Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Mechanism of resveratrol-induced relaxation in the human gallbladder

Authors: Ching-Chung Tsai, Ming-Che Lee, Shu-Leei Tey, Ching-Wen Liu, Shih-Che Huang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

Resveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Resveratrol produces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Although resveratrol has been reported to cause relaxation of the guinea pig gallbladder, limited data are available about the effect of resveratrol on the gallbladder smooth muscle in humans. The purpose of this study was to investigate the relaxation effects of resveratrol in human gallbladder muscle strips.

Methods

We studied the relaxant effects of resveratrol in human gallbladder. In addition, we also investigated mechanism of resveratrol-induced relaxation in human gallbladder by tetraethylammonium (a non-selective potassium channels blocker), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channel), glibenclamide (an ATP-sensitive potassium channel blocker), charybdotoxin (an inhibitor of large conductance calcium-activated potassium channels and slowly inactivating voltage-gated potassium channels), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-Nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na+ channel blocker), and ω-conotoxin GVIA (a selective neuronal Ca2+ channel blocker).

Results

The present study showed that resveratrol has relaxant effects in human gallbladder muscle strips. In addition, we found that resveratrol-induced relaxation in human gallbladder is associated with nitric oxide, ATP-sensitive potassium channel, and large conductance calcium-activated potassium channel pathways.

Conclusions

This study provides the first evidence concerning the relaxant effects of resveratrol in human gallbladder muscle strips. Furthermore, these results demonstrate that resveratrol is a potential new drug or health supplement in the treatment of biliary colic.
Literature
1.
2.
Mattivi FZ. Solid phase extraction of trans-resveratrol from wines for HPLC analysis. Lebensm Unters Forsch. 1993;196:522–5.CrossRef
3.
Guerrero RF, García-Parrilla MC, Puertas B, Cantos-Villar E. Wine, resveratrol and health: a review. Nat Prod Commun. 2009;4:635–58.PubMed
4.
Zordoky BN, Robertson IM, Dyck JR. Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases. Biochim Biophys Acta. 2015;1852:1155–77.
5.
6.
Diaz-Gerevini GT, Repossi G, Dain A, Tarres MC, Das UN, Eynard AR. Beneficial action of resveratrol: how and why? Nutrition. 2016;32:174–8.CrossRefPubMed
7.
Colli A, Conte D, Valle SD, Sciola V, Fraquelli M. Meta-analysis: nonsteroidal anti-inflammatory drugs in biliary colic. Aliment Pharmacol Ther. 2012;35:1370–8.CrossRefPubMed
8.
Henderson SO, Swadron S, Newton E. Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. J Emerg Med. 2002;23:237–41.CrossRefPubMed
9.
Ness J, Hoth A, Barnett MJ, Shorr RI, Kaboli PJ. Anticholinergic medications in community-dwelling older veterans: prevalence of anticholinergic symptoms, symptom burden, and adverse drug events. Am J Geriatr Pharmacother. 2006;4:42–51.CrossRefPubMed
10.
Kline LW, Karpinski E. The resveratrol-induced relaxation of cholecystokinin octapeptide- or KCl-induced tension in male guinea pig gallbladder strips is mediated through L-type Ca2+ channels. J Neurogastroenterol Motil. 2015;21:62–8.
11.
Wang LD, Qiu XQ, Tian ZF, Zhang YF, Li HF. Inhibitory effects of genistein and resveratrol on guinea pig gallbladder contractility in vitro. World J Gastroenterol. 2008;14:4955–60.CrossRefPubMedPubMedCentral
12.
Jing F, Liu M, Yang N, Liu Y, Li X, Li JJ. Relaxant effect of chloroquine in rat ileum: possible involvement of nitric oxide and BKCa. Pharm Pharmacol. 2013;65:847–54.CrossRef
13.
Huang SC. Endothelin A receptors mediate relaxation of guinea pig internal anal sphincter through cGMP pathway. Neurogastroenterol Motil. 2010;22:1009–16.
14.
Giangiacomo KM, Sugg EE, Garcia-Calvo M, Leonard RJ, McManus OB, Kaczorowski GJ, Garcia ML. Synthetic charybdotoxin-iberiotoxin chimeric peptides define toxin binding sites on calcium-activated and voltage-dependent potassium channels. Biochemistry. 1993;32:2363–70.CrossRefPubMed
15.
Wittekindt OH, Visan V, Tomita H, Imtiaz F, Gargus JJ, Lehmann-Horn F, Grissmer S, Morris-Rosendahl DJ. An apamin- and scyllatoxin-insensitive isoform of the human SK3 channel. Mol Pharmacol. 2004;65:788–801.CrossRefPubMed
16.
Weatherall KL, Goodchild SJ, Jane DE, Marrion NV. Small conductance calcium-activated potassium channels: from structure to function. Prog Neurobiol. 2010;91:242–55.CrossRefPubMed
17.
Zhang J, Halm ST, Halm DR. Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon. Am J Physiol Gastrointest Liver Physiol. 2012;303:G1322–34.CrossRefPubMedPubMedCentral
18.
Matsuda NM, Miller SM. Non-adrenergic non-cholinergic inhibition of gastrointestinal smooth muscle and its intracellular mechanism(s). Fundam Clin Pharmacol. 2010;24:261–8.CrossRefPubMed
19.
Novakovic A, Bukarica LG, Kanjuh V, Heinle H. Potassium channels-mediated vasorelaxation of rat aorta induced by resveratrol. Basic Clin Pharmacol Toxicol. 2006;99:360–4.CrossRefPubMed
20.
Nagaoka T, Hein TW, Yoshida A, Kuo L. Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels. Invest Ophthalmol Vis Sci. 2007;48:4232–9.CrossRefPubMed
21.
Pullen C, Coulson FR, Fenning A. Effects of resveratrol and nebivolol on isolated vascular and cardiac tissues from young rats. Adv Pharmacol Sci. 2014;2014:720386.PubMedPubMedCentral
22.
Furfine ES, Harmon MF, Paith JE, Garvey EP. Selective inhibition of constitutive nitric oxide synthase by L-NG-nitroarginine. Biochemistry. 1993;32:8512–7.CrossRefPubMed
23.
Garvey EP, Tuttle JV, Covington K, Merrill BM, Wood ER, Baylis SA, Charles IG. Purification and characterization of the constitutive nitric oxide synthase from human placenta. Arch Biochem Biophys. 1994;311:235–41.CrossRefPubMed
24.
Murthy KS, Teng B, Jin J, Makhlouf GM. G protein-dependent activation of smooth muscle eNOS via natriuretic peptide clearance receptor. Am J Phys. 1998;275:C1409–16.
25.
Teng B, Murthy KS, Kuemmerle JF, Grider JR, Sase K, Michel T, Makhlouf GM. Expression of endothelial nitric oxide synthase in human and rabbit gastrointestinal smooth muscle cells. Am J Phys. 1998;275:G342–51.
26.
Makhlouf GM, Murthy KS. Smooth muscle of the gut. In: Podolsky DK, Camilleri M, Fitz JG, Kalloo AN, Shanahan F, Wang TC, editors. Yamada's textbook of gastroenterology. Hoboken: Wiley-Blackwell; 2016. p. 276–8.
27.
28.
Protić D, Beleslin-Čokić B, Spremović-Rađenović S, Radunović N, Heinle H, Sćepanović R, Gojković Bukarica L. The different effects of resveratrol and naringenin on isolated human umbilical vein: the role of ATP-sensitive K+ channels. Phytother Res. 2014;28:1412–8.CrossRefPubMed
29.
Dalaklioglu S, Ozbey G. Role of different types of potassium channels in the relaxation of corpus cavernosum induced by resveratrol. Pharmacogn Mag. 2014;10:47–52.CrossRefPubMedPubMedCentral
Metadata
Title
Mechanism of resveratrol-induced relaxation in the human gallbladder
Authors
Ching-Chung Tsai
Ming-Che Lee
Shu-Leei Tey
Ching-Wen Liu
Shih-Che Huang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1752-x

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue

Research article

Bacopa monnieri extract increases rat coronary flow and protects against myocardial ischemia/reperfusion injury

Research article

Anti-inflammatory and immuno-modulatory studies on LC-MS characterised methanol extract of Gentiana kurroo Royle

Research article

Inhibitory activities of selected Sudanese medicinal plants on Porphyromonas gingivalis and matrix metalloproteinase-9 and isolation of bioactive compounds from Combretum hartmannianum (Schweinf) bark

Research article

Centella asiatica modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC’s)

Research article

Anti-inflammatory evaluation of the methanolic extract of Taraxacum officinale in LPS-stimulated human umbilical vein endothelial cells

Research article

Methanol extract of Dicranopteris linearis L. leaves impedes acetaminophen-induced liver intoxication partly by enhancing the endogenous antioxidant system