Abstract
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.
Highlights
Resveratrol, as a naturally occurring bioactive molecule, has become a popular subject of scientific interest due to its potential benefit functions
One of the most interesting aspects of its future development as a promising drug is that resveratrol does not appear to have side effects at short-term dosages, and no major side effects have been found in long-term clinical trials
Our study aimed to investigate the role of nitric oxide and potassium channels in resveratrol-induced relaxation of human gastric smooth muscle
Summary
Resveratrol, as a naturally occurring bioactive molecule, has become a popular subject of scientific interest due to its potential benefit functions. Due to multiple pharmacological effects and promising results of preclinical studies, in many clinical trials over the past few years, oral supplementation with combinations of, inter alia, resveratrol has been introduced (Drygalski et al, 2018). The clinical use of resveratrol is considerably limited due to the low oral bioavailability caused by the short biological half-life, poor water solubility, and rapid metabolism (Palle and Neerati, 2017; Peng et al, 2018). Studies are conducted to achieve an effective serum concentration of this polyphenol to reach many of the proposed sites of action outside the gastrointestinal (GI) tract after an oral dose of 25 mg to even 5 g (Peng et al, 2018; Wang and Sang, 2018). Far little attention has been given to the relaxing effect of the human GI smooth muscle caused by resveratrol
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