Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolites

J Ethnopharmacol. 2021 Feb 10:266:113399. doi: 10.1016/j.jep.2020.113399. Epub 2020 Sep 20.

Abstract

Ethnopharmacological relevance: Tagetes lucida Cav. commonly known as "yauhtli" or "pericón" is used in Mexican traditional medicine for the treatment of anxiety, depressant diseases, pain, hypertension, among others.

Aim: To evaluate the antihypertensive and vasorelaxant modes of action of a crude ethanolic extract from T. lucida aerial parts and to isolate the bioactive compounds.

Materials and methods: Ethanolic extract was tested in an in vivo assay in SHR rats by intragastric administration at 10 and 100 mg/kg dosages, to measure and to compare hemodynamic parameters like diastolic and systolic blood pressure and heart rate. Also, extract (3.03-1000 μg/ml), fractions (3.03-1000 μg/ml) and pure isolated compounds (1.75-550 μM) were evaluated on isolated aortic rings contracted with noradrenaline (0.1 μM) to determine their vasorelaxant effect and extract-mode of action.

Results: Ethanolic extract of T. lucida lowered systolic and diastolic blood pressure on SHR rats without heart rate modification (P > 0.05). Moreover, the extract showed concentration-dependent relaxant effect in a partially endothelium-dependent manner (P < 0.05), through NO/cGMP system activation and calcium channel blockade. 6,7,8-trimethoxycoumarin (1), 6,7-dimethoxycoumarin (2), and 7-methoxycoumarin (3) from T. lucida are the main bioactive compounds of the extract and showed significant vasorelaxant activity.

Conclusions: Results provide evidence and endorsed the antihypertensive properties attributed to T. lucida in traditional medicine, which is produced by vasorelaxant effect mainly through multitarget NO/cGMP system activation and calcium channel blockade. Coumarin derivatives 1, 2 and 3 are the responsible of the vasorelaxant activity.

Keywords: Antihypertensive; Calcium channel blockade; Coumarins; NO/cGMP system; Tagetes lucida; Vasorelaxant.

MeSH terms

  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / isolation & purification
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / isolation & purification
  • Calcium Channel Blockers / pharmacology
  • Cyclic GMP / metabolism
  • Dose-Response Relationship, Drug
  • Hypertension / drug therapy
  • Male
  • Medicine, Traditional
  • Nitric Oxide / metabolism
  • Plant Components, Aerial
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • Tagetes / chemistry*
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / isolation & purification
  • Vasodilator Agents / pharmacology*

Substances

  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Plant Extracts
  • Vasodilator Agents
  • Nitric Oxide
  • Cyclic GMP