Abstract
We evaluated the effect of SKI3246, the 50 % ethanol extract of the rhizome of Atractylodes japonica, on visceral hypersensitivity, which is a major characteristic feature of IBS. We used various rat models of visceral hypersensitivity to assess the visceral pain responses to colorectal distension (CRD) in comparison with conventional IBS treatments. Oral administration of SKI3246 dose-dependently and significantly attenuated the abdominal withdrawal reflex (AWR) score in a model of acetic acid-induced visceral hypersensitivity. We also found that it reduced the number of abdominal contractions in response to CRD in a model of 2,4,6-trinitrobenzenesulfonic acid-induced visceral hypersensitivity, which was comparable to ramosetron or alosetron. Furthermore, treatment with SKI3246 also increased the pain threshold and abolished the elevated AWR scores to CRD in a rat model of neonatal maternal separation. We presumed that the modulation of the NK2 receptor is involved in the inhibitory activity of SKI3246 on the basis that it significantly inhibited the contraction of the distal colonic muscle induced by neurokinin A, the NK2 receptor agonist. The present results indicate that SKI3246 has the potential to be an effective therapeutic agent for IBS, especially insofar as it can relieve visceral hypersensitivity.
Similar content being viewed by others
References
Al-Chaer, E.D., M. Kawasaki, and P.J. Pasricha. 2000. A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology 119: 1276–1285.
Bouin, M., V. Plourde, M. Boivin, M. Riberdy, F. Lupien, M. Laganière, P. Verrier, and P. Poitras. 2002. Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds. Gastroenterology 122: 1771–1777.
Bueno, L., and J. Fioramonti. 2002. Visceral perception: Inflammatory and non-inflammatory mediators. Gut 51: i19–i23.
Chang, L., W.D. Chey, L. Harris, K. Olden, C. Surawicz, and P. Schoenfeld. 2006. Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: Systematic review of clinical trials and post-marketing surveillance data. The American Journal of Gastroenterology 101: 1069–1079.
Coutinho, S.V., P.M. Plotsky, M. Sablad, J.C. Miller, H. Zhou, A.I. Bayati, J.A. Mcroberts, and E.A. Mayer. 2002. Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. American Journal of Physiology 282: G307–G316.
Drossman, D.A., M. Camilleri, E.A. Mayer, and W.E. Whitehead. 2002. AGA technical review on irritable bowel syndrome. Gastroenterology 123: 2108–2131.
Dupont, A.W. 2007. Post-infectious irritable bowel syndrome. Current gastroenterology reports 9: 378–384.
Eutamene, H., S. Bradesi, M. Larauche, V. Theodorou, C. Beaufrand, J. Fioramonti, M. Cohen, A.P. Bryant, C. Kurtz, M.G. Currie, E.A. Meyer, and L. Bueno. 2010. Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. Neurogastroenterology and Motility 22: 312–384.
Hosseini, J.M., J.M. Goldhill, C. Bossone, V. Pineiro-Carrero, and T. Shea-Donohue. 1999. Progressive alterations in circular smooth muscle contractility in TNBS-induced colitis in rats. Neurogastroenterology and Motility 11: 347–356.
Jeong, S.I., S.Y. Kim, S.J. Kim, B.S. Hwang, T.H. Kwon, K.Y. Yu, S.H. Hang, K. Suzuki, and K.J. Kim. 2010. Antibacterial activity of phytochemicals isolated from Atractylodes japonica against methicillin-resistant Staphylococcus aureus. Molecules 15: 7395–7402.
Julia, V., O. Morteau, and L. Bueno. 1994. Involvement of neurokinin 1 and 2 receptors in viscerosensitive response to rectal distension. Gastroenterology 107: 94–102.
Kano, Y., K. Komatsu, K. Saitoi, H. Bando, and T. Sakurai. 1989. A new polyacetylene compound from atractylodes rhizome. Chemical & Pharmaceutical Bulletin 37: 193–194.
Kitajima, J., A. Kamoshita, T. Ishikawa, A. Takano, T. Fukuda, S. Isoda, and Y. Ida. 2003. Glycosides of Atractylodes japonica. Chemical & Pharmaceutical Bulletin 51: 152–157.
Konno, C., Y. Suzuki, K. Oishi, E. Munakata, and H. Hikino. 1985. Isolation and hypoglycemic activity of Atractans A, B and C, Glycans of <EM EMTYPE=. Planta Medica 51: 102–103.
La, J.H., T.W. Kim, T.S. Sung, J.W. Kang, H.J. Kim, and I.S. Yang. 2003. Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis. World Journal of Gastroenterology 9: 2791–2795.
Lee, K.J., N.Y. Kim, J.K. Kwon, K.C. Huh, O.Y. Lee, J.S. Lee, S.C. Choi, C.I. Sohn, S.J. Myung, H.J. Park, M.K. Choi, Y.T. Bak, and P.L. Rhee. 2011. Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: A multicenter, randomized clinical trial, compared with mebeverine. Neurogastroenterology and Motility 23: 1098–1104.
Lim, H., J.H. Lee, J. Kim, Y.S. Kim, and H.P. Kim. 2012. Effects of the rhizomes of Atractylodes japonica and atractylenolide I on allergic response and experimental atopic dermatitis. Archives of Pharmacal Research 35: 2007–2012.
Maggi, C.A. 1997. Tachykinins as peripheral modulators of primary afferent nerves and visceral sensitivity. Pharmacological Research 36: 153–169.
Mayer, E.A., and S. Bradesi. 2003. Alosetron and irritable bowel syndrome. Expert Opinion on Pharmacotherapy 4: 2089–2098.
Mayer, E.A., and G.F. Gebhart. 1994. Basic and clinical aspects of visceral hyperalgesia. Gastroenterology 107: 271–293.
Morteau, O., T. Hachet, M. Caussette, and L. Bueno. 1994. Experimental colitis alters visceromotor response to colorectal distension in awake rats. Digestive Diseases and Sciences 39: 1239–1248.
Posserud, I., A. Ersryd, and M. Simrén. 2006. Functional findings in irritable bowel syndrome. World Journal of Gastroenterology 12: 2830–2838.
Ren, T.H., J. Wu, D. Yew, E. Ziea, L. Lao, W.K. Leung, B. Berman, P.J. Hu, and J.J. Sung. 2007. Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome. American Journal of Physiology 292: G849–G856.
Schwetz, I., J.A. Mcroberts, S.V. Coutinho, S. Bradesi, G. Gale, M. Fanselow, M. Million, G. Ohning, Y. Tache, P.M. Plotsky, and E.A. Mayer. 2005. Corticotropin-releasing factor receptor 1 mediates acute and delayed stress-induced visceral hyperalgesia in maternally separated Long-Evans rats. American Journal of Physiology 289: G704–G712.
Spiller, R.C. 2003. Postinfectious irritable bowel syndrome. Gastroenterology 124: 1662–1671.
Tanaka, T., A. Tanaka, A. Nakamura, K. Matsushita, A. Imanishi, S. Matsumoto-Okano, N. Inatomi, K. Miura, M. Toyoda, G. Mizojiri, and Y. Tsukimi. 2012. Effects of TAK-480, a novel tachykinin NK(2)-receptor antagonist, on visceral hypersensitivity in rabbits and ricinoleic acid-induced defecation in guinea pigs. Journal of Pharmacological Sciences 120: 15–25.
Toulouse, M., A.M. Coelho, J. Fioramonti, A. Lecci, C. Maggi, and L. Bueno. 2000. Role of tachykinin NK2 receptors in normal and altered rectal sensitivity in rats. British Journal of Pharmacology 129: 193–199.
Verne, G.N., M.E. Robinson, and D.D. Price. 2001. Hypersensitivity to visceral and cutaneous pain in the irritable bowel syndrome. Pain 93: 7–14.
Wu, H.G., H.R. Liu, Z.A. Zhang, E.H. Zhou, X.M. Wang, B. Jiang, Z. Shi, C.L. Zhou, L. Qi, and X.P. Ma. 2009. Electro-acupuncture relieves visceral sensitivity and decreases hypothalamic corticotropin-releasing hormone levels in a rat model of irritable bowel syndrome. Neuroscience Letters 465: 235–237.
Acknowledgments
This study was supported by a grant of the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea. (Grant Number: A120767).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Son, H.J., Jung, K., Park, Y.H. et al. Inhibitory effects of SKI3246, the rhizome extract of Atractylodes japonica, on visceral hypersensitivity in experimental irritable bowel syndrome rat models. Arch. Pharm. Res. 38, 642–649 (2015). https://doi.org/10.1007/s12272-014-0454-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-014-0454-x