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Paeoniflorin Prevents Intestinal Barrier Disruption and Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in Caco-2 Cell Monolayers

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Abstract

Inflammatory bowel disease (IBD) in humans is closely related to bacterial infection and the disruption of the intestinal barrier. Paeoniflorin (PF), a bioactive compound from Paeonia lactiflora Pallas plants, exerts a potential effect of anti-inflammatory reported in various researches. However, the effect of PF on intestinal barrier function and its related mechanisms has not been identified. Here, we investigate the PF potential anti-inflammatory effect on lipopolysaccharide (LPS)-stimulated human Caco-2 cell monolayers and explore its underlying key molecular mechanism. In this context, PF significantly increased TEER value, decreased intestinal epithelium FITC-dextran flux permeability, and restored the expressions of occludin, ZO-1, and claudin5 in LPS-induced Caco-2 cell. In vitro, treatment of PF significantly inhibited LPS-induced expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9). In addition, we found that PF suppressed nuclear factor kappa B (NF-κB) signaling via activating the Nrf2/HO-1 signaling pathways in ILPS-stimulated Caco-2 cells. Our findings indicate that PF has an inhibitory effect on endothelial injury. Our findings suggested that PF has an anti-inflammatory effect in ILPS-stimulated Caco-2 cells, which might be a potential therapeutic agent against IBD and intestinal inflammation.

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References

  1. Bazzoni, Gianfranco, and Elisabetta Dejana. 2004. Endothelial cell-to-cell junctions: Molecular organization and role in vascular homeostasis. Physiological Reviews 84 (3): 869–901.

    Article  CAS  Google Scholar 

  2. Chang, K.W., and C.Y. Kuo. 2015. 6-Gingerol modulates proinflammatory responses in dextran sodium sulfate (DSS)-treated Caco-2 cells and experimental colitis in mice through adenosine monophosphate-activated protein kinase (AMPK) activation. Food & Function 6 (10): 3334–3341. https://doi.org/10.1039/c5fo00513b.

    Article  CAS  Google Scholar 

  3. Chen, Qianru, Oliver Chen, Isabela M. Martins, Hou Hu, Zhao Xue, Jeffrey B. Blumberg, and Bafang Li. 2017. Collagen peptides ameliorate intestinal epithelial barrier dysfunction in immunostimulatory Caco-2 cell monolayers via enhancing tight junctions. Food & Function 8 (3): 1144–1151. https://doi.org/10.1039/c6fo01347c.

    Article  CAS  Google Scholar 

  4. Chen, J., M. Zhang, M. Zhu, J. Gu, J. Song, L. Cui, D. Liu, Q. Ning, X. Jia, and L. Feng. 2018. Paeoniflorin prevents endoplasmic reticulum stress-associated inflammation in lipopolysaccharide-stimulated human umbilical vein endothelial cells via the IRE1alpha/NF-kappaB signaling pathway. Food & Function 9 (4): 2386–2397. https://doi.org/10.1039/c7fo01406f.

    Article  CAS  Google Scholar 

  5. Cocetta, V., D. Catanzaro, V. Borgonetti, E. Ragazzi, M.C. Giron, P. Governa, I. Carnevali, M. Biagi, and M. Montopoli. 2019. A fixed combination of probiotics and herbal extracts attenuates intestinal barrier dysfunction from inflammatory stress in an in vitro model using Caco-2 cells. Recent Patents on Food, Nutrition & Agriculture 10 (1): 62–69. https://doi.org/10.2174/2212798410666180808121328.

    Article  CAS  Google Scholar 

  6. Governa, P., M. Marchi, V. Cocetta, B. De Leo, P.T.K. Saunders, D. Catanzaro, E. Miraldi, M. Montopoli, and M. Biagi. 2018. Effects of Boswellia Serrata Roxb. and Curcuma longa L. in an in vitro intestinal inflammation model using immune cells and Caco-2. Pharmaceuticals (Basel) 11 (4). https://doi.org/10.3390/ph11040126.

    Article  CAS  Google Scholar 

  7. Guan, Qingdong, and Jiguo Zhang. 2017. Recent advances: The imbalance of cytokines in the pathogenesis of inflammatory bowel disease. Mediators of Inflammation 2017: 1–8.

    Google Scholar 

  8. Guo, Ruo-Bing, Guo-Feng Wang, An-Peng Zhao, Gu Jun, Xiu-Lan Sun, and Hu. Gang. 2012. Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses. PLoS One 7 (11): e49701.

    Article  CAS  Google Scholar 

  9. He, C., J. Deng, X. Hu, S. Zhou, J. Wu, D. Xiao, K.O. Darko, Y. Huang, T. Tao, M. Peng, Z. Wang, and X. Yang. 2019. Vitamin A inhibits the action of LPS on the intestinal epithelial barrier function and tight junction proteins. Food & Function 10 (2): 1235–1242. https://doi.org/10.1039/c8fo01123k.

    Article  CAS  Google Scholar 

  10. He, Caimei, Jun Deng, Xin Hu, Sichun Zhou, Jingtao Wu, Di Xiao, Kwame Oteng Darko, Yanjun Huang, Ting Tao, and Mei Peng. 2019. Vitamin A inhibits the action of LPS on the intestinal epithelial barrier function and tight junction proteins. Food & Function 10 (2): 1235–1242.

    Article  CAS  Google Scholar 

  11. Heller, Frank, Peter Florian, Christian Bojarski, Jan Richter, Melanie Christ, Bernd Hillenbrand, Joachim Mankertz, Alfred H. Gitter, Nataly Bürgel, and Michael Fromm. 2005. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129 (2): 550–564.

    Article  CAS  Google Scholar 

  12. Jiang, Zequn, Weiping Chen, Xiaojing Yan, Lei Bi, Sheng Guo, and Zhen Zhan. 2014. Paeoniflorin protects cells from GalN/TNF-α-induced apoptosis via ER stress and mitochondria-dependent pathways in human L02 hepatocytes. Acta Biochimica et Biophysica Sinica 46 (5): 357–367.

    Article  Google Scholar 

  13. Kim, Y.J., and W. Park. 2016. Anti-inflammatory effect of quercetin on RAW 264.7 mouse macrophages induced with polyinosinic-polycytidylic acid. Molecules 21 (4): 450. https://doi.org/10.3390/molecules21040450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lee, J.M., J. Li, D.A. Johnson, T.D. Stein, A.D. Kraft, M.J. Calkins, R.J. Jakel, and J.A. Johnson. 2005. Nrf2, a multi-organ protector? The FASEB Journal 19 (9): 1061–1066. https://doi.org/10.1096/fj.04-2591hyp.

    Article  CAS  PubMed  Google Scholar 

  15. Lee, D.F., H.P. Kuo, M. Liu, C.K. Chou, W. Xia, Y. Du, J. Shen, et al. 2009. KEAP1 E3 ligase-mediated downregulation of NF-kappaB signaling by targeting IKKbeta. Molecular Cell 36 (1): 131–140. https://doi.org/10.1016/j.molcel.2009.07.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lee, Seung Hoon, Jeong eun Kwon, and Mi-La Cho. 2018. Immunological pathogenesis of inflammatory bowel disease. Intestinal Research 16 (1): 26–42.

    Article  Google Scholar 

  17. Liu, G.H., J. Qu, and X. Shen. 2008. NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK. Biochimica et Biophysica Acta 1783 (5): 713–727. https://doi.org/10.1016/j.bbamcr.2008.01.002.

    Article  CAS  PubMed  Google Scholar 

  18. Malik, Talha A. 2015. Inflammatory bowel disease: Historical perspective, epidemiology, and risk factors. Surgical Clinics 95 (6): 1105–1122.

    PubMed  Google Scholar 

  19. Nam, Kyong-Nyon, Che Gyem Yae, Joung-Woo Hong, Dong-Hyung Cho, Joon H. Lee, and Eunjoo H. Lee. 2013. Paeoniflorin, a monoterpene glycoside, attenuates lipopolysaccharide-induced neuronal injury and brain microglial inflammatory response. Biotechnology Letters 35 (8): 1183–1189.

    Article  CAS  Google Scholar 

  20. Nunes, Carla, Leonor Almeida, Rui M. Barbosa, and João Laranjinha. 2017. Luteolin suppresses the JAK/STAT pathway in a cellular model of intestinal inflammation. Food & Function 8 (1): 387–396. https://doi.org/10.1039/c6fo01529h.

    Article  CAS  Google Scholar 

  21. Nunes, C., V. Freitas, L. Almeida, and J. Laranjinha. 2019. Red wine extract preserves tight junctions in intestinal epithelial cells under inflammatory conditions: Implications for intestinal inflammation. Food & Function 10 (3): 1364–1374. https://doi.org/10.1039/c8fo02469c.

    Article  CAS  Google Scholar 

  22. Omonijo, F.A., S. Liu, Q. Hui, H. Zhang, L. Lahaye, J.C. Bodin, J. Gong, M. Nyachoti, and C. Yang. 2019. Thymol improves barrier function and attenuates inflammatory responses in porcine intestinal epithelial cells during lipopolysaccharide (LPS)-induced inflammation. Journal of Agricultural and Food Chemistry 67 (2): 615–624. https://doi.org/10.1021/acs.jafc.8b05480.

    Article  CAS  PubMed  Google Scholar 

  23. Pitman, Richard S., and Richard S. Blumberg. 2000. First line of defense: The role of the intestinal epithelium as an active component of the mucosal immune system. Journal of Gastroenterology 35 (11): 805–814.

    Article  CAS  Google Scholar 

  24. Sartor, R. Balfour. 2006. Mechanisms of disease: Pathogenesis of Crohn’s disease and ulcerative colitis. Nature Reviews Gastroenterology & Hepatology 3 (7): 390.

    CAS  Google Scholar 

  25. Siliciano, J.D., and Daniel A. Goodenough. 1988. Localization of the tight junction protein, ZO-1, is modulated by extracellular calcium and cell-cell contact in Madin-Darby canine kidney epithelial cells. The Journal of Cell Biology 107 (6): 2389–2399.

    Article  CAS  Google Scholar 

  26. Tang, X., B. Liu, X. Wang, Q. Yu, and R. Fang. 2018. Epidermal growth factor, through alleviating oxidative stress, protect IPEC-J2 cells from lipopolysaccharides-induced apoptosis. International Journal of Molecular Sciences 19 (3). https://doi.org/10.3390/ijms19030848.

    Article  Google Scholar 

  27. Tenhunen, R., H.S. Marver, and R. Schmid. 1968. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proceedings of the National Academy of Sciences of the United States of America 61 (2): 748–755.

    Article  CAS  Google Scholar 

  28. Tsukita, Shoichiro, Mikio Furuse, and Masahiko Itoh. 2001. Multifunctional strands in tight junctions. Nature Reviews Molecular Cell Biology 2 (4): 285–293.

    Article  CAS  Google Scholar 

  29. Wu, Y.-M., R. Jin, L. Yang, J. Zhang, Q. Yang, Y.-Y. Guo, X.-B. Li, S.-B. Liu, X.-X. Luo, and M.-G. Zhao. 2013. Phosphatidylinositol 3 kinase/protein kinase B is responsible for the protection of paeoniflorin upon H2O2-induced neural progenitor cell injury. Neuroscience 240: 54–62.

    Article  CAS  Google Scholar 

  30. Xu, Huan, Jie Song, Xinghua Gao, Zhao Xu, Xianxiang Xu, Yufeng Xia, and Yue Dai. 2013. Paeoniflorin attenuates lipopolysaccharide-induced permeability of endothelial cells: Involvements of F-actin expression and phosphorylations of PI3K/Akt and PKC. Inflammation 36 (1): 216–225.

    Article  CAS  Google Scholar 

  31. Yin, Dou, Yuan-Yuan Liu, Tian-Xiao Wang, Zhen-Zhen Hu, Qu Wei-Min, Jiang-Fan Chen, Neng-Neng Cheng, and Zhi-Li Huang. 2016. Paeoniflorin exerts analgesic and hypnotic effects via adenosine A 1 receptors in a mouse neuropathic pain model. Psychopharmacology 233 (2): 281–293.

    Article  CAS  Google Scholar 

  32. Zeissig, Sebastian, Nataly Bürgel, Dorothee Günzel, Jan Richter, Joachim Mankertz, Ulrich Wahnschaffe, Anton Josef Kroesen, Martin Zeitz, Michael Fromm, and Joerg Dieter Schulzke. 2007. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut 56 (1): 61–72.

    Article  CAS  Google Scholar 

  33. Zhang, Bingkun, and Yuming Guo. 2009. Supplemental zinc reduced intestinal permeability by enhancing occludin and zonula occludens protein-1 (ZO-1) expression in weaning piglets. British Journal of Nutrition 102 (5): 687–693.

    Article  CAS  Google Scholar 

  34. Zhou, J., L. Wang, J. Wang, C. Wang, Z. Yang, C. Wang, Y. Zhu, and J. Zhang. 2016. Paeoniflorin and albiflorin attenuate neuropathic pain via MAPK pathway in chronic constriction injury rats. Evidence-based Complementary and Alternative Medicine 2016: 8082753–8082711. https://doi.org/10.1155/2016/8082753.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was financially supported by Grants from National Natural Science Foundation of China (81570495).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Xi-Xi Wu, Ru-Ru Chen, Tang Li, Hua-Jun Ye, Wei Xie & Zhi-Ming Huang

  2. Department of Gastroenterology Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Xie-Lin Huang

  3. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Zhi-Ming Huang & Gao-Zhong Cao

  4. Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Gao-Zhong Cao

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  1. Xi-Xi Wu
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Wu, XX., Huang, XL., Chen, RR. et al. Paeoniflorin Prevents Intestinal Barrier Disruption and Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in Caco-2 Cell Monolayers. Inflammation 42, 2215–2225 (2019). https://doi.org/10.1007/s10753-019-01085-z

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