Quercetin relaxes human gastric smooth muscles directly through ATP‐sensitive potassium channels and not depending on the nitric oxide pathway

Abstract

Background: Quercetin has recently become a remarkably popular subject of research due to its broad beneficial pharmacological properties. The goal of our study was to observe its effects on contractility of human gastric smooth muscles in reference to the NO pathway and direct influence of potassium channels.Methods: Tissues were obtained from patients undergoing sleeve gastrectomy due to morbid obesity (n = 10 aged 24-56; BMI 47.16 ± 1.84). The following parameters were evaluated in the recordings: area under the curve (AUC), average baseline muscle tone, and relative change in muscle contraction. Key Results: Quercetin induced noticeable, dose-dependent relaxation of the carbachol treated gastric strips. The substantial effect was noted at concentrations higher than 10 −7 mol/L and maximal at 10 −4 mol/L (81.82 ± 3.32%; n = 10; p < 0.0001) of the control.Neither NOS blockers nor guanylyl cyclase blockers had inhibitory effects on the relaxation of strips induced by examined polyphenol. Glibenclamide inhibited the relaxing effect of quercetin, significant at concentrations higher than 5⋅10 −5 mol/L. Preincubation with charybdotoxin or apamin extended the relaxing effect of quercetin (from 10 −6 mol/L).Tamoxifen, in turn, significantly increased muscle relaxation at all quercetin concentrations. Conclusions & Inferences:In conclusion, the current study was the first to show that quercetin-induced relaxation of human gastric smooth muscle occurs directly through K + ATP channels and independently to NO pathways. The present results suggest that quercetin is a potential nutraceutical in the treatment of functional gastrointestinal dyspepsia and other minor gastric muscle motility disturbance.

Ameliorative Effects of Humulus japonicus Extract and Polysaccharide-Rich Extract of Phragmites rhizoma in Rats with Gastrointestinal Dysfunctions Induced by Water Avoidance Stress

“…e present results agreed that GE was increased in WAS rats [37]. Quercetin of HJE relaxed the human gastric smooth muscle directly via potassium channels [38]. Galactose, active constituent of PEP, inhibited the GE of young pig initiated by an osmotic effect within the mucosa after absorption [39,40].…”

Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner

“…We found resveratrol concentration-dependently decreased human gastric muscle contractions in all concentrations used. Our finding is consistent with data reported for the influence of flavonoids on GI muscles ( Zhang et al, 2014 ; Modzelewska et al, 2021 ).…”

“…Resveratrol has been shown to relax various types of smooth muscle, including arteries ( Naderali et al, 2001 ; Shen et al, 2013 ; Choi et al, 2016 ; Breuss et al, 2019 ), umbilical vein ( Hassanpour et al, 2021 ), uterus ( Wu et al, 2015 ), gallbladder ( Kline and Karpinski, 2015 ), corpus cavernosum ( Soner et al, 2010 ) and GI tract ( Zhang et al, 2014 ; Parlar and Arslan, 2019 ; Modzelewska et al, 2021 ). In previous studies, doses were used in a fairly wide range, and due to the low oral bioavailability of resveratrol, an orally administered nutraceutical operated almost exclusively in the gastrointestinal tract ( Palle and Neerati, 2017 ; Peng et al, 2018 ).…”

“…The ability of NO to relax smooth muscles is well established ( Modzelewska et al, 2019 , Modzelewska et al, 2021 ; Idrizaj et al, 2021 ). One of the mechanisms of NO smooth muscle relaxation is the activation of soluble guanylyl cyclase (sGC) ( Friebe et al, 2018 ), which is expressed in a variety of cell types and signals through cGMP on to cGMP-dependent protein kinase (PKG), phosphodiesterases or, possibly, on to cGMP-regulated channels ( Friebe and Koesling, 2003 ).…”

“…There, too, no effect of blocking the NO pathway on gastric muscle relaxation was observed. ( Modzelewska et al, 2021 ). Thus, our findings indicate that resveratrol can cause the human gastric muscles to relax independently of the NO pathway.…”