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

Resveratrol, as a polyphenolic compound that can be isolated from plants, and also a component of red wine has broad beneficial pharmacological properties. The aim was to investigate the role of nitric oxide and potassium channels in resveratrol-induced relaxation of human gastric smooth muscle. Gastric tissues were obtained from patients who underwent sleeve gastrectomy for severe obesity (n = 10 aged 21-48; BMI 48.21 ± 1.14). The mechanical activity from the muscle strips was detected under isometric conditions as the response to increasing concentrations of resveratrol before and after different pharmacological treatments. Resveratrol caused an observable, dose-dependent gastric muscle relaxation. The maximal response caused by the highest concentration of resveratrol was 83.49 ± 2.85% (p < 0.0001) of the control. Preincubation with L-NNA, L-NAME, or ODQ did not prevent the resveratrol-induced relaxation. Apamin, glibenclamide, 4AP or tamoxifen, did not inhibit the relaxing effect of resveratrol, as well. In turn, blocking BKCa by TEA, iberiotoxin, or charybdotoxin resulted in inhibition of resveratrol-induced relaxation (91.08 ± 2.07, p < 0.05; 95.60 ± 1.52, p < 0.01 and 89.58 ± 1.98, p < 0.05, respectively). This study provides the first observation that the relaxant effects of resveratrol in human gastric muscle strips occur directly through BKCa channels and independently of nitric oxide signaling pathways. Furthermore, there is considerable potential for further extensive clinical studies with resveratrol as an effective new drug or health supplement to treat gastrointestinal dyspepsia and other gastric hypermotility disorders.

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

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.

Phloroglucinol Strengthens the Antioxidant Barrier and Reduces Oxidative/Nitrosative Stress in Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is one of the most commonly occurring diseases within western dietary patterns. Usually untreated, it may lead to type 2 diabetes mellitus (T2DM), steatohepatitis (NASH), and hepatocellular carcinoma (HCC). Besides its severe aftermath, up to now, there is no known therapeutic approach to this disease in everyday clinical practice. Most NAFLD patients are encouraged to do physical activities or diet change and remain without pharmacological treatment. In this study, we present phloroglucinol (PHG) as a novel and promising compound in NAFLD treatment. PHG significantly increased the level of enzymatic and nonenzymatic antioxidants both in palmitate and hydrogen peroxide-induced oxidative stress models. Strengthened antioxidative defense reduced the oxidative/nitrosative damage to cell proteins, lipids, and carbohydrates. Furthermore, PHG treatment reduced hepatic steatosis; lowered inflammatory markers, such as NF-κB or HIF-1α; and inhibited cell apoptosis. Moreover, PHG had a more comprehensive effect than other commonly used antioxidants: N-acetylcysteine (NAC) and α-lipoic acid (ALA), suggesting its clinical usability. Therefore, our paper supports the benefits of natural compounds as a therapeutical approach to NAFLD.