It has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4-(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1) derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10,15, 20 and 30 mg/Kg, i.v.) produced dose-dependent reduction in blood pressure. In isolated aorta and superior mesenteric artery rings, Oxime S1 induced endothelium-independent and concentration-dependent relaxations (10 −8 M to 10 −4 M). In addition, Oxime S1-induced vasorelaxations were attenuated by hydroxocobalamin or methylene blue in aorta and by PTIO or ODQ in mesenteric artery rings, suggesting a role for the nitric oxide (NO) pathway. Additionally, Oxime S1 (30 and 100 µM) significantly increased NO concentrations (13.9 ± 1.6 nM and 17.9 ± 4.1 nM, respectively) measured by nitric oxide microsensors. Furthermore, pre-contraction with KCl (80 mM) prevented Oxime S1-derived vasorelaxation in endothelium-denuded aortic rings. Of note, combined treatment with potassium channel inhibitors also reduced Oxime S1-mediated vasorelaxation suggesting OPEN ACCESSMolecules 2014, 19 9774 a role for potassium channels, more precisely K ir , K v and K ATP channels. We observed the involvement of BK Ca channels in Oxime S1-induced relaxation in mesenteric artery rings.In conclusion, these data suggest that the Oxime S1 induces hypotension and vasorelaxation via NO pathway by activating soluble guanylate cyclase (sGC) and K + channels.
BackgroundIn northeastern Brazil, grape pomace has become a potential alternative byproduct because of the recover phenolic compounds from the vinification process. Comparative analyses were performed between lyophilized extract of grape skins from pomace, described as fermented (FGS), and fresh, unfermented (UGS) grape skins to show the relevant brand’s composition upon the first maceration in winemaking.MethodsThe use of in vitro testing such as Folin-Ciocalteu’s, DPPH free radical scavenger and HPLC methods were performed to evidence antioxidant effect and phenolic compounds. Additionally, vascular reactivity studies were performed in third-order branches of rat superior mesenteric arteries, which were obtained and placed in organ baths containing Krebs-Henseleit solution, maintained at 37 °C, gassed with a mixture of 95% O2 and 5% CO2, and maintained at pH 7.4. The in situ formation of reactive oxygen species (ROS) was evaluated in small mesenteric rings using oxidative fluorescent dihydroethidium dye.ResultsWe found higher phenolic content and antioxidant activity in FGS when compared to UGS. HPLC analyses identified a significant number of phenolic compounds with antioxidant potential in both samples. The vasorelaxant effect induced by FGS was more potent than that induced by UGS, and the activity was attenuated after removal of vascular endothelium or by blockade of endothelium-derived relaxing factors, such as NO and EDHF.ConclusionsThe FGS extract may be a great source of natural polyphenol products with potent antioxidant effects and endothelium-dependent vasodilatory actions involving NO and EDHF pathways.
This work aimed to explore the cardiovascular effects induced by freeze-dried juice from Syzygium jambolanum (Lam.) DC fruits (JSJ). JSJ presented high polyphenol content and steroids. HPLC analysis revealed that 2,5-dihydroxybenzoic and caffeic acid were present in higher amounts in the JSJ extract. In rat, JSJ induces hypotension and vasodilatation in mesenteric arteries, with or without vascular endothelium. JSJ-mediated vasodilation response against contractions induced with KCl (60 mM) depolarizing solution was significantly lower than the responses induced by JSJ when evaluated against phenylephrine-induced contractions. To investigate the involvement of potassium channels we used Tyrode's solution with KCl (20 mM) or tetraethylammonium (1.0, 3.0, or 5.0 mM). In these conditions JSJ-induced effects were significantly attenuated. To investigate the potassium channel subtypes involved in the response, we used 4-aminopyridine, glibenclamide, BaCl2, and iberiotoxin. In the presence (simultaneous) of different potassium channel blockers we observed a significant attenuation of JSJ-induced effect. Inhibition was also observed when using BaCl2, glibenclamide, or 4-aminopyridine, separately. However, incubation with iberiotoxin did not promote changes in either maximum effect, or potency. We also evidenced a discrete participation of CaV channels in the JSJ-induced vasorelaxant effect. In addition, patch-clamp studies demonstrated that JSJ could activate potassium channels. In conclusion, JSJ promotes hypotension and vasorelaxation in rats, involving, at least, the activation of potassium channels.
Ethnopharmacological Relevance: The traditional herbal medicinal product Funchicórea® has been widely used in clinical practice for the treatment of intestinal colic and constipation in newborns. However, no scientific data on the herbal product to prove its efficacy is available. Aim of the Study: This study aimed to evaluate the laxative and spasmolytic actions of Funchicórea®. Materials and Methods: Wistar rats (Rattus norvegicus) and Swiss mice (Mus musculus) of both sex, were used. In vivo pharmacological assays were performed to evaluate the stimulating effect on the gastrointestinal tract, and in vitro studies to verify its spasmodic activity. Results: Funchicórea® increased the motility of the small intestine in male mice at doses of 100 mg/kg (161.66±14.86 %, n=6) and 200 mg/kg (151.04±17.17 %, n=6) compared to control (100.00±10.49 %, n=6). However, this drug did not induce any change in intestinal transit in female mice. The intestinal transit of male mice treated with loperamide (3 mg/kg/day, during three days) was reduced 66.25±7.49 % (n=8) compared to the control group (100.00±5.16%, n=8) and we observed the normalization of the intestinal transit in constipated animals treated with Funchicórea® 100 mg/Kg (98.42±6.33 %, and 200 mg/kg (99.32±8.47%, n=7). Similar results were observed in the quantification for 24 hours of male and female rats faeces constipated by loperamide (3 mg/kg/day three days), however, in both animals groups treated with Funchicórea® 100 mg/kg (1.24±2.90 g, male; 3.60±0.80 g, female, n=6) and 200 mg/Kg (8.70±2.01 g, male, 10.03±1.30 g, female, n=6) the levels of faeces returned to basal values compared to constipated group (4.01±1.43 g, male; 1.70±0.10 g, female, n=6). In addition, Funchicórea® (0.01-1000 μg/mL) elicited relaxation in rat ileum pre-contracted by KCl 40 mM (Emax=97.5±7.0 %, n=7) and carbachol (1 μM, Emax=100.0±7.0 %, n=7). Conclusion: The results obtained demonstrated that the herbal medicine Funchicórea® acts by stimulating the intestine of rats and mice and has spasmolytic activity in isolated rat ileum.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.