Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: Evidence for the inhibition of angiotensin converting enzyme

• Published in: Journal of ethnopharmacology Vol. 134; no. 2; pp. 363 - 372
• Main Authors: Gasparotto Junior, Arquimedes, Gasparotto, Francielly Mourão, Lourenço, Emerson Luiz Botelho, Crestani, Sandra, Stefanello, Maria Elida Alves, Salvador, Marcos José, da Silva-Santos, José Eduardo, Marques, Maria Consuelo Andrade, Kassuya, Cândida Aparecida Leite
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 24-03-2011; Elsevier
• Subjects: ACE inhibitors; angiotensin I; Angiotensin I - antagonists & inhibitors; angiotensin II; Angiotensin-Converting Enzyme Inhibitors - analysis; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Antihypertensive Agents - analysis; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; antihypertensive effect; Biological and medical sciences; blood pressure; Blood Pressure - drug effects; carotid arteries; catheters; Dose-Response Relationship, Drug; Flavonol; fluorometry; General pharmacology; heart rate; Hypertension; Hypertension - drug therapy; Hypertension - metabolism; hypotension; intravenous injection; isoquercitrin; kaempferol; ketamine; Male; Medical sciences; oral administration; peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - metabolism; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phytotherapy; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plant Leaves; polyethylene; Quercetin - analogs & derivatives; Quercetin - analysis; Quercetin - pharmacology; Quercetin - therapeutic use; Rats; Rats, Inbred SHR; Rats, Wistar; Tropaeolaceae; Tropaeolum - chemistry; Tropaeolum majus; xylazine; Hypertension; Tropaeolaceae; Flavonol; Tropaeolum majus; ACE inhibitors; Ornamental crop; Cardiovascular disease; Extract; Flavonoid; Medicinal plant; Polyphenol; Peptidyl-dipeptidase A; Dicotyledones; Angiospermae; Glycoside; Enzyme; Pharmacognosy; Peptidases; Plant origin; Phenols; Flavone derivatives; Hydrolases; Peptidyl-dipeptidases; Antihypertensive agent; Spermatophyta; ACE inhibitor
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2010.12.026

The effects of extract, purified fraction and isoquercitrin, an active flavonol of T. majus were evaluated on MAP in rats. Our results revealed that the isoquercitrin-induced hypotension is an event dependent on the inhibition of angiotensin II generation by ACE.
Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic properties. In the present study, we assessed whether the hypotensive and/or antihypertensive mechanism of hydroethanolic extract (HETM), semi-purified fraction (TMLR) obtained from T. majus and the flavonoids isoquercitrin (ISQ) and kaempferol (KPF) can be mediated by their interaction with angiotensin converting enzyme (ACE).
Firstly, to evaluate changes in mean arterial pressure (MAP), different groups of normotensive and spontaneously hypertensive rats (SHR) were orally and intraduodenally treated with HETM (10–300mg/kg) and TMLR (12.5–100mg/kg) and intravenously treated with ISQ and KPF being later anesthetized with ketamine (100mg/kg) and xylazine (20mg/kg). The left femoral vein and the right carotid artery were isolated, and polyethylene catheters were inserted for ISQ and KPF (0.5–4mg/kg) administration and blood pressure recording, respectively. The plasmatic ACE activity was evaluated to indirect fluorimetry, in serum samples after orally treatment with HETM, TMLR, ISQ and KPF.
The oral administration of the HETM and its TMLR significantly reduced, in a dose-dependent manner, the MAP in both normotensive and SHR. In addition, these preparations significantly decreased the MAP for up to 3h after the administration of the extract. Additionally, the intravenous administration of ISQ, but not KPF, decreased MAP in rats. Otherwise, neither the extracts nor ISQ affected the heart rate. The oral administration of the HETM, TMLR or ISQ reduced ACE activity in serum samples at 90min after administration. Finally, the intravenous administration of ISQ caused a significant reduction in the hypertensive response to angiotensin I, but not angiotensin II in normotensive rats.
Our results show that the hypotensive effects caused by the HETM, as well as by its TMLR, may be associated with the high levels of the flavonoid ISQ found in this plant. In addition, ISQ-induced hypotension in rats is an event dependent on the inhibition of angiotensin II generation by ACE.