[en] Gallic acid is a phenolic compound that exhibits antibacterial, antioxidative and anti-inflammatory functions. In a previous study, we found that dietary supplementation with gallic acid decreased incidence of diarrhoea and protected intestinal integrity in weaning piglets. However, the underlying mechanism remains unclear. Here, a pig intestinal epithelial cell line (IPEC-J2) was used as an in vitro model to explore the antioxidant and anti-inflammatory capacity of gallic acid. IPEC-J2 cells were stimulated with hydrogen peroxide (H2 O2 ) and lipopolysaccharide (LPS) to establish oxidative and inflammatory models, respectively. Results showed that H2 O2 significantly decreased catalase (CAT) secretion and CAT mRNA abundance in the cells (p < 0.05), while pretreatment with gallic acid did not prevent the decrease in CAT expression induced by H2 O2 . However, gallic acid pretreatment mitigated the increased expression of the tumour necrosis factor-α and interleukin-8 genes caused by LPS in IPEC-J2 cells (p < 0.05). In addition, pretreatment with gallic acid significantly suppressed phosphorylation of NF-κB and IκBα in LPS-stimulated IPEC-J2 cells. Moreover, LPS stimulation decreased the protein abundance of zona occludens 1 (ZO-1) and occludin, while pretreatment with gallic acid preserved expression level of tight junction proteins ZO-1 and occludin in LPS-stimulated IPEC-J2 cells (p < 0.05). In conclusion, gallic acid may mitigate LPS-induced inflammatory responses by inhibiting the NF-κB signalling pathway, exerting positive effects on the barrier function of IPEC-J2 cells.
Disciplines :
Agriculture & agronomy
Author, co-author :
Cai, Long ✱; Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, China
Wei, Zixi ✱; Université de Liège - ULiège > TERRA Research Centre ; Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, China
Zhao, Xuemei ; Université de Liège - ULiège > TERRA Research Centre ; Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, China
Li, Yanpin; Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, China
Li, Xilong; Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, China
Jiang, Xianren ; Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, China
✱ These authors have contributed equally to this work.
Language :
English
Title :
Gallic acid mitigates LPS-induced inflammatory response via suppressing NF-κB signalling pathway in IPEC-J2 cells.
This work was financially supported by the National Key Research and Development Program of China (2018YFD0500600), the Beijing Natural Science Foundation (6174049), and the Elite Youth Program of Chinese Academy of Agricultural Sciences (to X.L. Li).
Abarikwu, S. (2014). Kolaviron, a natural flavonoid from the seeds of Garcinia kola, reduces LPS-induced inflammation in macrophages by combined inhibition of IL-6 secretion, and inflammatory transcription factors, ERK1/2, NF-κB, p38, Akt, p-c-JUN and JNK. Biochimica Et Biophysica Acta-General Subjects, 1840(7), 2373–2381. https://doi.org/10.1016/j.bbagen.2014.03.006
Bravo, L. (1998). Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutrition Reviews, 56(11), 317–333. https://doi.org/10.1111/j.1753-4887.1998.tb01670.x
Cai, L., Li, Y., Wei, Z., Li, X., & Jiang, X. (2020). Effects of dietary gallic acid on growth performance, diarrhea incidence, intestinal morphology, plasma antioxidant indices, and immune response in weaned piglets. Animal Feed Science and Technology, 261, 114391. https://doi.org/10.1016/j.anifeedsci.2020.114391
Cao, S., Wang, C., Yan, J., Li, X., Wen, J., & Hu, C. (2020). Curcumin ameliorates oxidative stress-induced intestinal barrier injury and mitochondrial damage by promoting Parkin dependent mitophagy through AMPK-TFEB signal pathway. Free Radical Biology and Medicine, 14, 8–22. https://doi.org/10.1016/j.freeradbiomed.2019.12.004
Chen, M., Liu, Y., Xiong, S., Wu, M., Li, B., Ruan, Z., & Hu, X. (2019). Dietary L-tryptophan alleviated LPS-induced intestinal barrier injury by regulating tight junctions in a Caco-2 cell monolayer model. Food & Function, 10, 2390–2398. https://doi.org/10.1039/C9FO00123A
Han, F., Zhang, H., Xia, X., Xiong, H., Song, D., Zong, X., & Wang, Y. (2015). Porcine β-defensin 2 attenuates inflammation and mucosal lesions in dextran sodium sulfate-induced colitis. Journal of Immunology, 194(4), 1882–1893. https://doi.org/10.4049/jimmunol.1402300
He, C., Deng, J., Hu, X., Zhou, S., Wu, J., Xiao, D. I., Darko, K. O., Huang, Y., Tao, T., Peng, M., Wang, Z., & Yang, X. (2019). Vitamin A inhibits the action of LPS on the intestinal epithelial barrier function and tight junction proteins. Food & Function, 10, 1235–1242. https://doi.org/10.1039/C8FO01123K
Hsiang, C., Hseu, Y., Chang, Y., Senthil Kumar, K., Ho, T., & Yang, H. (2013). Toona sinensis and its major bioactive compound gallic acid inhibit LPS-induced inflammation in nuclear factor-κB transgenic mice as evaluated by in vivo bioluminescence imaging. Food Chemistry, 136(2), 426–434. https://doi.org/10.1016/j.foodchem.2012.08.009
Hu, B., Zhang, H., Meng, X., Wang, F., & Wang, P. (2014). Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264. 7 macrophages. Journal of Ethnopharmacology, 153, 846–853. https://doi.org/10.1016/j.jep.2014.03.059
Jantan, I., Ilangkovan, M., Yuandani, M., & Mohamad, H. F. (2014). Correlation between the major components of phyllanthus amarus and phyllanthus urinaria and their inhibitory effects on phagocytic activity of human neutrophils. BMC Complementary and Alternative Medicine, 14, 429. https://doi.org/10.1186/1472-6882-14-429
Kanda, H., Tateya, S., Tamori, Y., Kotani, K., Hiasa, K., Kitazawa, R., & Kasuga, M. (2006). MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. Journal of Clinical Investigation, 116(6), 1494–1505. https://doi.org/10.1172/JCI26498
Kim, S. H., Jun, C. D., Suk, K., Choi, B. J., Lim, H., Park, S., Lee, S. H., Shin, H. Y., Kim, D. K., & Shin, T. Y. (2006). Gallic acid inhibits histamine release and proinflammatory cytokine production in mast cells. Toxicological Sciences, 91(1), 123–131. https://doi.org/10.1093/toxsci/kfj063
Kroes, B. H., Van den Berg, A. J. J., Quarles van Ufford, H. C., Van Dijk, H., & Labadie, R. P. (1992). Anti-inflammatory activity of gallic acid. Planta Medica, 58(6), 499–504. https://doi.org/10.1055/s-2006-961535
Kundu, J., Shin, Y., & Surh, Y. (2006). Resveratrol modulates phorbol ester-induced proinflammatory signal transduction pathways in mouse skin in vivo: NF-κB and AP-1 as prime targets. Biochemical Pharmacology, 72(11), 1506–1515. https://doi.org/10.1016/j.bcp.2006.08.005
Liu, B., Jiang, X., Cai, L., Zhao, X., Dai, Z., Wu, G., & Li, X. (2019). Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets. Journal of Animal Science and Biotechnology, 10, 69. https://doi.org/10.1186/s40104-019-0379-9
Liu, S., Li, S., Lin, G., Markkinen, N., Yang, H., Zhu, B., & Zhang, B. (2019). Anthocyanin copigmentation and color attributes of bog bilberry syrup wine during bottle aging: Effect of tannic acid and gallic acid extracted from Chinese gallnut. Journal of Food Processing and Preservation, 43, e14041. https://doi.org/10.1111/jfpp.14041
Lu, R., Yang, W., & Hu, Y. (2014). The role of epithelial tight junctions involved in pathogen infections. Molecular Biology Reports, 41(10), 6591–6610. https://doi.org/10.1007/s11033-014-3543-5.
Mennigen, R., Nolte, K., Rijcken, E., Utech, M., Löffler, B., Senninger, N., & Bruewer, M. (2009). Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 296, G1140–G1149. https://doi.org/10.1152/ajpgi.90534.2008
Odenwald, M., & Turner, J. (2017). The intestinal epithelial barrier: A therapeutic target? Nature Reviews Gastroenterology & Hepatology, 14(1), 9–21. https://doi.org/10.1038/nrgastro.2016.169
Phonsatta, N., Deetae, P., Luangpituksa, P., Grajeda-Iglesias, C., Figueroa-Espinoza, M. C., Le Comte, J., Villeneuve, P., Decker, E. A., Visessanguan, W., & Panya, A. (2017). Comparison of antioxidant evaluation assays for investigating antioxidative activity of gallic acid and its alkyl esters in different food matrices. Journal of Agricultural and Food Chemistry, 65(34), 7509–7518. https://doi.org/10.1021/acs.jafc.7b02503
Pitman, R., & Blumberg, R. (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. https://doi.org/10.1007/s005350070017
Samuel, K., Wang, J., Yue, H., Wu, S., Zhang, H., Duan, Z., & Qi, G. (2017). Effects of dietary gallic acid supplementation on performance, antioxidant status, and jejunum intestinal morphology in broiler chicks. Poultry Science, 96(8), 2768–2775. https://doi.org/10.3382/ps/pex091
Schulzke, J. D., Ploeger, S., Amasheh, M., Fromm, A., Zeissig, S., Troeger, H., Richter, J., Bojarski, C., Schumann, M., & Fromm, M. (2009). Epithelial tight junctions in intestinal inflammation. Annals of the New York Academy of Sciences, 1165, 294–300. https://doi.org/10.1111/j.1749-6632.2009.04062.x
Shao, D., Li, J., Li, J., Tang, R., Liu, L., Shi, J., & Yang, H. (2015). Inhibition of gallic acid on the growth and biofilm formation of escherichia coli and streptococcus mutans. Journal of Food Science, 80(6), 1299–1305. https://doi.org/10.1111/1750-3841.12902
Suzuki, T. (2013). Regulation of intestinal epithelial permeability by tight junctions. Cellular and Molecular Life Sciences, 70(4), 631–659. https://doi.org/10.1007/s00018-012-1070-x
Suzuki, T., Yoshinaga, N., & Tanabe, S. (2011). Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium. Journal of Biological Chemistry, 286(36), 31263–31271. https://doi.org/10.1074/jbc.M111.238147
Tanaka, M., Kishimoto, Y., Sasaki, M., Sato, A., Kamiya, T., Kondo, K., & Iida, K. (2018). Terminalia bellirica (Gaertn.) Roxb. extract and gallic acid attenuate LPS-Induced inflammation and oxidative stress via MAPK/NF-κB and Akt/AMPK/Nrf2 pathways. Oxidative Medicine and Cellular Longevity, 2018, 9364364. https://doi.org/10.1155/2018/9364364
Uwe, S. (2008). Anti-inflammatory interventions of NF-κB signaling: Potential applications and risks. Biochemical Pharmacology, 75(8), 1567–1579. https://doi.org/10.1016/j.bcp.2007.10.027
Vergauwen, H., Prims, S., Degroote, J., Wang, W., Casteleyn, C., van Cruchten, S., de Smet, S., Michiels, J., & van Ginneken, C. (2016). In Vitro Investigation of six antioxidants for pig diets. Antioxidants, 5(4), 41. https://doi.org/10.3390/antiox5040041
Wang, H., Zhang, C., Wu, G., Sun, Y., Wang, B., He, B., Dai, Z., & Wu, Z. (2015). Glutamine enhances tight junction protein expression and modulates corticotropin-releasing factor signaling in the jejunum of weanling piglets. Journal of Nutrition, 145(1), 25–31. https://doi.org/10.3945/jn.114.202515
Wei, C., Yang, K., Zhao, G., Lin, S., & Xu, Z. (2016). Effect of dietary supplementation of gallic acid on nitrogen balance, nitrogen excretion pattern and urinary nitrogenous constituents in beef cattle. Archives of Animal Nutrition, 70(5), 416–423. https://doi.org/10.1080/1745039X.2016.1214345
Yang, F., Oz, H., Barve, S., De Villiers, W. J., McClain, C., & Varilek, G. W. (2001). The green tea polyphenol (−)-epigallocatechin-3-gallate blocks nuclear factor-κB activation by inhibiting IκB kinase activity in the intestinal epithelial cell line IEC-6. Molecular Pharmacology, 60(3), 528–533.
Yen, G., Duh, P., & Tsai, H. (2002). Antioxidant and pro-oxidant properties of ascorbic acid and gallic acid. Food Chemistry, 79(3), 307–313. https://doi.org/10.1016/S0308-8146(02)00145-0
Yoon, W. J., Moon, J. Y., Song, G., Lee, Y. K., Han, M. S., Lee, J. S., Ihm, B. S., Lee, W. J., Lee, N. H., & Hyun, C. G. (2010). Artemisia fukudo essential oil attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in RAW 264.7 macrophages. Food and Chemical Toxicology, 48(5), 1222–1229. https://doi.org/10.1016/j.fct.2010.02.014
