Design Using Natural Products

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Design of Novel TRPA1 Agonists Based on Structure of Natural Vasodilator Carvacrol—In Vitro and In Silico Studies

Đukanović,

Suručić,

Bojić

et al. 2024

Pharmaceutics

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Considering the escalating global prevalence and the huge therapeutic demand for the treatment of hypertension, there is a persistent need to identify novel target sites for vasodilator action. This study aimed to investigate the role of TRPA1 channels in carvacrol-induced vasodilation and to design novel compounds based on carvacrol structure with improved activities. In an isolated tissue bath experiment, it was shown that 1 µM of the selective TRPA1 antagonist A967079 significantly (p < 0.001) reduced vasodilation induced by 3 mM of carvacrol. A reliable 3D-QSAR model with good statistical parameters was created (R2 = 0.83; Q2 = 0.59 and Rpred2 = 0.84) using 29 TRPA1 agonists. Obtained results from this model were used for the design of novel TRPA1 activators, and to predict their activity against TRPA1. Predicted pEC50 activities of these molecules range between 4.996 to 5.235 compared to experimental pEC50 of 4.77 for carvacrol. Molecular docking studies showed that designed molecules interact with similar amino acid residues of the TRPA1 channel as carvacrol, with eight compounds showing lower binding energies. In conclusion, carvacrol-induced vasodilation is partly mediated by the activation of TRPA1 channels. Combining different in silico approaches pointed out that the molecule D27 (2-[2-(hydroxymethyl)-4-methylphenyl]acetamide) is the best candidate for further synthesis and experimental evaluation in in vitro conditions.

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Vasorelaxant effect of monoterpene carvacrol on isolated human umbilical artery

Cited by 3 publications

References 41 publications

Methodological challenges in using human umbilical artery as a model for in vitro studies

Methodological challenges in using human umbilical artery as a model for in vitro studies

Essential Oil-Derived Monoterpenes in Drug Discovery and Development

Design of Novel TRPA1 Agonists Based on Structure of Natural Vasodilator Carvacrol—In Vitro and In Silico Studies

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