Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-15T13:21:00.778Z Has data issue: false hasContentIssue false

Effects of Si-Jun-Zi decoction polysaccharides on cell migration and gene expression in wounded rat intestinal epithelial cells

Published online by Cambridge University Press:  08 March 2007

L. Liu
Affiliation:
Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
L. Han
Affiliation:
Immunology Laboratory, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People's Republic of China
Daisy Y. L. Wong
Affiliation:
Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
Patrick Y. K. Yue
Affiliation:
Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
W. Y. Ha
Affiliation:
Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
Y. H. Hu
Affiliation:
Department of Biology, Science Faculty, Hong Kong Baptist University, Kowloon Tong, Hong Kong
P. X. Wang
Affiliation:
Immunology Laboratory, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People's Republic of China
Ricky N. S. Wong*
Affiliation:
Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Department of Biology, Science Faculty, Hong Kong Baptist University, Kowloon Tong, Hong Kong
*
*Corresponding author: Dr Ricky N. S. Wong, fax +852 3411 5995, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Si-Jun-Zi decoction (SJZD), a traditional Chinese herbal prescription, has been used clinically for treating patients with disorders of the digestive system. Previous studies indicated that the polysaccharides of SJZD (SJZPS) are the active components contributing towards its pharmacological effects in improving gastrointestinal function and immunity. However, the protective and restitutive effects on intestinal epithelial cells remain unknown. In the present study, SJZPS were first extracted and chemically characterized. Then their stimulatory and restitutive effects on intestinal epithelial cells (IEC-6 cells) were elicited by different in vitro models including migration of wounded IEC-6 cells and cell proliferation. Results indicated that SJZPS not only protects the cells against the harmful impairment of indomethacin but also enhances re-epithelialization of a wounded monolayer at an optimal dose of 100 μg/ml at 24 h incubation. To elucidate the modulatory effect of SJZPS on wounded IEC-6 cells at the molecular level, an oligonucleotide microarray was employed to study differential gene expression of SJZPS-treated IEC-6 cells and the candidate genes were validated by RT-PCR. There was increased expression of genes coding for ion channels and transporters, which are critical to cell migration and restoration of wounded intestinal cells, suggesting a possible mechanism for re-epithelialization. In conclusion, our data show for the first time that SJZPS can enhance intestinal restitution and protect against indomethacin-induced damage of intestinal epithelial cells. These findings provide new insight into the mechanism of action of a traditional Chinese herbal prescription, SJZD, in intestinal wound restitution.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2005

References

Bilato, C, Pauly, RR, Melillo, G, Monticone, R, Gorelick-Feldman, D, Gluzband, YA, Sollott, SJ, Ziman, B, Lakatta, EG & Crow, MT (1995) Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor. J Clin Invest 96, 19051915.CrossRefGoogle ScholarPubMed
Bjarnason, I, Hayllar, J, MacPherson, AJ & Russell, AS (1993) Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 104, 18321847.CrossRefGoogle ScholarPubMed
Bonham, M, Arnold, H, Montgomery, B & Nelson, PS (2002) Molecular effects of the herbal compound PC-SPES: identification of activity pathways in prostate carcinoma. Cancer Res 62, 39203924.Google ScholarPubMed
Cario, E, Jung, S, Harder D'Heureuse, J, Schulte, C, Sturm, A, Wiedenmann, B, Goebell, H, Dignass, AU (2000) Effects of exogenous zinc supplementation on intestinal epithelial repair in vitro. Eur J Clin Invest 30, 419428.CrossRefGoogle ScholarPubMed
Chang, R (2002) Bioactive polysaccharides from traditional Chinese medicine herb as anticancer adjuvants. J Altern Complement Med 8, 559565.CrossRefGoogle Scholar
Chen, C, England, S, Akopian, AN & Wood, JN (1998) A sensory neuron-specific, proton-gated ion channel. Neurobiology 95, 1024010245.Google ScholarPubMed
Chen, GZ & Fu, D (1996) Effect of jiawei sijunzi decoction on migrating myoelectric complex in 8 Gy irradiated rats. Zhongguo Zhong Xi Yi Jie He Za Zhi 16, 221223.Google ScholarPubMed
Chun, H, Shin, DH, Hong, BS, Cho, WD, Cho, HY & Yang, HC (2002) Biochemical properties of polysaccharides from black pepper. Biol Pharm Bull 25, 12031208.CrossRefGoogle ScholarPubMed
Curran, T & Vogt, P (1992) Transcriptional Regulation. New York: Cold Spring Harbor Press.Google Scholar
Dignass, AU & Podolsky, DK (1995) Growth factors and cytokinase in inflammatory bowel disease: injury and healing in the epithelium. In Inflammatory Bowel Diseases, pp. 375383 [Tygat, GNJ, Bartelsman, JFWM and Deventer van, SJH, editors]. Dordrecht: Kluwer Academic Publishers.Google Scholar
Ding, SZ, Lam, SK, Yuen, ST, Wong, BC, Hui, WM, Ho, J, Guo, X & Cho, CH (1998) Prostaglandin, tumor necrosis factor alpha and neutrophils: causative relationship in indomethacin-induced stomach injuries. Eur J Pharmacol 348, 257263.CrossRefGoogle ScholarPubMed
Fleischmann, BD, Fleischmann, BK, Punt, JA, Gaulton, G, Hashimoto, Y & Kotlikoff, MI (1993) Control of resting membrane potential by delayed rectifier potassium currents in ferret airway smooth muscle cells. J Physiol 469, 625638.CrossRefGoogle ScholarPubMed
Fyfe, GK, Quinn, A & Canessa, CM (1998) Structure and function of the Mec-ENaC family of ion channels. Semin Nephrol 18, 138151.Google ScholarPubMed
Guo, L, Dong, ND, Xiong, AB, Liu, ZY, Liu, CR & He, XC (2003) An experimental study on the prevention and treatment of postburn intestinal injury and bacterial translocation by Sijunzi decoction in scalded rats. Zhonghua Shao Shang Za Zhi 19, 8993.Google Scholar
Haranaka, K, Satomi, N, Sakurai, A, Haranaka, R, Okada, N & Kobay, M (1985) Antitumor activities and tumor necrosis factor producibility of traditional Chinese medicine and crude drug. Cancer Immunol Immunother 20, 15.CrossRefGoogle Scholar
Hegde, P, Qi, R, Abernathy, K, Gay, C, Dharap, S, Gaspard, R, Hughes, JE, Snesrud, E, Lee, N & Quackenbush, J (2000) Concise guide to cDNA microarray analysis. Biotechniques 29, 548562.CrossRefGoogle ScholarPubMed
Himmel, HM, Whorton, AR & Strauss, HC (1993) Intracellular calcium, currents, and stimulus-response coupling in endothelial cells. Hypertension 21, 112127.CrossRefGoogle ScholarPubMed
Hirai, SI, Ryseck, RP, Mechta, F, Bravo, R & Yaniv, M (1989) Characterization of junD: a new member of the jun proto-oncogene family. EMBO J 8, 14331439.CrossRefGoogle Scholar
Iizuka, N, Oka, M, Yamamoto, K, Tangoku, A, Miyamoto, K, Miyamoto, T, Uchimura, S, Hamamoto, Y & Okita, K (2003) Identification of common or distinct genes related to antitumor activities of a medicinal herb and its major component by oligonucleotide microarray. Int J Cancer 107, 666672.CrossRefGoogle ScholarPubMed
Kimura, RE, Arango, V, Lloyd-Still, J (1998) Indomethacin and pancreatic enzymes synergistically damage intestine of rats. Dig Dis Sci 43, 23222332.CrossRefGoogle ScholarPubMed
Kiyohara, H, Matsumoto, T & Yamada, H (2002) Intestinal immune system modulating polysaccharides in a Japanese herbal (Kampo) medicine, Juzen-Taiho-To. Phytomedicine 9, 614624.CrossRefGoogle Scholar
Lacy, ER (1988) Epithelial restitution in the gastrointestinal tract. J Clin Gastroenterol 10, 7277.CrossRefGoogle ScholarPubMed
Lamph, WW, Wamsley, P, Sassone-Corsi, P & Verma, IM (1988) Induction of proto-oncogene JUN/AP-1 by serum and TPA. Nature 334, 629631.CrossRefGoogle ScholarPubMed
Langmead, L & Rampton, DS (2001) Herbal treatment in gastrointestinal and liver disease–benefits and dangers. Aliment Pharmacol Ther 15, 12391252.CrossRefGoogle ScholarPubMed
Larkai, EN, Smith, JL, Lidsky, MD & Graham, DY (1987) Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic nonsteroidal anti-inflammatory drug use. Am J Gastroenterol 82, 11531158.Google ScholarPubMed
Li, L, Li, J, Rao, JN, Li, M, Bass, BL & Wang, JY (1999) Inhibition of polyamine synthesis induces p53 gene expression but not apoptosis. Am J Physiol Cell Physiol 276, C946C954.CrossRefGoogle Scholar
Li, L, Liu, L, Rao, JN, Esmaili, A, Strauch, ED, Bass, BL & Wang, JY (2002) JunD stabilization results in inhibition of normal intestinal epithelial cell growth through P21 after polyamine depletion. Gastroenterology 123, 764779.CrossRefGoogle ScholarPubMed
Lin, PF (1988) Antitumor effect of Actinidia chinensis polysaccharide on murine tumor. Zhongghua Zhong Liu Za Zhi 10, 441444.Google ScholarPubMed
Liu, L, Zhou, H, Wang, PX & Hu, YJ (2000) Influence of total polysaccharide extracted from Sijunzi decoction on the intestinal mucosa associated lymphoid tissues of mice. Zhougguo Mianyixue Zazhi 17, 204206.Google Scholar
Lowry, O, Rosebrough, NH, Farr, AL & Randall, RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193, 265275.CrossRefGoogle ScholarPubMed
McCormack, SA, Viar, MJ & Johnson, LR (1992) Migration of IEC-6 cells: a model for mucosal healing. Am J Physiol 263, G426G435.Google Scholar
McCormack, SA, Viar, MJ & Johnson, LR (1993) Polysaccharides are necessary for cell migration by a small intestinal crypt cell line. Am J Physiol 264, G367G374.Google Scholar
McCormack, SA, Blanner, PM, Zimmerman, BJ, Ray, R, Poppleton, HM, Patel, TB & Johnson, LR (1998) Polyamine deficiency alters EGF receptor distribution and signaling effectiveness in IEC-6 cells. Am J Physiol 274, C192C205.CrossRefGoogle ScholarPubMed
McCormack, SA, Ray, R, Blanner, PM & Johnson, LR (1999) Polyamine depletion alters the relationship of F-actin, G-actin, and thymosin beta 4 in migrating IEC-6 cells. Am J Physiol 276, C459C468.CrossRefGoogle ScholarPubMed
Miller, GL (1959) Use of dinitrosalicylic acid reagent for determination of reducing sugar. J Anal Chem 31, 426430.CrossRefGoogle Scholar
Moore, R, Carlson, S & Madara, JL (1989) Rapid barrier restitution in an in vitro model of intestinal epithelial injury. Lab Invest 60, 237244.Google Scholar
Moore, TM, Brough, GH, Babal, P, Kelly, JJ, Li, M & Stevens, T (1998) Store-operated calcium entry promotes shape change in pulmonary endothelial cells expressing Trp1. Am J Physiol 275, L574L582.Google ScholarPubMed
Mosmann, T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65, 5563.CrossRefGoogle ScholarPubMed
Nilius, B, Vianna, F & Droogmans, G (1997) Ion channels in vascular endothelium. Annu Rev Physiol 59, 145170.CrossRefGoogle ScholarPubMed
Ou, M (1993) Chinese–English Manual of Common-used Prescription in TCM. Guangdong: Guangdong Science & Technology Publishing House.Google Scholar
Pauly, RR, Bilato, C, Sollott, SJ, Monticone, R, Kelly, PT, Lakatta, EG & Crow, MT (1995) Role of calcium/calmodulin-dependent protein kinase II in the regulation of vascular smooth muscle cell migration. Circulation 91, 11071115.CrossRefGoogle Scholar
Price, MP, Lewin, GR & McIlwrath, SL (2000) The mammalian sodium channel BNC1 is required for normal touch sensation. Nature 407, 10071011.CrossRefGoogle ScholarPubMed
Putney, JWJ & Bird, GS (1993) The inositol phosphate–calcium signaling system in nonexcitable cells. Endocr Rev 14, 610631.CrossRefGoogle ScholarPubMed
Quaroni, A, Wands, J, Trelstad, RL & Isselbacher, KJ (1979) Epithelial cell cultures from rat small intestine: characterization by morphologic and immunologic criteria. J Cell Biol 80, 248265.CrossRefGoogle ScholarPubMed
Rao, JN, Li, L, Golovina, VA, Platoshyn, O, Strauch, ED, Yuan, JX & Wang, JY (2001) CA2+-RhoA signalling pathway required for polyamine-dependent intestinal epithelial cell migration. Am J Physiol Cell Physiol 280, C993C1007.CrossRefGoogle ScholarPubMed
Rao, JN, Platoshyn, O, Li, L, Guo, X, Golovina, VA, Yuan, JX & Wang, JY (2002) Activation of K + channels and increased migration of differentiated intestinal epithelial cells after wounding. Am J Physiol Cell Physiol 282, C885C898.CrossRefGoogle ScholarPubMed
Ryder, K, Lanahan, A, Perez-Albuerne, E & Nathans, D (1989) Jun-D: a third member of the jun gene family. Proc Natl Acad Sci USA 86, 15001503.CrossRefGoogle ScholarPubMed
Sadava, D, Ahn, J, Zhan, M, Pang, ML, Ding, J & Kane, SE (2002) Effects of four Chinese herbal extracts on drug-sensitive and multidrug-resistant small-cell lung carcinoma cells. Cancer Chemother Pharmacol 49, 261266.CrossRefGoogle ScholarPubMed
Silen, W (1987) Gastric mucosal defense and repair Physiology of the Gastrointestinal Tract, pp. 10551069 [Johnson, LR and Christense, J, editors]. New York: Raven Press.Google Scholar
Staub, AM (1965) Removal of proteins–Sevag method. Methods Carbohydr Chem 5, 56.Google Scholar
Tarnawski, A, Tanoue, K, Santos, AM & Sarfen, IJ (1995) Cellular and molecular mechanisms of gastric ulcer healing. Is the quality of mucosal scar affected by treatment? Scand J Gastroenterol 210, 914.Google ScholarPubMed
Tsien, RW & Tsien, RY (1990) Calcium channels, stores, and oscillations. Annu Rev Cell Biol 6, 715760.CrossRefGoogle ScholarPubMed
Waldmann, R & Lazdunski, M (1998) H(+)-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. Curr Opin Neurobiol 8, 418424.CrossRefGoogle ScholarPubMed
Wang, JY, Wang, J, Golovina, VA, Li, L, Platoshyn, O & Yuen, JXJ (2000) Role of K + channel expression in polyamine-dependent intestinal epithelial cell migration. Am J Physiol Cell Physiol 278, C303C314.CrossRefGoogle ScholarPubMed
Watanabe, CM, Wolffram, S, Ader, P, Rimbach, G, Packer, L, Maguire, JJ, Schultz, PG & Gohil, K (2001) The in vivo neuromodulatory effects of the herbal medicine Ginkgo biloba. Proc Natl Acad Sci USA 98, 65776580.CrossRefGoogle ScholarPubMed
Xu, HM, Xie, ZH & Zhang, WY (1994) Immuomodulatory function of polysaccharide of Hericium erinaceus. Zhongguo Zhong Xi Yi Jie He Za Zhi 14, 427428.Google Scholar
Zhao, AG, Zhao, HL, Jin, XJ, Yang, JK & Tang, LD (2002) Effects of Chinese Jianpi herbs on cell apoptosis and related gene expression in human gastric cancer grafted onto nude mice. World J Gastroenterol 8, 792796.CrossRefGoogle ScholarPubMed
Zhong, WR, Huang, YX & Cui, JP (1997) Clinical study on modified sijunzi decoction in treating intestinal metaplasia of gastric mucosa. Zhongguo Zhong Xi Yi Jie He Za Zhi 17, 462464.Google ScholarPubMed