Vasorelaxant effect of sinensetin via the NO/sGC/cGMP pathway and potassium and calcium channels

Abstract

Orthosiphon stamineus Benth. (Lambiaceae) is an important traditional plant for the treatment of hypertension. Previous studies have demonstrated that the sinensetin content in O. stamineus is correlated with its vasorelaxant activity. However, there is still very little information regarding the vasorelaxant effect of sinensetin due to a lack of scientific studies. Therefore, the present study was designed to investigate the underlying mechanism of action of sinensetin in vasorelaxation using an in vitro precontraction aortic ring assay. The changes in the tension of the aortic ring preparations were recorded using a force-displacement transducer and the PowerLab system. The mechanisms of the vasorelaxant effect of sinensetin were determined in the presence of antagonists. Sinensetin caused relaxation of the aortic ring precontracted with PE in the presence and absence of the endothelium and with potassium chloride in endothelium-intact aortic rings. In the presence of Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), methylene blue (cyclic guanosine monophosphate lowering agent), ODQ (selective soluble guanylate cyclase inhibitor), indomethacin (a nonselective cyclooxygenase inhibitor), tetraethylammonium (nonselective calcium activator K channel blocker), 4-aminopyridine (voltage-dependent K channel blocker), barium chloride (inwardly rectifying K channel blocker), glibenclamide (nonspecific ATP-sensitive K channel blocker), atropine (muscarinic receptor blocker), or propranolol (β-adrenergic receptor blocker), the relaxation stimulated by sinensetin was significantly reduced. Sinensetin was also active in reducing Ca release from the sarcoplasmic reticulum (via IPR) and in blocking calcium channels (VOCC). The present study demonstrates the vasorelaxant effect of sinensetin, which involves the NO/sGC/cGMP and indomethacin pathways, calcium and potassium channels, and muscarinic and beta-adrenergic receptors.

A Review on the Potential Use of Medicinal Plants From Asteraceae and Lamiaceae Plant Family in Cardiovascular Diseases

“…The extract showed remarkable anti-superoxide anion formation by inhibiting the activity with an IC 50 value of 0.51 mg/mL. In inhibiting lipid peroxidation, the extract exhibited a (Matsubara et al, 1999;Akowuah et al, 2005;Yam et al, 2016;Yam et al, 2018) Phlomoides strong inhibitory capacity and potent scavenging property (IC 50 , 15 mg/mL) compared to a-tocopherol (IC 50 , 3 mg/mL) (Citoglu et al, 2004). The antioxidant activity of methanolic extract of aerial part of C. crepidioides (Benth.)…”

“…Orthosiphon aristatus (Blume) Miq. contains sinensetin (17), which is essential for vasorelaxation activity (Yam et al, 2016;Yam et al, 2018). The studies measured the vasorelaxant effect of the compound by conducting a pre-contraction aortic ring assay.…”

“…The pathways that were involved in this vasorelaxant activity were NO/sGC/cGMP pathways. Sinensetin (17) at a dose of 0.262 µg/mL caused the vasodilatory effect (Yam et al, 2016;Yam et al, 2018).…”

Sinensetin: An Insight on Its Pharmacological Activities, Mechanisms of Action and Toxicity

“…Vasorelaxant effect of sinensetin was reported by Yam et al (2018) recently, employing in vitro pre-contraction aortic ring assay. It was suggested that the mechanism of action might be via NO/sGC/cGMP and indomethacin pathways, potassium and calcium channels, and muscarinic and beta-adrenergic receptors.…”

“…Diuretic A1-R-active ligand with pK i value and hill slope of 5.5 and 0.9 respectively comparable to luteolin (pK i 5.4 ± 0.2, hill slope 1.3) and quercetin (pK i 5.8 ± 0.1, hill slope 1.1) Yam et al (2018) compounds (Wilkens, 2015). Potent and nontoxic P-gp inhibitors are needed to increase drug accumulation and reversal of drug resistance (Leonard et al, 2003).…”