isoquercitrin and Hypertension

Studies regarding the bioactivity of teas are mainly based on the phenolic composition and in vitro antioxidant activity of the herbal species used in their preparation. The aim of this study was to compare the in vitro and ex vivo antioxidant activity, cytotoxic/antiproliferative activity against cancer cells, the inhibitory activity of α-amylase, α-glucosidase and angiotensin I-converting enzymes, as well as the inhibition of DNA-induced fission of the peroxyl radical, in relation to aqueous extracts of Camellia sinensis var. sinensis (CS), Ilex paraguariensis (IP), Aspalathus linearis (AL) and an optimised extract (OT) containing the three herb species. A bivariate and multivariate statistical approach was employed to associate functional activities with individual phenolic composition. The CS and OT extracts showed the highest levels of hesperidin, quercetin-3-rutinoside, (-)-epigallocatechin-3-gallate and isoquercitrin. The CS and OT extracts showed the highest antioxidant activity, greater ability to inhibit α-amylase and proliferation of HCT8 cells, and greater ability to reduce Folin-Ciocalteu reagent. The AL extract, which is the major source of quercetin-3-rutinoside, hesperidin and isoquercitrin, showed the highest ability to inhibit α-glucosidase, the inhibition of LDL oxidation and protection of human erythrocytes. The IP extract showed the highest inhibition of lipoperoxidation in brain homogenate of Wistar rats, antihypertensive activity, and A549 cell proliferation; chlorogenic acid was its major phenolic compound. In general, the in vitro functionality of each extract was dependent on its chemical composition and the OT extract presented the most varied phenolic composition, and biological activity similar to the CS sample. In conclusion, the mixture of CS, AL, and IP represents a chemical and functional-based strategy to develop functional teas.

Topics: A549 Cells; alpha-Amylases; Angiotensins; Animals; Antioxidants; Aspalathus; Camellia sinensis; Catechin; Cell Line; Cholesterol, LDL; DNA Cleavage; Hesperidin; Humans; Hypertension; Ilex paraguariensis; Male; Oxygen Radical Absorbance Capacity; Phenols; Phytochemicals; Plant Extracts; Plant Leaves; Quercetin; Rats; Rats, Wistar; Rutin

Previous studies have shown that the extracts obtained from Tropaeolum majus L., and its main compound isoquercitrin (ISQ), exhibit pronounced diuretic effects, supporting the ethnopharmacological use of this plant. The aim of this study was to evaluate the efficacy and mechanisms underlying the diuretic action of an ethanolic extract of Tropaeolum majus (HETM), its purified fraction (TMLR), and its main compound ISQ, in spontaneously hypertensive rats (SHR).. The diuretic effects of HETM (300mg/kg; p.o.), TMLR (100mg/kg; p.o.), and ISQ (10mg/kg; p.o.), were compared with classical diuretics in 7days repeated-dose treatment. The urinary volume, sodium, potassium, chloride, bicarbonate, conductivity, pH and density were estimated in the sample collected for 15h. The plasmatic concentration of sodium, potassium, urea, creatinine, aldosterone, vasopressin, nitrite and angiotensin converting enzyme (ACE) activity were measured in samples collected at the end of the experiment (seventh day). Using pharmacological antagonists or inhibitors, we determine the involvement of bradykinin, prostaglandin and nitric oxide (NO) in ISQ-induced diuresis. In addition, reactive oxygen species (ROS) and the activity of erythrocytary carbonic anhydrase and renal Na(+)/K(+)/ATPase were evaluated in vitro.. HETM, TMLR and ISQ increased diuresis similarly to spironolactone and also presented K(+)-sparing effects. All groups presented both plasmatic aldosterone levels and ACE activity reduced. Previous treatment with HOE-140 (a B2-bradykinin receptor antagonist), or indomethacin (a cyclooxygenase inhibitor), or L-NAME (a NO synthase inhibitor), fully avoided the diuretic effect of ISQ. In addition, the 7days treatment with ISQ resulted in increased plasmatic levels of nitrite and reducing ROS production. Moreover, the renal Na(+)/K(+)/ATPase activity was significantly decreased by ISQ.. Our results suggest that the mechanisms through ISQ and extracts of Tropaeolum majus increase diuresis in SHR rats are mainly related to ACE inhibition, increased bioavailability of bradykinin, PGI2, and nitric oxide, besides an inhibitory effect on Na(+)/K(+)-ATPase.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Bradykinin; Disease Models, Animal; Diuresis; Diuretics; Epoprostenol; Ethanol; Hypertension; Male; Natriuresis; Nitric Oxide; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Quercetin; Rats; Rats, Inbred SHR; Signal Transduction; Sodium-Potassium-Exchanging ATPase; Solvents; Time Factors; Tropaeolum

Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic effects supporting the ethnopharmacological use of this plant as diuretic. In the present work, phytochemical investigation, guided by bio-assay in spontaneously hypertensive rats (SHR), was carried out in order to identify the compounds responsible for diuretic action.. Chromatographic fractionation of the hydroethanolic extract yielded an active fraction (TMLR) rich in isoquercitrin. TMLR (25-100mg/kg) and isoquercitrin (5-10mg/kg), as well the reference drug hydrochlorothiazide (10mg/kg) were orally administered in a single dose or daily for 7 days to SHR. The urine excretion rate, pH, density, conductivity and content of sodium (Na(+)) and potassium (K(+)) electrolytes were measured in the urine of saline-loaded animals.. The urinary excretion rate was dose-dependently increased in both TMLR and isoquercitrin groups, as well as Na(+). Despite the changes in urinary excretion of electrolytes, the plasmatic levels of Na(+) and K(+) had not been changed. In addition, we did not find any evidence of renal toxicity or other adverse effects in these animals, even after prolonged treatment with TMLR or isoquercitrin.. This research supports and extends the ethnomedicinal use of T. majus as diuretic. This activity seems to be associated to the presence of the flavonol isoquercitrin.

Topics: Animals; Diuretics; Dose-Response Relationship, Drug; Hydrochlorothiazide; Hypertension; Male; Phytotherapy; Plant Extracts; Plant Leaves; Potassium; Quercetin; Rats; Rats, Inbred SHR; Sodium; Tropaeolum; Urination

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 (10-300 mg/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 (0.5-4 mg/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 90 min 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.

Topics: Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Dose-Response Relationship, Drug; Hypertension; Male; Peptidyl-Dipeptidase A; Phytotherapy; Plant Extracts; Plant Leaves; Quercetin; Rats; Rats, Inbred SHR; Rats, Wistar; Tropaeolum

Enzymatically modified isoquercitrin (EMIQ) is a water-soluble glycoside of quercetin produced from rutin by enzymatic treatment. We investigated the anti-hypertensive effect of orally administered EMIQ in spontaneously hypertensive rats (SHR). The systolic blood pressure (SBP) in SHR administered EMIQ at a dose of 3 and 26 mg/kg/d was significantly lower than that in the control group on d 22, 36 and 50 of administration. The effect of EMIQ (26 mg/kg/d) was higher than equimolar administration of quercetin. Diltiazem administered as a positive control also suppressed the increase in SBP. and the effect was stronger than that of EMIQ. In the control group, the mean values of mean blood pressure (MBP) and diastolic blood pressure (DBP) were increased after the start of administration. Although diltiazem suppressed the increase in MBP, no significant changes were observed in the EMIQ groups. Compared with the control group, EMIQ groups showed the incidental changes of MBP and heart rate on day 22 of administration only. These results indicate that EMIQ suppressed the increase in SBP in SHR dose-dependently, and was more effective than the aglycone quercetin. It was also speculated that EMIQ showed higher anti-hypertensive effect than quercetin due to the high bioavailability, and the mechanism of SBP suppression is possibly through the improvement of endothelial NO production. In conclusion, our results suggest that EMIQ shows possibility as a naturally-derived safe food material which has an antihypertensive effect.

Topics: Analysis of Variance; Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Diltiazem; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Rate; Hypertension; Male; Quercetin; Rats; Rats, Inbred SHR; Time Factors