Effects of Dehydroeffusol on Spasmogen-Induced Contractile Responses of Rat Intestinal Smooth Muscles

Abstract

Dehydroeffusol is a naturally occurring phenanthrene isolated from Juncus effusus. In the context of screening new drugs against gastrointestinal spasms, we investigated its effects on isolated rat jejunum in vitro. Dehydroeffusol (30–90 µM) slightly and transiently enhanced contractions in a concentration-dependent manner but significantly inhibited the contractions induced by KCl (100 mM), (±)-Bay-K8644 (5 µM), pilocarpine (90 µM), and histamine (100 µM). These results show that dehydroeffusol may antagonize the spasmogenic activity of various agents, and therefore, could be a promising agent in the treatment of spasms. Its potential spasmolytic mechanism is also discussed.

Key words

dehydroeffusol - rat jejunum - spasmolytic - smooth muscle - Juncus effusus - Juncuaceae

• References

• 1 Wang YG, Wang YL, Zhai HF, Liao YJ, Zhang B, Huang JM. Phenanthrenes from Juncus effusus with anxiolytic and sedative activities. Nat Prod Res 2012; 26: 1234-1239
• 2 Liao YJ, Zhai HF, Zhang B, Duan TX, Huang JM. Anxiolytic and sedative effects of dehydroeffusol from Juncus effusus in mice. Planta Med 2011; 77: 416-420
• 3 Kovacs A, Vasas A, Hohmann J. Natural phenanthrenes and their biological activity. Phytochemistry 2008; 69: 1084-1110
• 4 Estrada S, López-Guerrero J, Villalobos-Molina R, Mata R. Spasmolytic stilbenoids from Maxillaria densa . Fitoterapia 2004; 75: 690
• 5 Hernández-Romero Y, Rojas J, Castillo R, Rojas A, Mata R. Spasmolytic effects, mode of action, and structure-activity relationships of stilbenoids from Nidema boothii . J Nat Prod 2004; 67: 160
• 6 Estrada S, Rojas A, Mathison Y, Israel A, Mata R. Nitric oxide/cGMP mediates the spasmolytic action of 3,4′-dihydroxy-5,5′-dimethoxybibenzyl from Scaphyglottis livida . Planta Med 1999; 65: 109-114
• 7 Makharia GK. Understanding and treating abdominal pain and spasms in organic gastrointestinal diseases: Inflammatory bowel disease and biliary diseases. J Clin Gastroenterol 2011; 45 (Suppl.) S89-S93
• 8 Nasu T, Sasaki M. Effect of Mn²⁺ on the development of tension induced in guinea-pig taenia coli by Bay K8644. J Pharm Pharmacol 1998; 50: 311-315
• 9 Sanders KM, Koh SD, Ro S, Ward SM. Regulation of gastrointestinal motility–insights from smooth muscle biology. Nat Rev Gastroenterol Hepatol 2012; 9: 633-645
• 10 Somlyo AP, Somlyo AV. Smooth muscle: excitation-contraction coupling, contractile regulation, and the cross-bridge cycle. Alcohol Clin Exp Res 1994; 18: 138-143
• 11 Foster RW, Small RC, Weston AH. The spasmogenic action of potassium chloride in guinea-pig trachealis. Br J Pharmacol 1983; 80: 553-559
• 12 Karaki H, Satake N, Shibata S. Mechanism of barium-induced contraction in the vascular smooth muscle of rabbit aorta. Br J Pharmacol 1986; 88: 821-826
• 13 Unno T, Kwon SC, Okamoto H, Irie Y, Kato Y, Matsuyama H, Komori S. Receptor signaling mechanisms underlying muscarinic agonist-evoked contraction in guinea-pig ileal longitudinal smooth muscle. Br J Pharmacol 2003; 139: 337-350
• 14 Ragy M, Elbassuoni E. The role of nitric oxide and L-type calcium channel blocker in the contractility of rabbit ileum in vitro. J Physiol Biochem 2012; 68: 521-528
• 15 Hwang KS, Van Breemen C. Effects of the Ca agonist Bay K8644 on 45Ca influx and net Ca uptake into rabbit aortic smooth muscle. Eur J Pharmacol 1985; 116: 299-305
• 16 Morel N, Hardy JP, Godfraind T. Histamine-operated calcium channels in intestinal smooth muscle of the guinea-pig. Eur J Pharmacol 1987; 135: 69-75
• 17 Estrada-Soto S, López-Guerrero J, Villalobos-Molina R, Mata R. Endothelium-independent relaxation of aorta rings by two stilbenoids from the orchids Scaphyglottis livida . Fitoterapia 2006; 77: 236
• 18 Frishman WH. Drug therapy. Pindolol: a new beta-adrenoceptor antagonist with partial agonist activity. N Engl J Med 1983; 308: 940-944
• 19 Zhu HL, Hirst GD, Ito Y, Teramoto N. Modulation of voltage-dependent Ba²⁺ currents in the guinea-pig gastric antrum by cyclic nucleotide-dependent pathways. Br J Pharmacol 2005; 146: 129-138
• 20 Chen G, Zhu L, Liu Y, Zhou Q, Chen H, Yang J. Isoliquiritigenin, a flavonoid from licorice, plays a dual role in regulating gastrointestinal motility in vitro and in vivo . Phytother Res 2009; 23: 498-506
• 21 Liu Z, Gao W, Zhang J, Hu J. Antinociceptive and smooth muscle relaxant activity of Croton tiglium L seed: An in-vitro and in-vivo study. Iran J Pharm Res 2012; 11: 611-620
• 22 Bassil A, Häglund Y, Brown J, Rudholm T, Hellström P, Näslund E, Lee K, Sanger G. Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract. Br J Pharmacol 2007; 150: 58
• 23 Fernandez AI, Garcia de Boto MJ, Gutierrez M, Cantabrana B, Hidalgo A. Influence of hormonal status in relaxant effect of diethylstilbestrol and nifedipine on isolated rat uterus contraction. Gen Pharmacol 1995; 26: 1281-1287
• 24 Nasu T, Sasaki M, Shibata H. Long-lasting actions of Bay K 8644 on responses of guinea pig taenia coli. Gen Pharmacol 1998; 31: 43-45
• 25 Zhu L, Cui YY, Feng JM, Wu XJ, Chen HZ. Aceclidine and pilocarpine interact differently with muscarinic receptor in isolated rabbit iris muscle. Life Sci 2006; 78: 1617-1623
• 26 Piao H, Nagai S, Tsurumaki T, Niki T, Higuchi H. Potentiation by neuropeptide Y of histamine H₁ receptor-mediated contraction in rat blood vessels. Vascul Pharmacol 2007; 46: 260-270