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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Research Article

Pharmacological Screening of Species from the Lippia genus, Content in Terpenes and Phenylpropanoids, and their Vasorelaxing Effects on Human Umbilical Artery

Author(s): Debora de Menezes Dantas, Luís Pereira-de-Morais, Andressa de Alencar Silva, Renata Evaristo Rodrigues da Silva, Francisco Junio Dias, Thais de Sousa Amorim, Natália Cruz-Martins, Henrique Douglas Melo Coutinho* and Roseli Barbosa

Volume 29, Issue 7, 2023

Published on: 13 December, 2022

Page: [535 - 542] Pages: 8

DOI: 10.2174/1381612829666221124101321

Price: $65

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Abstract

Background: Naturally occurring bioactive compounds have a plethora of biological effects.

Objective: In this study, we examined a pharmacological screening of natural products on the human umbilical artery (HUA).

Methods: HUA preparations were used to follow contractions by KCl (60 mM) and tested at different concentrations (1-5000 μg/mL and μM) of the Lippia alba (EOLa) and Lippia origanoides (EOLo) essential oils, terpenes (citral, limonene perilic alcohol) and phenylpropanoids (eugenol, methyl eugenol).

Results: The reduction corresponded to approximately 100%, except for limonene (80 ± 1.2%). When evaluating the concentration of the natural product that promotes 50% relaxation of the HUA contracted by KCL, EC50 values were: 424.3 μg/mL (EOLa); 468.7 ± 6.7 μg/mL (EOLo); 264.2 ± 8.2 μM (citral); 677.8 ± 5.4 μM (limonene); 186.3 ± 6.4 μM (peryl alcohol); 986.4 ± 7.9 μM (eugenol); and 279.1 ± 4.4 μM (methyl-eugenol). Perillyl alcohol had a lower EC50 (consequently it has a higher pharmacological potency).

Conclusion: The plant extracts have a promising vasorelaxing effect in HUAs, paving the way for future investigations: as applications in diseases related to these vessels, such as preeclampsia.

Keywords: Vasorrelaxant, smooth muscle, natural products, human umbilical artery, terpenes, phenylpropanoids, preeclampsia.

[1]
Lahlou M. The success of natural products in drug discovery. Pharmacol Pharm 2013; 4(3): 17-31.
[http://dx.doi.org/10.4236/pp.2013.43A003]
[2]
Steegers EAP, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010; 376(9741): 631-44.
[http://dx.doi.org/10.1016/S0140-6736(10)60279-6] [PMID: 20598363]
[3]
Changaee F, Janani F. Seasonal variation in the prevalence of preeclampsia. J Family Med Prim Care 2017; 6(4): 766-9.
[http://dx.doi.org/10.4103/jfmpc.jfmpc_132_17] [PMID: 29564260]
[4]
Committee SP. SMFM Statement: benefit of antihypertensive therapy for mild-to-moderate chronic hypertension during pregnancy remains uncertain. Am J Obstet Gynecol 2015; 213(1): 3-4.
[http://dx.doi.org/10.1016/j.ajog.2015.04.013] [PMID: 26004324]
[5]
Bakkali F, Averbeck S, Averbeck D, Idaomar M. Biological effects of essential oils: a review. Food Chem Toxicol 2008; 46(2): 446-75.
[http://dx.doi.org/10.1016/j.fct.2007.09.106] [PMID: 17996351]
[6]
Castro HG, Oliveira LO, Barbosa LCA, et al. Content and composition of the essential oil of five accessions of mint. Quim Nova 2004; 27(1): 55-7.
[http://dx.doi.org/10.1590/S0100-40422004000100011]
[7]
da Silva RER, de Morais LP, Silva AA, et al. Vasorelaxant effect of the Lippia alba essential oil and its major constituent, citral, on the contractility of isolated rat aorta. Biomed Pharmacother 2018; 108(August): 792-8.
[http://dx.doi.org/10.1016/j.biopha.2018.09.073] [PMID: 30253371]
[8]
Pereira-de-Morais L, Silva AA, da Silva RER, et al. Tocolytic activity of the Lippia alba essential oil and its major constituents, citral and limonene, on the isolated uterus of rats. Chem Biol Interact 2019; 297(297): 155-9.
[http://dx.doi.org/10.1016/j.cbi.2018.11.006] [PMID: 30447181]
[9]
Carvalho PMM, Macêdo CAF, Ribeiro TF, et al. Effect of the Lippia alba (Mill.) N.E. Brown essential oil and its main constituents, citral and limonene, on the tracheal smooth muscle of rats. Biotechnol Rep 2018; 17(17): 31-4.
[http://dx.doi.org/10.1016/j.btre.2017.12.002] [PMID: 29619330]
[10]
Cardoso-Teixeira A, Ferreira-da-Silva F, Peixoto-Neves D, et al. Hydroxyl group and vasorelaxant effects of perillyl alcohol, carveol, limonene on aorta smooth muscle of rats. Molecules 2018; 23(6): 1430.
[http://dx.doi.org/10.3390/molecules23061430] [PMID: 29899230]
[11]
Lahlou S, Figueiredo AF, Magalhães PJC, Leal-Cardoso JH, Gloria PD. Cardiovascular effects of methyleugenol, a natural constituent of many plant essential oils, in normotensive rats. Life Sci 2004; 74(19): 2401-12.
[http://dx.doi.org/10.1016/j.lfs.2003.09.063] [PMID: 14998717]
[12]
Peixoto-Neves D, Silva-Alves KS, Gomes MDM, et al. Vasorelaxant effects of the monoterpenic phenol isomers, carvacrol and thymol, on rat isolated aorta. Fundam Clin Pharmacol 2010; 24(3): 341-50.
[http://dx.doi.org/10.1111/j.1472-8206.2009.00768.x] [PMID: 19682086]
[13]
Fei JQ, Zhou HB, Shen YL, Chen XZ, Wang LL. A comparison study on the responses of umbilical arteries and thoracic aorts to the adrenergic receptor agonists. Cell Biol Int 2008; 32(3): S55-5.
[http://dx.doi.org/10.1016/j.cellbi.2008.01.234]
[14]
Velarde F, Castañeda V, Morales E, et al. Use of human umbilical cord and its byproducts in tissue regeneration. Front Bioeng Biotechnol 2020; 8(March): 117.
[http://dx.doi.org/10.3389/fbioe.2020.00117] [PMID: 32211387]
[15]
Medina-Leyte DJ, Domínguez-Pérez M, Mercado I, Villarreal-Molina MT, Jacobo-Albavera L. Use of human umbilical vein endothelial cells (HUVEC) as a model to study cardiovascular disease: A review. Appl Sci 2020; 10(3): 938.
[http://dx.doi.org/10.3390/app10030938]
[16]
Sousa DG, Sousa SDG, Silva RER, et al. Essential oil of Lippia alba and its main constituent citral block the excitability of rat sciatic nerves. Braz J Med Biol Res 2015; 48(8): 697-702.
[http://dx.doi.org/10.1590/1414-431x20154710] [PMID: 26132093]
[17]
Barbosa R, Cruz-Mendes Y, Silva-Alves KS, et al. Effects of Lippia sidoides essential oil, thymol, p-cymene, myrcene and caryophyllene on rat sciatic nerve excitability. Braz J Med Biol Res 2017; 50(12): e6351.
[http://dx.doi.org/10.1590/1414-431x20176351] [PMID: 29069226]
[18]
Pereira-de-morais L, Silva ADA, Evaristo R, Bastos MDS, Araújo IM, Henrique R, et al. Bronchodilator activity of the essential oil from Lippia sidoides in bronchial isolated from swine sus scrofa domesticus. An da Acad Cear Ciencias 2020; 4(1): 33-40.
[19]
Mildenberger E, Biesel B, Siegel G, Versmold HT. Nitric oxide and endothelin in oxygen-dependent regulation of vascular tone of human umbilical vein. Am J Physiol Heart Circ Physiol 2003; 285(4): H1730-7.
[http://dx.doi.org/10.1152/ajpheart.00938.2002] [PMID: 12969885]
[20]
Hiroaki N, Ryuji U, Kimiko K, Nozomi K, Tsuyako O, Kenji K. Mechanisms mediating the vasorelaxing action of eugenol, a pungent oil, on rabbit arterial tissue. Jpn J Pharmacol 1999; 79(3): 327-34.
[http://dx.doi.org/10.1254/jjp.79.327] [PMID: 10230861]
[21]
Criddle DN, Madeira SVF, de Moura RS. Endothelium-dependent and -independent vasodilator effects of eugenol in the rat mesenteric vascular bed. J Pharm Pharmacol 2010; 55(3): 359-65.
[http://dx.doi.org/10.1211/002235702694] [PMID: 12724042]
[22]
Peixoto-Neves D, Wang Q, Leal-Cardoso JH, Rossoni LV, Jaggar JH. Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels. Br J Pharmacol 2015; 172(14): 3484-94.
[http://dx.doi.org/10.1111/bph.13156] [PMID: 25832173]
[23]
Costa EE. Effect of eugenol on the contractile mechanism of the pulmonary artery in rats. Universidade Estadual do Ceará 2012.
[24]
Damiani CEN, Rossoni LV, Vassallo DV. Vasorelaxant effects of eugenol on rat thoracic aorta. Vascul Pharmacol 2003; 40(1): 59-66.
[http://dx.doi.org/10.1016/S1537-1891(02)00311-7] [PMID: 12646411]
[25]
Peixoto-Neves D, Leal-Cardoso JH, Jaggar JH. Eugenol dilates rat cerebral arteries by inhibiting smooth muscle cell voltage-dependent calcium channels. J Cardiovasc Pharmacol 2014; 64(5): 401-6.
[http://dx.doi.org/10.1097/FJC.0000000000000131] [PMID: 24921632]
[26]
Teófilo TM do NG. Antispasmodic effect of the essential oil of Lippia sidoides C ham and its constituents, thymol, paracymene and beta-caryophyllene, on the tracheal smooth muscle of rats. UNIVERSIDADE ESTADUAL DO CEARÁ 2012.
[27]
Quan A, Leung SWS, Lao TT, Man RYK. 5-hydroxytryptamine and thromboxane A2 as physiologic mediators of human umbilical artery closure. J Soc Gynecol Investig 2003; 10(8): 490-5.
[http://dx.doi.org/10.1016/S1071-5576(03)00149-7] [PMID: 14662162]
[28]
Santos-Silva AJ, Cairrão E, Verde I. Study of the mechanisms regulating human umbilical artery contractility. Health 2010; 2(4): 321-31.
[http://dx.doi.org/10.4236/health.2010.24049]
[29]
Lima CC, Criddle DN, Coelho-de-Souza AN, Monte FJQ, Jaffar M, Leal-Cardoso JH. Relaxant and antispasmodic actions of methyleugenol on guinea-pig isolated ileum. Planta Med 2000; 66(5): 408-11.
[http://dx.doi.org/10.1055/s-2000-8594] [PMID: 10909258]
[30]
Leal-Cardoso JH, Lahlou S, Coelho-de-Souza AN, et al. Inhibitory actions of eugenol on rat isolated ileum. Can J Physiol Pharmacol 2002; 80(9): 901-6.
[http://dx.doi.org/10.1139/y02-117] [PMID: 12430985]
[31]
Evaristo Rodrigues da Silva R, de Alencar Silva A, Pereira-de-Morais L, et al. Relaxant effect of monoterpene (-)-carveol on isolated human umbilical cord arteries and the involvement of ion channels. Molecules 2020; 25(11): 2681.
[http://dx.doi.org/10.3390/molecules25112681] [PMID: 32527034]
[32]
Campos J, Schmeda-Hirschmann G, Leiva E, et al. Lemon grass (Cymbopogon citratus (D.C) Stapf) polyphenols protect human umbilical vein endothelial cell (HUVECs) from oxidative damage induced by high glucose, hydrogen peroxide and oxidised low-density lipoprotein. Food Chem 2014; 151: 175-81.
[http://dx.doi.org/10.1016/j.foodchem.2013.11.018] [PMID: 24423518]
[33]
Speroni F, Rebolledo A, Salemme S, et al. Genistein effects on Ca2+ handling in human umbilical artery: inhibition of sarcoplasmic reticulum Ca2+ release and of voltage-operated Ca2+ channels. J Physiol Biochem 2009; 65(2): 113-24.
[http://dx.doi.org/10.1007/BF03179062] [PMID: 19886390]
[34]
Gunduz E, Arun O, Bagci ST, et al. Effects of propofol and sevoflurane on isolated human umbilical arteries pre-contracted with dopamine, adrenaline and noradrenaline. J Obstet Gynaecol Res 2015; 41(5): 697-703.
[http://dx.doi.org/10.1111/jog.12624] [PMID: 25511326]
[35]
Gupta S, Mehrotra S, Villalón CM, Perusquía M, Saxena PR, MaassenVanDenBrink A. Potential role of female sex hormones in the pathophysiology of migraine. Pharmacol Ther 2007; 113(2): 321-40.
[http://dx.doi.org/10.1016/j.pharmthera.2006.08.009] [PMID: 17069890]
[36]
Unlugenc H, Emre M, Demir C, Guler T, Kavak S, Isik G. Remifentanil-induced mechanical responses and membrane potential changes in human umbilical arteries. Acta Anaesthesiol Scand 2007; 51(2): 244-51.
[http://dx.doi.org/10.1111/j.1399-6576.2006.01210.x] [PMID: 17181535]
[37]
Hernandes C, Pina ES, Taleb-Contini SH, et al. Lippia origanoides essential oil: an efficient and safe alternative to preserve food, cosmetic and pharmaceutical products. J Appl Microbiol 2017; 122(4): 900-10.
[http://dx.doi.org/10.1111/jam.13398] [PMID: 28055127]
[38]
Kampke EH, de Souza Barroso ME, Marques FM, et al. Genotoxic effect of Lippia alba (Mill.) N. E. Brown essential oil on fish (Oreochromis niloticus) and mammal (Mus musculus). Environ Toxicol Pharmacol 2018; 59: 163-71.
[http://dx.doi.org/10.1016/j.etap.2018.03.016] [PMID: 29605588]
[39]
Api AM, Belsito D, Biserta S, Botelho D, Bruze M, Burton GA, et al. RIFM fragrance ingredient safety assessment, citral, CAS Registry Number 5392-40-5. Food Chem Toxicol 2019; 2020: 141.
[PMID: 32439587]
[40]
Gaworski CL, Vollmuth TA, York RG, Heck JD, Aranyi C. Developmental toxicity evaluation of inhaled citral in Sprague-Dawley rats. Food Chem Toxicol 1992; 30(4): 269-75.
[http://dx.doi.org/10.1016/0278-6915(92)90003-4] [PMID: 1628861]
[41]
Rodriguez AAM, Carvalho LJM, Kimura EA, Katzin AM. Perillyl alcohol exhibits in vitro inhibitory activity against Plasmodium falciparum and protects against experimental cerebral malaria. Int J Antimicrob Agents 2018; 51(3): 370-7.
[http://dx.doi.org/10.1016/j.ijantimicag.2017.08.025] [PMID: 28843818]
[42]
Kumar Joshi R, Soulimani R, Bouayed J. Limonene: Natural monoterpene volatile compounds of potential therapeutic interest. Am J Essent Oils Nat Prod 2019; 7(4): 1-10.
[43]
Sun J. D-Limonene: safety and clinical applications. Altern Med Rev 2007; 12(3): 259-64.
[PMID: 18072821]
[44]
Mohammadi Nejad S, Özgüneş H, Başaran N. Pharmacological and toxicological properties of eugenol. Turkish J Pharm Sci 2017; 14(2): 201-6.
[http://dx.doi.org/10.4274/tjps.62207]
[45]
National Toxicology Program. National Toxicology Program. Report on Carcinogens, Fourteenth Edition. Rep Carcinog 2016; 1948(Ntp 2000): p. 5. http://dataweb.usitc.gov/scripts/user_ set.asp%0Ahttp://ntp.niehs.nih.gov/go/roc14%0Ahttp://clinicaltrials.govclinicaltrials.gov/%0Ahttp://www.cdc.gov/noes/noes1/94220sic.html.%0Ahttp://toxnet.nlm.nih.gov/

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