Skip to content
2000
Volume 25, Issue 2
  • ISSN: 1871-529X
  • E-ISSN: 2212-4063

Abstract

Background

La Llave (Rutaceae), commonly known as “zapote blanco”, is a tree widely distributed in Mexico's tropical and subtropical areas. The decoction of its leaves is traditionally used as a natural remedy to treat hypertension and anxiety.

Objectives

The present study aimed to determine the vasorelaxant and antihypertensive effects of extracts and evaluate the acute and sub-acute toxicity of one of the most active extracts.

Methods

The hydro-alcohol and organic (hexane, dichloromethane, and methanol) extracts, obtained from the leaves of , were evaluated on isolated aorta rat rings in the presence and absence of endothelium to determine their vasorelaxant effect. Then, most active extracts were studied to evaluate the functional mechanism of their vasorelaxant action and antihypertensive effect on spontaneously hypertensive rats (SHR). The acute and sub-acute toxicity of dichloromethane extract was evaluated following the OECD 423 and 407 protocols.

Results

The hexane (HE) and dichloromethane (DE) extracts from induced significant vasorelaxant action on isolated rat aortic rings with (Emax 104.7 ± 1.4% and Emax 97.3 ± 6.7%, respectively) and without (Emax 94.9 ± 3.5% and Emax 67.4 ± 1.0%, respectively) endothelium, and this effect was partially endothelium-dependent. Their vasorelaxant action was modified by L-NAME (nitric oxide synthase inhibitor) and ODQ (soluble guanylyl cyclase inhibitor); however, indomethacin did not modify the effect. Also, both HE and DE significantly decreased the contraction induced by KCl in a concentration-dependent manner and the maximal effect induced by CaCl. Moreover, DE showed a significant decrease in systolic and diastolic blood pressure in SHR at 7 hours and 15 days after treatment, respectively. Finally, the toxicity test of DE allowed classifying it in category 5, indicating it to be a non-toxic extract based on OECD guideline 423; the LD value was estimated to be greater than 2,000 mg/Kg and smaller than 5,000 mg/Kg in Wistar rats.

Conclusion

The results demonstrated hexane and dichloromethane extracts to exert a vasorelaxant effect through endothelium-dependent NO release and cGMP increase, as well as by calcium channel blockade. Also, dichloromethane extract showed efficacy and security as a potential antihypertensive agent.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/chddt/10.2174/011871529X346240250211090920
2025-02-17
2025-09-17

  • From This Site

    /content/journals/chddt/10.2174/011871529X346240250211090920
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Al GhoraniH. GötzingerF. BöhmM. MahfoudF. Arterial hypertension – Clinical trials update 2021.Nutr. Metab. Cardiovasc. Dis.2022321213110.1016/j.numecd.2021.09.007 34690044
     [Google Scholar]
  2. ForouzanfarM.H. LiuP. RothG.A. NgM. BiryukovS. MarczakL. AlexanderL. EstepK. Hassen AbateK. AkinyemijuT.F. AliR. Alvis-GuzmanN. AzzopardiP. BanerjeeA. BärnighausenT. BasuA. BekeleT. BennettD.A. BiadgilignS. Catalá-LópezF. FeiginV.L. FernandesJ.C. FischerF. GebruA.A. GonaP. GuptaR. HankeyG.J. JonasJ.B. JuddS.E. KhangY.H. KhosraviA. KimY.J. KimokotiR.W. KokuboY. KolteD. LopezA. LotufoP.A. MalekzadehR. MelakuY.A. MensahG.A. MisganawA. MokdadA.H. MoranA.E. NawazH. NealB. NgalesoniF.N. OhkuboT. PourmalekF. RafayA. RaiR.K. Rojas-RuedaD. SampsonU.K. SantosI.S. SawhneyM. SchutteA.E. SepanlouS.G. ShifaG.T. ShiueI. TedlaB.A. ThriftA.G. TonelliM. TruelsenT. TsilimparisN. UkwajaK.N. UthmanO.A. VasankariT. VenketasubramanianN. VlassovV.V. VosT. WestermanR. YanL.L. YanoY. YonemotoN. ZakiM.E.S. MurrayC.J.L. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990-2015.JAMA2017317216518210.1001/jama.2016.19043 28097354
     [Google Scholar]
  3. QiaoW. ZhangX. KanB. VuongA.M. XueS. ZhangY. LiB. ZhaoQ. GuoD. ShenX. YangS. Hypertension, BMI, and cardiovascular and cerebrovascular diseases.Open Med.202116114915510.1515/med‑2021‑0014 33585690
     [Google Scholar]
  4. Al-MakkiA. DiPetteD. WheltonP.K. MuradM.H. MustafaR.A. AcharyaS. BeheiryH.M. ChampagneB. ConnellK. CooneyM.T. EzeigweN. GazianoT.A. GidioA. Lopez-JaramilloP. KhanU.I. KumarapeliV. MoranA.E. SilwimbaM.M. RaynerB. SukonthasanA. YuJ. SaraffzadeganN. ReddyK.S. KhanT. Hypertension pharmacological treatment in adults: A world health organization guideline executive summary.Hypertension202279129330110.1161/HYPERTENSIONAHA.121.18192 34775787
     [Google Scholar]
  5. De FeoM. Del PintoR. PagliacciS. GrassiD. FerriC. Real-world hypertension prevalence, awareness, treatment, and control in adult diabetic individuals: An Italian nationwide epidemiological survey.High Blood Press. Cardiovasc. Prev.202128330130710.1007/s40292‑021‑00449‑7 33835433
     [Google Scholar]
  6. AgustinJ.A. SotoM. FamianiF. Cruz-CastilloJ.G. In situ, characterization of fruits and seeds of a number of white sapote (Casimiroa edulis Llave & Lex.) accessions in Mexico.HortScience201752121849185210.21273/HORTSCI12432‑17
     [Google Scholar]
  7. IbrahimN. El HawaryS. MohammedM. AliS. KandilZ. RefaatE. Chemical compositions and hypoglycemic activities of the protein and mucilage of Casimiroa edulis (Llave & Lex) seeds and fruits.J. Appl. Pharm. Sci.2019910849110.7324/JAPS.2019.91011
     [Google Scholar]
  8. YangD. QiuQ. XuL. XuY. WangY. The complete chloroplast genome sequence of Casimiroa edulis.Mitochondrial DNA B Resour.2019423979398010.1080/23802359.2019.1688711 33366279
     [Google Scholar]
  9. Barrera-CatalánE. Herrera-CastroN.D. Catalán-HeverásticoC. Ávila-SánchezP. Medicinal plants of the municipality of Tixtla de Guerrero, Mexico.Rev. Fitotec. Mex.201538110911110.35196/rfm.2015.1.109
     [Google Scholar]
  10. Lozoya-LegorretaX. Rodríguez-ReynagaD. Ortega-GalvánJ. Enriquez-HabibR. Isolation of a hypotensive substance from seeds of Casimiroa edulis.Arch. Invest. Med.197894565573 727850
     [Google Scholar]
  11. MagosG. VidrioH. Pharmacology of Casimiroa edulis; Part I. Blood pressure and heart rate effects in the anesthetized rat.Planta Med.1991571202410.1055/s‑2006‑960008 2062952
     [Google Scholar]
  12. Randolph MajorF.D. NotesN. N-dimethylhistamine, hypotensive principle in Casimiroa edulis Llave et Lex.J. Org. Chem.1958231564156510.1021/jo01104a612
     [Google Scholar]
  13. SarrisJ. McIntyreE. CamfieldD.A. Plant-based medicines for anxiety disorders, Part 1: A review of preclinical studies.CNS Drugs201327320721910.1007/s40263‑013‑0044‑3 23436255
     [Google Scholar]
  14. SatheeshN. Review on distribution, nutritional and medicinal values of Casimiroa edulis Llave – An underutilized fruit in Ethiopia.Am.-Eurasian J. Agric. Environ. Sci.20151515741583
     [Google Scholar]
  15. VidrioH. MagosG. Pharmacology of Casimiroa edulis; II. Cardiovascular effects in the anesthesized dog.Planta Med.199157321722010.1055/s‑2006‑960077 1896518
     [Google Scholar]
  16. KhaleelA.E.M. 2-phenyl-4-quinolinone alkaloids from Casimiroa edulis Llave & Lex (Rutaceae).Monatsh. Chem.2002133218318710.1007/s706‑002‑8248‑4
     [Google Scholar]
  17. AlyH.F. ElrigalN.S. AliA.S. RizkM.Z. EbrahimN.A. Modulatory effects of Casimiroa edulis on aluminium nanoparticles- associated neurotoxicity in a rat model of induced Alzheimer’s disease.J. Mater. Environ. Sci.2018919311941
     [Google Scholar]
  18. CanoL. Medicinal flora of Veracruz.Ethnobotanical Inventory.MexicoVeracruz University1997
     [Google Scholar]
  19. MagosG.A. VidrioH. EnríquezR. Pharmacology of Casimiroa edulis; III. Relaxant and contractile effects in rat aortic rings.J. Ethnopharmacol.19954711810.1016/0378‑8741(95)01247‑B 7564417
     [Google Scholar]
  20. Molina-HernándezM. Tellez-AlcántaraN.P. Pérez GarcíaJ. LopezJ.I.O. JaramilloM.T. Anxiolytic-like actions of leaves of Casimiroa edulis (Rutaceae) in male Wistar rats.J. Ethnopharmacol.2004931939810.1016/j.jep.2004.03.039 15182911
     [Google Scholar]
  21. Moo-HuchinV.M. Estrada-MotaI. Estrada-LeónR. Cuevas-GloryL. Ortiz-VázquezE. VargasM.L.V. Betancur-AnconaD. Sauri-DuchE. Determination of some physicochemical characteristics, bioactive compounds and antioxidant activity of tropical fruits from Yucatan, Mexico.Food Chem.201415250851510.1016/j.foodchem.2013.12.013 24444968
     [Google Scholar]
  22. RuízA.N. RamírezB.E.B. EstradaJ.G. LópezP.G. GarzónP. Anticonvulsant activity of Casimiroa edulis in comparison to phenytoin and phenobarbital.J. Ethnopharmacol.199545319920610.1016/0378‑8741(94)01216‑M 7623484
     [Google Scholar]
  23. Garzón-De la MoraP. García-LópezP.M. García-EstradaJ. Navarro-RuízA. Villanueva-MichelT. Villarreal-de PugaL.M. Casillas-OchoaJ. Casimiroa edulis seed extracts show anticonvulsive properties in rats.J. Ethnopharmacol.1999681-327528210.1016/S0378‑8741(99)00125‑7 10624888
     [Google Scholar]
  24. MagosG.A. VidrioH. ReynoldsW.F. EnríquezR.G. Pharmacology of Casimiroa edulis IV. Hypotensive effects of compounds isolated from methanolic extracts in rats and guinea pigs.J. Ethnopharmacol.1998641354410.1016/S0378‑8741(98)00101‑9 10075120
     [Google Scholar]
  25. BaischA.L.M. UrbanH. RuizA.N. Endothelium-dependent vasorelaxing activity of aqueous extracts of lyophilized seeds of Casimiroa edulis (AECe) on rat mesenteric arterial bed.J. Ethnopharmacol.2004952-316316710.1016/j.jep.2004.06.018 15507330
     [Google Scholar]
  26. BertinR. ChenZ. Martínez-VázquezM. García-ArgaézA. FroldiG. Vasodilation and radical-scavenging activity of imperatorin and selected coumarinic and flavonoid compounds from genus Casimiroa.Phytomedicine201421558659410.1016/j.phymed.2013.10.030 24309287
     [Google Scholar]
  27. FroldiG. BertinR. SecchiE. ZagottoG. Martinez-VazquezM. Garcia-ArgaezA. Vasorelaxation by extracts of Casimiroa spp. in rat resistancevessels resistancevessels and pharmacological study of cellular mechanisms.J. Ethnopharmacol.201113463764310.1016/j.jep.2011.01.008 21236328
     [Google Scholar]
  28. García GonzálezM. Freer BustamanteE. Morales MatamorosO. Acciones de Casimiroa edulis (Rutacea) sobre la presión arterial media y frecuencia cardiaca en ratas albinas.Rev. Biol. Trop.1994421-2115119 7480935
     [Google Scholar]
  29. Sánchez-RecillasA. Mantecón-ReyesP. Castillo-EspañaP. Villalobos-MolinaR. Ibarra-BarajasM. Estrada-SotoS. Tracheal relaxation of five medicinal plants used in Mexico for the treatment of several diseases.Asian Pac. J. Trop. Med.20147317918310.1016/S1995‑7645(14)60017‑1 24507636
     [Google Scholar]
  30. Arias-DuránL. Estrada-SotoS. Hernández-MoralesM. Millán-PachecoC. Navarrete-VázquezG. Villalobos-MolinaR. Ibarra-BarajasM. Almanza-PérezJ.C. Antihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: In vivo, functional ex vivo and in silico studies.J. Ethnopharmacol.202127311394810.1016/j.jep.2021.113948 33610712
     [Google Scholar]
  31. RussellJ.C. ProctorS.D. Small animal models of cardiovascular disease: Tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis.Cardiovasc. Pathol.200615631833010.1016/j.carpath.2006.09.001 17113010
     [Google Scholar]
  32. Hernández-AbreuO. Torres-PiedraM. García-JiménezS. Ibarra-BarajasM. Villalobos-MolinaR. MontesS. RembaoD. Estrada-SotoS. Dose-dependent antihypertensive determination and toxicological studies of tilianin isolated from Agastache mexicana.J. Ethnopharmacol.2013146118719110.1016/j.jep.2012.12.029 23276782
     [Google Scholar]
  33. OCDE_423. Test No. 423: Acute Oral Toxicity - Acute Toxic Class Method.Paris, FranceOECD2001
     [Google Scholar]
  34. Ávila-VillarrealG. González-TrujanoM.E. Carballo-VillalobosA.I. Aguilar-GuadarramaB. García-JiménezS. Giles-RivasD.E. Castillo-EspañaP. Villalobos-MolinaR. Estrada-SotoS. Anxiolytic-like effects and toxicological studies of Brickellia cavanillesii (Cass.) A. Gray in experimental mice models.J. Ethnopharmacol.2016192909810.1016/j.jep.2016.07.006 27381041
     [Google Scholar]
  35. OCDE_407. Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents.Paris, FranceOECD2008
     [Google Scholar]
  36. Cruz-TorresK. Estrada-SotoS. Arias-DuránL. Navarrete-VázquezG. Almanza-PérezJ. Mora-RamiroB. Perea-ArangoI. Hernández-NúñezE. Villalobos-MolinaR. Carmona-CastroG. Medina-DíazI.M. Ávila-VillarrealG. LC-MS Fingerprinting development for standardized precipitate from Agastache mexicana, which induces antihypertensive effect through NO production and calcium channel blockade.Pharmaceutics2023159234610.3390/pharmaceutics15092346 37765314
     [Google Scholar]
  37. AmacherD.E. A toxicologist’s guide to biomarkers of hepatic response.Hum. Exp. Toxicol.200221525326210.1191/0960327102ht247oa 12141396
     [Google Scholar]
  38. RamaiahS.K. A toxicologist guide to the diagnostic interpretation of hepatic biochemical parameters.Food Chem. Toxicol.20074591551155710.1016/j.fct.2007.06.007 17658209
     [Google Scholar]
  39. AwaadA.S. Al-JaberN.A. SolimanG.A. Al-OuthmanM.R. ZainM.E. MosesJ.E. El-MeligyR.M. New biological activities of Casimiroa edulis leaf extract and isolated compounds.Phytother. Res.201226345245710.1002/ptr.3690 22173732
     [Google Scholar]
  40. AwaadA.S. MaitlandD.J. MoneirS.M. New alkaloids from Casimiroa edulis fruits and their pharmacological activity.Chem. Nat. Compd.200743557658010.1007/s10600‑007‑0196‑9
     [Google Scholar]
  41. NagaiH. TanakaT. GotoT. KusudoT. TakahashiN. KawadaT. Phenolic compounds from leaves of Casimiroa edulis showed adipogenesis activity.Biosci. Biotechnol. Biochem.201478229630010.1080/09168451.2014.877821 25036684
     [Google Scholar]
  42. GuoL.Q. YamazoeY. Inhibition of cytochrome P450 by furanocoumarins in grapefruit juice and herbal medicines.Acta Pharmacol. Sin.2004252129136 14769198
     [Google Scholar]
  43. RizviS.H. KapilR.S. ShoebA. Alkaloids and coumarins of Casimiroa edulis.J. Nat. Prod.198548114610.1021/np50037a032 4009182
     [Google Scholar]
  44. MiL. LiY.C. SunM.R. ZhangP.L. LiY. YangH. A systematic review of pharmacological activities, toxicological mechanisms and pharmacokinetic studies on Aconitum alkaloids.Chin. J. Nat. Med.202119750552010.1016/S1875‑5364(21)60050‑X 34247774
     [Google Scholar]
  45. RenZ. ZhangH. WangZ. ChenX. YangL. JiangH. Progress in immunoassays of toxic alkaloids in plant-derived medicines: A review.Toxins202214316510.3390/toxins14030165 35324662
     [Google Scholar]
/content/journals/chddt/10.2174/011871529X346240250211090920
Loading
Vasorelaxant and Antihypertensive Effects of Extracts from the Leaves of Casimiroa edulis La Llave (Rutaceae) by NO Release and Calcium Channel Blockade
Cardiovasc Hematol Disord Drug Targets 25, 119 (2025); https://doi.org/10.2174/011871529X346240250211090920
/content/journals/chddt/10.2174/011871529X346240250211090920
/content/journals/chddt/10.2174/011871529X346240250211090920
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): antihypertensive; calcium channels blockade; Casimiroa edulis; nitric oxide; toxicity; vasorelaxation

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test