Small conductance calcium-activated potassium channels and nitric oxide/cGMP pathway mediate cardioprotective effects of Croton urucurana Baill. In hypertensive rats

Lopes, Katiana Simões; Marques, Aline Aparecida Macedo; Moreno, Karyne Garcia Tafarelo; Lorençone, Bethânia Rosa; Leite, Patrícia Regina Terço; Silva, Gabriela Pereira da; Santos, Ariany Carvalho dos; Souza, Roosevelt Isaías Carvalho; Gasparotto, Francielly Mourão; Cassemiro, Nadla Soares; Lourenço, Emerson Luiz Botelho; Klider, Lislaine Maria; Budel, Jane Manfron; Silva, Denise Brentan

doi:10.1016/j.jep.2022.115255

Cited by 7 publications

(2 citation statements)

References 42 publications

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“…The SK channels play an important role in the cardioprotective effects of prolonged administration of an extract from leaves of Croton urucurana Baill. ( Euphorbiaceae ), which is popularly known as ‘sangue de dragão’, according to the spontaneously hypertensive rat model [ 149 ]. Flavonoids (including rutin, isoquercetin, kaempferol, vitexin) are the key bioactive substances in this extract [ 150 ].…”

Section: Calcium-activated Channels (Kca)mentioning

confidence: 99%

Flavonoids as Modulators of Potassium Channels

Richter

Trybek

Delfino

et al. 2023

IJMS

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Potassium channels are widely distributed integral proteins responsible for the effective and selective transport of K+ ions through the biological membranes. According to the existing structural and mechanistic differences, they are divided into several groups. All of them are considered important molecular drug targets due to their physiological roles, including the regulation of membrane potential or cell signaling. One of the recent trends in molecular pharmacology is the evaluation of the therapeutic potential of natural compounds and their derivatives, which can exhibit high specificity and effectiveness. Among the pharmaceuticals of plant origin, which are potassium channel modulators, flavonoids appear as a powerful group of biologically active substances. It is caused by their well-documented anti-oxidative, anti-inflammatory, anti-mutagenic, anti-carcinogenic, and antidiabetic effects on human health. Here, we focus on presenting the current state of knowledge about the possibilities of modulation of particular types of potassium channels by different flavonoids. Additionally, the biological meaning of the flavonoid-mediated changes in the activity of K+ channels will be outlined. Finally, novel promising directions for further research in this area will be proposed.

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Section: Calcium-activated Channels (Kca)mentioning

confidence: 99%

Flavonoids as Modulators of Potassium Channels

Richter

Trybek

Delfino

et al. 2023

IJMS

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“…The function of the vascular endothelium has clinical implications in pathologies such as cardiovascular disease, diabetes, and obesity [ 18 , 19 ]. Regarding the antihypertensive mechanisms postulated for the drugs currently in use, more than half depend on the vascular endothelium, acting on the NO/cGMP pathway, as Ca 2+ channel blockers or potassium channel activators [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Oxime Synthesized from a Natural Product of Senecio nutans SCh. Bip. (Asteraceae) Enhances Vascular Relaxation in Rats by an Endothelium-Independent Mechanism

et al. 2022

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Senecio nutans Sch. Bip. and its constituents are reported to have antihypertensive effects. We isolated metabolite–1, a natural compound from S. nutans (4-hydroxy-3-(isopenten-2-yl)-acetophenone), and synthesized novel oxime – 1 (4-hydroxy-3-(isopenten-2-yl)-acetophenoxime) to evaluate their effect on vascular reactivity. Compounds were purified (metabolite–1) or synthetized (oxime–1) and characterized using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). Using pharmacological agents such as phenylephrine (PE) and KCl (enhancing contraction), acetylcholine (ACh), L-NAME (nitric oxide (NO) and endothelial function), Bay K8644-induced CaV1.2 channel (calcium channel modulator), and isolated aortic rings in an organ bath setup, the possible mechanisms of vascular action were determined. Pre-incubation of aortic rings with 10−5 M oxime–1 significantly (p < 0.001) decreased the contractile response to 30 mM KCl. EC50 to KCl significantly (p < 0.01) increased in the presence of oxime–1 (37.72 ± 2.10 mM) compared to that obtained under control conditions (22.37 ± 1.40 mM). Oxime–1 significantly reduced (p < 0.001) the contractile response to different concentrations of PE (10−7 to 10−5 M) by a mechanism that decreases Cav1.2-mediated Ca2+ influx from the extracellular space and reduces Ca2+ release from intracellular stores. At a submaximal concentration (10−5 M), oxime–1 caused a significant relaxation in rat aorta even without vascular endothelium or after pre-incubate the tissue with L-NAME. Oxime–1 decreases the contractile response to PE by blunting the release of Ca2+ from intracellular stores and blocking of Ca2+ influx by channels. Metabolite–1 reduces the contractile response to KCl, apparently by reducing the plasma membrane depolarization and Ca2+ influx from the extracellular space. These acetophenone derivates from S. nutans (metabolite–1 and oxime–1) cause vasorelaxation through pathways involving an increase of the endothelial NO generation or a higher bioavailability, further highlighting that structural modification of naturally occurring metabolites can enhance their intended pharmacological functions.

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