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Catalpol reduces the production of inflammatory mediators via PPAR-γ activation in human intestinal Caco-2 cells

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Abstract

Catalpol, a major iridoid glycoside present in Rehmannia glutinosa, has been reported to show a variety of pharmacological properties. However, the molecular mechanism underlying the anti-inflammatory effect of catalpol in intestinal cells remains poorly understood. The present study was aimed at investigating the effects of catalpol on the production of inflammatory mediators and its underlying signaling pathways in human intestinal Caco-2 cells. Catalpol significantly inhibited IL-1β-induced mRNA synthesis and protein production of pro-inflammatory cytokines, including IL-6, IL-8, and MCP-1. Further investigation of the molecular mechanism revealed that the anti-inflammatory effect of catalpol in Caco-2 cells is similar to that of troglitazone—a synthetic peroxisome proliferator-activated receptor (PPAR)-γ agonist—on intestinal inflammation mediated by PPAR-γ activation. These findings suggest that the clinical application of medicinal plants that contain catalpol may lead to a partial prevention of intestinal inflammation.

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References

  1. Monteleone I, Vavassori P, Biancone L, Monteleone G, Pallone F (2002) Immunoregulation in the gut: success and failures in human disease. Gut 50:iii60–iii64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tan NS, Michalik L, Desvergne B, Wahli B (2005) Multiple expression control mechanisms of peroxisome proliferator-activated receptors and their target genes. J Steroid Biochem Mol Biol 93:99–105

    Article  CAS  PubMed  Google Scholar 

  3. Tsao WC, Wu HM, Chi KH, Chang YH, Lin WW (2005) Proteasome inhibitors induce peroxisome proliferator-activated receptor transactivation through RXR accumulation and a protein kinase C-dependent pathway. Exp Cell Res 304:234–243

    Article  CAS  PubMed  Google Scholar 

  4. Terrasi M, Bazan V, Caruso S, Insalaco L, Amodeo V, Fanale D, Corsini LR, Contaldo C, Mercanti A, Fiorio E, Lo Re G, Cicero G, Surmacz E, Russo A (2013) Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells. J Cell Physiol 228:1368–1374

    Article  CAS  PubMed  Google Scholar 

  5. Celinski K, Dworzanski T, Korolczuk A, Piasecki R, Slomka M, Madro A, Formal R (2011) Effects of peroxisome proliferator-activated receptors-γ ligands on dextran sodium sulphate-induced colitis in rats. J Physiol Pharmacol 62:347–356

    CAS  PubMed  Google Scholar 

  6. Celinski K, Dworzanski T, Korolczuk A, Slomka M, Radej S, Cichoz-Lach H, Madro A (2011) Activated and inactivated PPARs-γ modulate experimentally induced colitis in rats. Med Sci Monit 17: BR116–BR124

  7. Borniquel S, Jansson EA, Cole MP, Freeman BA, Lundberg JO (2010) Nitrated oleic acid up-regulates PPARγ and attenuates experimental inflammatory bowel disease. Free Radic Biol Med 48:499–505

    Article  CAS  PubMed  Google Scholar 

  8. Sánchez-Hidalgo M, Martín AR, Villegas I, de la Lastra CA (2007) Rosiglitazone, a PPARγ ligand, modulates signal transduction pathways during the development of acute TNBS-induced colitis in rats. Eur J Pharmacol 562:247–258

    Article  PubMed  Google Scholar 

  9. Zhang M, Deng C, Zheng J, Xia J, Sheng D (2006) Curcumin inhibits trinitrobenzene sulphonic acid-induced colitis in rats by activation of peroxisome proliferator-activated receptor-γ. Int Immunopharmacol 6:1233–1242

    Article  CAS  PubMed  Google Scholar 

  10. Speca S, Dubuquoy L, Desreumaux P (2014) Peroxisome proliferator-activated receptor γ in the colon: inflammation and innate antimicrobial immunity. J Clin Gastroenterol 48:S23–S27

    Article  CAS  PubMed  Google Scholar 

  11. Zhao M, Qian D, Liu P, Shang EX, Jiang S, Guo J, Su SL, Duan JA, Du L, Tao J (2015) Comparative pharmacokinetics of catalpol and acteoside in normal and chronic kidney disease rats after oral administration of Rehmannia glutinosa extract. Biomed Chromatogr 29:1842–1848

    Article  CAS  PubMed  Google Scholar 

  12. Tong S, Chen L, Zhang Q, Liu J, Yan J, Ito Y (2015) Separation of catalpol from Rehmannia glutinosa Libosch. by high-speed countercurrent chromatography. J Chromatogr Sci 53:725–729

    Article  PubMed  Google Scholar 

  13. Yu MC, Lin SK, Lai JN, Wei JC, Cheng CY (2014) The traditional Chinese medicine prescription patterns of Sjögren’s patients in Taiwan: a population-based study. J Ethnopharmacol 155:435–442

    Article  PubMed  Google Scholar 

  14. Liu CL, Cheng L, Ko CH, Wong CW, Cheng WH, Cheung DW, Leung PC, Fung KP, Bik-San Lau C (2012) Bioassay-guided isolation of anti-inflammatory components from the root of Rehmannia glutinosa and its underlying mechanism via inhibition of iNOS pathway. J Ethnopharmacol 143:867–875

    Article  CAS  PubMed  Google Scholar 

  15. Liu YR, Lei RY, Wang CE, Zhang BA, Lu H, Zhu HC, Zhang GB (2014) Effects of catalpol on ATPase and amino acids in gerbils with cerebral ischemia/reperfusion injury. Neurol Sci 35:1229–1233

    Article  PubMed  Google Scholar 

  16. Zhang X, Liu W, Niu X, An L (2010) Systemic administration of catalpol prevents D-galactose induced mitochondrial dysfunction in mice. Neurosci Lett 473:224–228

    Article  CAS  PubMed  Google Scholar 

  17. Zhang A, Hao S, Bi J, Bao Y, Zhang X, An L, Jiang B (2009) Effects of catalpol on mitochondrial function and working memory in mice after lipopolysaccharide-induced acute systemic inflammation. Exp Toxicol Pathol 61:461–469

    Article  CAS  PubMed  Google Scholar 

  18. Zhang X, Jin C, Li Y, Guan S, Han F, Zhang S (2013) Catalpol improves cholinergic function and reduces inflammatory cytokines in the senescent mice induced by d-galactose. Food Chem Toxicol 58:50–55

    Article  CAS  PubMed  Google Scholar 

  19. Fu K, Piao T, Wang M, Zhang J, Jiang J, Wang X, Liu H (2014) Protective effect of catalpol on lipopolysaccharide-induced acute lung injury in mice. Int Immunopharmacol 23:400–406

    Article  CAS  PubMed  Google Scholar 

  20. Zhou J, Xu G, Ma S, Li F, Yuan M, Xu H, Huang K (2015) Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways. Biochem Biophys Res Commun 467:853–858

    Article  CAS  PubMed  Google Scholar 

  21. Choo J, Lee Y, Yan XJ, Noh TH, Kim SJ, Son S, Pothoulakis C, Moon HR, Jung JH, Im E (2015) A novel peroxisome proliferator-activated receptor (PPAR)-γ agonist 2-hydroxyethyl 5-chloro-4,5-didehydrojasmonate exerts anti-inflammatory effects in colitis. J Biol Chem 290:25609–25619

    Article  CAS  PubMed  Google Scholar 

  22. Celinski K, Dworzanski T, Fornal R, Korolczuk A, Madro A, Slomka M (2012) Comparison of the anti-inflammatory and therapeutic actions of PPAR-γ agonists rosiglitazone and troglitazone in experimental colitis. J Physiol Pharmacol 63:631–640

    CAS  PubMed  Google Scholar 

  23. Moon MR, Parikh AA, Pritts TA, Kane C, Fischer JE, Salzman AL, Hasselgren PO (2000) Interleukin-1β induces complement component C3 and IL-6 production at the basolateral and apical membranes in a human intestinal epithelial cell line. Shock 13:374–378

    Article  CAS  PubMed  Google Scholar 

  24. Parhar K, Ray A, Steinbrecher U, Nelson C, Salh B (2003) The p38 mitogen-activated protein kinase regulates interleukin-1β-induced IL-8 expression via an effect on the IL-8 promoter in intestinal epithelial cells. Immunology 108:502–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hollebeeck S, Raas T, Piront N, Schneider YJ, Toussaint O, Larondelle Y, During A (2011) Dimethyl sulfoxide (DMSO) attenuates the inflammatory response in the in vitro intestinal Caco-2 cell model. Toxicol Lett 206:268–275

    Article  CAS  PubMed  Google Scholar 

  26. Atreya R, Neurath MF (2005) Involvement of IL-6 in the pathogenesis of inflammatory bowel disease and colon cancer. Clin Rev Allergy Immunol 28:187–196

    Article  CAS  PubMed  Google Scholar 

  27. Khan WI, Motomura Y, Wang H, El-Sharkawy RT, Verdu EF, Verma-Gandhu M, Rollins BJ, Collins SM (2006) Critical role of MCP-1 in the pathogenesis of experimental colitis in the context of immune and enterochromaffin cells. Am J Physiol Gastrointest Liver Physiol 291:G803–G811

    Article  CAS  PubMed  Google Scholar 

  28. Imada A, Ina K, Shimada M, Yokoyama T, Yokoyama Y, Nishio Y, Yamaguchi T, Ando T, Kusugami K (2001) Coordinate upregulation of interleukin-8 and growth-related gene product-α is present in the colonic mucosa of inflammatory bowel. Scand J Gastroenterol 36:854–864

    Article  CAS  PubMed  Google Scholar 

  29. Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris TP, Rastinejad F (2008) Structure of the intact PPAR-γ-RXR- nuclear receptor complex on DNA. Nature 456:350–356

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wahli W (2008) A gut feeling of the PXR, PPAR and NF-κB connection. J Intern Med 263:613–619

    Article  CAS  PubMed  Google Scholar 

  31. Takagi T, Naito Y, Tomatsuri N, Handa O, Ichikawa H, Yoshida N, Yoshikawa T (2008) Pioglitazone, a PPAR-γ ligand, provides protection from dextran sulfate sodium-induced colitis in mice in association with inhibition of the NF-κB-cytokine cascade. Redox Rep 7:283–289

    Article  Google Scholar 

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Correspondence to Kyoung Sik Park.

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Park, K.S. Catalpol reduces the production of inflammatory mediators via PPAR-γ activation in human intestinal Caco-2 cells. J Nat Med 70, 620–626 (2016). https://doi.org/10.1007/s11418-016-0988-y

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  • DOI: https://doi.org/10.1007/s11418-016-0988-y

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