Browse > Article
http://dx.doi.org/10.1016/j.jgr.2016.12.011

Regulatory effects of saponins from Panax japonicus on colonic epithelial tight junctions in aging rats  

Dun, Yaoyan (Medical College of China Three Gorges University)
Liu, Min (Medical College of China Three Gorges University)
Chen, Jing (Medical College of China Three Gorges University)
Peng, Danli (Medical College of China Three Gorges University)
Zhao, Haixia (Medical College of China Three Gorges University)
Zhou, Zhiyong (Medical College of China Three Gorges University)
Wang, Ting (Medical College of China Three Gorges University)
Liu, Chaoqi (Medical College of China Three Gorges University)
Guo, Yuhui (Medical College of China Three Gorges University)
Zhang, Changcheng (Medical College of China Three Gorges University)
Yuan, Ding (Renhe Hospital of China Three Gorges University)
Publication Information
Journal of Ginseng Research / v.42, no.1, 2018 , pp. 50-56 More about this Journal
Abstract
Background: Saponins from Panax japonicus (SPJ) are the most abundant and main active components of P. japonicus, which replaces ginseng roots in treatment for many kinds of diseases in the minority ethnic group in China. Our previous studies have demonstrated that SPJ has the effects of anti-inflammation through the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-${\kappa}B$) signaling pathways. The present study was designed to investigate whether SPJ can modulate intestinal tight junction barrier in aging rats and further to explore the potential mechanism. Methods: Aging rats had been treated with different doses (10 mg/kg, 30 mg/kg, and 60 mg/kg) of SPJ for 6 mo since they were 18 mo old. After the rats were euthanized, the colonic samples were harvested. Levels of tight junctions (claudin-1 and occludin) were determined by immunohistochemical staining. Levels of proinflammatory cytokines (interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$) were examined by Western blot. NF-${\kappa}B$ and phosphorylation of MAPK signaling pathways were also determined by Western blot. Results: We found that SPJ increased the expression of the tight junction proteins claudin-1 and occludin in the colon of aging rats. Treatment with SPJ decreased the levels of interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$, reduced the phosphorylation of three MAPK isoforms, and inhibited the expression of NF-${\kappa}B$ in the colon of aging rats. Conclusion: The studies demonstrated that SPJ modulates the damage of intestinal epithelial tight junction in aging rats, inhibits inflammation, and downregulates the phosphorylation of the MAPK and $NF-{\kappa}B$ signaling pathways.
Keywords
inflammation; intestinal epithelial tight junction; mitogen-activated protein kinase; nuclear factor-${\kappa}B$; saponins from Panax japonicus;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Wang Q, Guo XL, Wells-Byrum D, Noel G, Pritts TA, Ogle CK. Cytokine-induced epithelial permeability changes are regulated by the activation of the p38 mitogen-activated protein kinase pathway in cultured Caco-2 cells. Shock 2008;29:531-7.   DOI
2 Segawa S, Fujiya M, Konishi H, Ueno N, Kobayashi N, Shigyo T, Kohgo Y. Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway. PLoS One 2011;6:e23278.   DOI
3 Mihaescu A, Santen S, Jeppsson B, Thorlacius H. P38 mitogen-activated protein kinase signalling regulates vascular inflammation and epithelial barrier dysfunction in an experimental model of radiation-induced colitis. Br J Surg 2010;97:226-34.   DOI
4 Yang S, Yu M, Sun L, Xiao W, Yang X, Zhang C, Ma Y, Yang H, Liu Y, Lu D. Interferon-gamma-induced intestinal epithelial barrier dysfunction by NFkappaB/HIF-1alpha pathway. J Interferon Cytokine Res 2014;34:195-203.   DOI
5 Shon WJ, Lee YK, Shin JH, Choi EY, Shin DM. Severity of DSS-induced colitis is reduced in Ido1-deficient mice with down-regulation of TLR-Myd88-NF-kB transcriptional networks. Sci Rep UK 2015;5:17305.   DOI
6 Ma TY, Iwamoto GK, Hoa NT, Akotia V, Pedram A, Boivin MA, Said HM. TNFalpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol 2004;286:G367-76.   DOI
7 Dammann K, Khare V, Lang M, Claudel T, Harpain F, Granofszky N, Evstatiev R, Williams JM, Pritchard DM, Watson A, et al. PAK1 modulates a PPARgamma/NF-kappaB cascade in intestinal inflammation. Biochim Biophys Acta 2015;1853:2349-60.   DOI
8 Guma M, Stepniak D, Shaked H, Spehlmann ME, Shenouda S, Cheroutre H, Vicente-Suarez I, Eckmann L, Kagnoff MF, Karin M. Constitutive intestinal NFkappa B does not trigger destructive inflammation unless accompanied by MAPK activation. J Exp Med 2011;208:1889-900.   DOI
9 Katz D, Hollander D, Said HM, Dadufalza V. Aging-associated increase in intestinal permeability to polyethylene glycol 900. Dig Dis Sci 1987;32:285-8.   DOI
10 Wijck K, Verlinden T, Dekker J, Buunman WA, Dejong CH, Lenuests K. Multisugar permeability test: a promising new tool for accurate gut permeability assessment in health and disease. Gastroenterology 2011;140:S88.
11 Hollander D, Tarnawski H. Aging-associated increase in intestinal absorption of macromolecules. Gerontology 1985;31:133-7.   DOI
12 Guigoz Y, Dore J, Schiffrina EJ. The inflammatory status of old age can be nurtured from the intestinal environment. Curr Opin Clin Nutr 2008;11: 13-20.   DOI
13 Rera M, Clark RI, Walker DW. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A 2012;109:21528-33.   DOI
14 Libina N, Berman JR, Kenyon C. Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 2003;115:489-502.   DOI
15 Al-Sadi R, Ye DM, Said HM, Ma TY. IL-1 beta-induced increase in intestinal epithelial tight junction permeability is mediated by MEKK-1 activation of canonical NF-kappa B pathway. Am J Pathol 2010;177:2310-22.   DOI
16 Chairez-Ramirez MH, Sanchez-Burgos JA, Gomes C, Moreno-Jimenez MR, Gonzalez-Laredo RF, Bernad-Bernad MJ, Medina-Torres L, Ramirez-Mares MV, Gallegos-Infante JA, Rocha-Guzman NE. Morphological and release characterization of nanoparticles formulated with poly (dl-lactide-co-glycolide) (PLGA) and lupeol: in vitro permeability and modulator effect on NF-kappaB in Caco-2 cell system stimulated with TNF-alpha. Food Chem Toxicol 2015;85:2-9.   DOI
17 Ulgherait M, Rana A, Rera M, Graniel J, Walker DW. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell Rep 2014;8: 1767-80.   DOI
18 Capaldo CT, Nusrat A. Cytokine regulation of tight junctions. Biochim Biophys Acta 2009;1788:864-71.   DOI
19 John BJ, Abulafi AM, Poullis A, Mendall MA. Chronic subclinical bowel inflammation may explain increased risk of colorectal cancer in obese people. Gut 2007;56:1034-5.   DOI
20 He S, Hou X, Xu X, Wan C, Yin P, Liu X, Chen Y, Shu B, Liu F, Xu J. Quantitative proteomic analysis reveals heat stress-induced injury in rat small intestine via activation of the MAPK and NF-kappaB signaling pathways. Mol Biosyst 2015;11:826-34.   DOI
21 Tran L, Greenwood-Van Meerveld B. Age-associated remodeling of the intestinal epithelial barrier. J Gerontol Ser A Biol Sci Med Sci 2013;68:1045-56.   DOI
22 He HB, Xu J, Xu YQ, Wan C, Yin P, Liu X, Chen Y, Shu B, Liu F, Xu J. Cardioprotective effects of saponins from Panax japonicus on acute myocardial ischemia against oxidative stress-triggered damage and cardiac cell death in rats. J Ethnopharmacol 2012;140:73-82.   DOI
23 Wei N, Yuan D, He HB, Xu YQ, Zhang CC, Wang T, Liu CQ, Liu GY. Saponins from Panax japonicas reduces myocardial infarction induced reactive oxygen species production and cardiomyocyte apoptosis via activation of the NRF-2 pathway. Adv Mater Res Switz 2014;881-883:339-46.   DOI
24 Wei N, Zhang CC, He HB, Wang T, Liu ZQ, Liu GY, Sun ZW, Zhou ZY, Bai CH, Yuan D. Protective effect of saponins extract from Panax japonicus on myocardial infarction: involvement of NF-kappa B, Sirt1 and mitogenactivated protein kinase signalling pathways and inhibition of inflammation. J Pharm Pharmacol 2014;66:1641-51.   DOI
25 Wang T, Di GJ, Yang L, Dun YY, Sun ZW, Wan JZ, Peng B, Liu CQ, Xiong GR, Zhang CC, et al. Saponins from Panax japonicus attenuate d-galactose-induced cognitive impairment through its anti-oxidative and anti-apoptotic effects in rats. J Pharm Pharmacol 2015;67:1284-96.   DOI
26 Mullin JM, Valenzano MC, Verrecchio JJ, Kothari R. Age- and diet-related increase in transepithelial colon permeability of Fischer 344 rats. Dig Dis Sci 2002;47:2262-70.   DOI
27 Forsyth CB, Banan A, Farhadi A, Fields JZ, Tang Y, Shaikh M, Zhang LJ, Engen PA, Keshavarzian A. Regulation of oxidant-induced intestinal permeability by metalloprotease-dependent epidermal growth factor receptor signaling. J Pharmacol Exp Ther 2007;321:84-97.   DOI
28 Pastorelli L, De Salvo C, Mercado JR, Vecchi M, Pizarro TT. Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics. Front Immunol 2013;4:280.
29 Al-Sadi R, Boivin M, Ma T. Mechanism of cytokine modulation of epithelial tight junction barrier. Front Biosci 2009;14:2765-78.
30 Madsen KL, Lewis SA, Tavernini MM, Hibbard J, Fedorak RN. Interleukin 10 prevents cytokine-induced disruption of t84 monolayer barrier integrity and limits chloride secretion. Gastroenterology 1997;113:151-9.   DOI
31 Wang SG, Hibberd ML, Pettersson S, Lee YK. Enterococcus faecalis from healthy infants modulates inflammation through MAPK signaling pathways. PLoS One 2014;9:e97523.   DOI
32 Guina T, Deiana M, Calfapietra S, Cabboi B, Maina M, Tuberoso CI, Leonarduzzi G, Gamba P, Gargiulo S, Testa G. The role of p38 MAPK in the induction of intestinal inflammation by dietary oxysterols: modulation by wine phenolics. Food Funct 2015;6:1218-28.   DOI
33 Hu CH, Xiao K, Luan ZS, Song J. Early weaning increases intestinal permeability, alters expression of cytokine and tight junction proteins, and activates mitogen-activated protein kinases in pigs. J Anim Sci 2013;91:1094-101.   DOI
34 Ihara E, Beck PL, Chappellaz M, Wong J, Medlicott SA, MacDonald JA. Mitogenactivated protein kinase pathways contribute to hypercontractility and increased Ca(2+) sensitization in murine experimental colitis. Mol Pharmacol 2009;75:1031-41.   DOI
35 Hollenbach E, Neumann M, Vieth M, Roessner A, Malfertheiner P, Naumann M. Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease. Regul Peptides 2004;122:22.
36 Rafferty BJ, Unger BL, Perey AC, Tammariello SP, Pavlides S, McGee DW. A novel role for the Rho-associated kinase, ROCK, in IL-1-stimulated intestinal epithelial cell responses. Cell Immunol 2012;280:148-55.   DOI
37 Jijon HB, Panenka WJ, Madsen KL, Parsons HG. Map kinases contribute to IL-8 secretion by intestinal epithelial cells via a posttranscriptional mechanism. Am J Physiol Cell Physiol 2002;283:C31-41.   DOI
38 Lei S, Cheng T, Guo Y, Li C, Zhang W, Zhi F. Somatostatin ameliorates lipopolysaccharide-induced tight junction damage via the ERKeMAPK pathway in caco2 cells. Eur J Cell Biol 2014;93:299-307.   DOI
39 Elamin E, Masclee A, Troost F, Pieters HJ, Keszthelyi D, Aleksa K, Dekker J, Jonkers D. Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: a combined in vivo and in vitro approach. PLoS One 2014;9:e107421.   DOI
40 Huang XZ, Li ZR, Zhu LB, Huang HY, Hou LL, Lin J. Inhibition of p38 mitogenactivated protein kinase attenuates butyrate-induced intestinal barrier impairment in a Caco-2 cell monolayer model. J Pediatr Gastroenterol Nutr 2014;59:264-9.   DOI