Paeoniflorin Prevents Intestinal Barrier Disruption and Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in Caco-2 Cell Monolayers
- 297 Downloads
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.
KEY WORDSpaeoniflorin intestinal barrier tight junction protein Nrf2/OH-1 NF-κB
This work was financially supported by Grants from National Natural Science Foundation of China (81570495).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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
- 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle Scholar
- 24.Sartor, R. Balfour. 2006. Mechanisms of disease: Pathogenesis of Crohn’s disease and ulcerative colitis. Nature Reviews Gastroenterology & Hepatology 3 (7): 390.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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefPubMedPubMedCentralGoogle Scholar