Science China Life Sciences

, Volume 62, Issue 8, pp 1019–1027 | Cite as

Macleaya cordata extract alleviated oxidative stress and altered innate immune response in mice challenged with enterotoxigenic Escherichia coli

  • Guiping Guan
  • Sujuan Ding
  • Yulong Yin
  • Veeramuthu Duraipandiyan
  • Naif Abdullah Al-Dhabi
  • Gang LiuEmail author
Research Paper


This study examines the effects of dietary Macleaya cordata extract (MCE) on bacterial burden and resistance to enterotoxigenic Escherichia coli (ETEC) in ICR mice. ICR mice were randomly distributed into one of the following groups: (i) basal diet; (ii) basal diet with 200 mg kg−1 MCE; (iii) basal diet challenged with ETEC; and (iv) basal diet with 200 mg kg−1 MCE and challenged with ETEC. Following a 7-day period of pre-treatment, CTRL-ETEC and MCE-ETEC mice were subjected to oral infection using 5×108E. coli SEC 470. The results showed dietary 200 mg kg−1 MCE markedly reduced intestinal ETEC burden (P < 0.05) and the disease-associated mortality was significantly alleviated in the MCE treated group (P < 0.05). In addition, dietary MCE markedly alleviated ETEC-induced oxidative stress, evidenced by the lowered methane dicarboxylic aldehyde (MDA) abundance and enhanced activities of catalase and glutathione peroxidase (P < 0.05). Furthermore, MCE mice exhibited higher immune activity, which might have further mediated ETEC infection. These results indicate MCE plays a preventative role with respect to ETEC infection. Future research should aim to develop MCE as a therapeutic approach to the promotion of intestinal health and a safeguard against ETEC infection.

Macleaya cordata extract enterotoxigenic Escherichia coli bacterial burden oxidative stress 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



This research was supported by the National Natural Science Foundation of China (31772642, 31402092), the China Scholarship Council (201708430008), Scientific Research Fund of Hunan Provincial Education Department (17K043), Hunan Provincial Science and Technology Department (2017NK2322, 2018TP2031), China Postdoctoral Science Foundation (2018M632963), Double First-class Construction Project of Hunan Agricultural University (SYL201802002). The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this research through the Research Group Project No. RGP-213.


  1. Bergstrom, K.S.B., Kissoon-Singh, V., Gibson, D.L., Ma, C.X., Montero, M., Sham, H.P., Ryz, N., Huang, T.N., Velcich, A., Finlay, B.B., et al. (2010). Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa. PLoS Path 2010, 6.Google Scholar
  2. Bevins, C.L., and Salzman, N.H. (2011). Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Micro 9, 35–368.CrossRefGoogle Scholar
  3. Casewell, M., Friis, C., Marco, E., McMullin, P., and Phillips, I. (2003). The European ban on growth-promoting antibiotics and emerging consequences for human and animal health. J Antimicrobial Chemother 52, 159–161.CrossRefGoogle Scholar
  4. Chirino, Y.I., and Pedraza-Chaverri, J. (2009). Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicologic Pathol 61, 223–242.CrossRefGoogle Scholar
  5. Dvorák, Z., Sovadinová, I., Bláha, L., Giesy, J.P., and Ulrichová, J. (2006). Quaternary benzo[c]phenathridine alkaloids sanguinarine and chelerythrine do not affect transcriptional activity of aryl hydrocarbon receptor: Analyses in rat hepatoma cell line h4iie.Luc. Food Chem Toxicol 44, 1466–1473.CrossRefPubMedGoogle Scholar
  6. Fairbrother, J.M., Nadeau, É., and Gyles, C.L. (2005). Escherichia coli in postweaning diarrhea in pigs: An update on bacterial types, pathogenesis, and prevention strategies. Anim Health Res Rev 6, 17–39.CrossRefPubMedGoogle Scholar
  7. Fleckenstein, J.M., Hardwidge, P.R., Munson, G.P., Rasko, D.A., Sommerfelt, H., and Steinsland, H. (2010). Molecular mechanisms of enterotoxigenic Escherichia coli infection. Microb Infect 12, 89–98.CrossRefGoogle Scholar
  8. Gao, R., Li, Y., Lin, J., Tan, C., and Feng, Y. (2016). Unexpected complexity of multidrug resistance in the mcr-1-harbouring Escherichia coli. Sci China Life Sci 59, 732–734.CrossRefPubMedGoogle Scholar
  9. Jang, M.K., Kim, S.H., Lee, K.Y., Kim, T.B., Moon, K.A., Park, C.S., Bae, Y.J., Zhu, Z., Moon, H.B., and Cho, Y.S. (2010). The tyrosine phosphatase, SHP-1, is involved in bronchial mucin production during oxidative stress. Biochem Biophys Res Commun 393, 137–143.CrossRefPubMedGoogle Scholar
  10. Jia, Z., Zhu, H., Li, J., Wang, X., Misra, H., and Li, Y. (2012). Oxidative stress in spinal cord injury and antioxidant-based intervention. Spinal Cord 50, 264–274.CrossRefPubMedGoogle Scholar
  11. Kuo, C.T., Liu, T. H., Hsu, T.H., Lin, F.Y., and Chen, H. Y. (2016). Protection of Chinese olive fruit extract and its fractions against advanced glycation endproduct-induced oxidative stress and pro-inflammatory factors in cultured vascular endothelial and human monocytic cells. J Funct Foods 27, 526–536.CrossRefGoogle Scholar
  12. Li, N., and Neu, J. (2009). Glutamine deprivation alters intestinal tight junctions via a PI3-K/Akt mediated pathway in Caco-2 cells. J Nutrit 139, 710–714.PubMedGoogle Scholar
  13. Liu, G., Aguilar, Y.M., Zhang, L., Ren, W., Chen, S., Guan, G., Xiong, X., Liao, P., Li, T., Huang, R., et al. (2016). Dietary supplementation with sanguinarine enhances serum metabolites and antibodies in growing pigs. J Anim Sci 94, 75–78.CrossRefGoogle Scholar
  14. Liu, G., Ren, W., Fang, J., Hu, C.A.A., Guan, G., Al-Dhabi, N.A., Yin, J., Duraipandiyan, V., Chen, S., Peng, Y., et al. (2017). L-glutamine and l-arginine protect against enterotoxigenic Escherichia coli infection via intestinal innate immunity in mice. Amino Acids 49, 1945–1954.CrossRefPubMedGoogle Scholar
  15. Ni, H., Martínez, Y., Guan, G., Rodríguez, R., Más, D., Peng, H., Valdivié Navarro, M., and Liu, G. (2016). Analysis of the impact of isoquinoline alkaloids, derived from Macleaya cordata extract, on the development and innate immune response in swine and poultry. Biomed Res Int 2016 (4), 1–7.Google Scholar
  16. Ren, C., Zhao, D., and Zhu, L. (2016). Use of N, O-carboxymethyl chitosan to prevent postsurgical adhesions in a rabbit double uterine horn model: A randomized controlled design. Sci China Life Sci 59, 504–509.CrossRefPubMedGoogle Scholar
  17. Ren, W., Wang, K., Yin, J., Chen, S., Liu, G., Tan, B., Wu, G., Bazer, F.W., Peng, Y., and Yin, Y. (2016). Glutamine-induced secretion of intestinal secretory immunoglobulin A: A mechanistic perspective. Front Immunol 7, 685.CrossRefPubMedGoogle Scholar
  18. Ren, W., Yin, J., Xiao, H., Chen, S., Liu, G., Tan, B., Li, N., Peng, Y., Li, T., Zeng, B., et al. (2017). Intestinal microbiota-derived GABA mediates interleukin-17 expression during enterotoxigenic Escherichia coli infection. Front Immunol 7, 685.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Tang, Z., Yin, Y., Zhang, Y., Huang, R., Sun, Z., Li, T., Chu, W., Kong, X., Li, L., Geng, M., and Tu, Q. (2009). Effects of dietary supplementation with an expressed fusion peptide bovine lactoferricin-lactoferrampin on performance, immune function and intestinal mucosal morphology in piglets weaned at age 21 d. Brit J Nutrit 101, 998–1005.CrossRefPubMedGoogle Scholar
  20. Tourret, J., Willing, B.P., Croxen, M.A., Dufour, N., Dion, S., Wachtel, S., Denamur, E., and Finlay, B.B. (2016). Small intestine early innate immunity response during intestinal colonization by Escherichia coli depends on its extra-intestinal virulence status. PLoS ONE 2016, 11.Google Scholar
  21. van der Fels-Klerx, H.J., Puister-Jansen, L.F., van Asselt, E.D., and Burgers, S.L.G.E. (2011). Farm factors associated with the use of antibiotics in pig production. J Anim Sci 89, 1922–1929.CrossRefPubMedGoogle Scholar
  22. Vandenbroucke, R.E., Vanlaere, I., Van Hauwermeiren, F., Van Wonterghem, E., Wilson, C., and Libert, C. (2014). Pro-inflammatory effects of matrix metalloproteinase 7 in acute inflammation. Mucosal Immunol 7, 579–588.CrossRefPubMedGoogle Scholar
  23. Vereecke, L., Beyaert, R., and van Loo, G. (2011). Enterocyte death and intestinal barrier maintenance in homeostasis and disease. Trends Mol Med 17, 584–593.CrossRefPubMedGoogle Scholar
  24. Vieira, S.L., Oyarzabal, O.A., Freitas, D.M., Berres, J., Pena, J.E.M., Torres, C.A., and Coneglian, J.L.B. (2008). Performance of broilers fed diets supplemented with sanguinarine-like alkaloids and organic acids. J Appl Poultry Res 17, 128–133.CrossRefGoogle Scholar
  25. Xiao, D., Ren, W., Bin, P., Chen, S., Yin, J., Gao, W., Liu, G., Nan, Z., Hu, X., and He, J. (2016). Chitosan lowers body weight through intestinal microbiota and reduces IL-17 expression via mTOR signalling. J Funct Foods 22, 166–176.CrossRefGoogle Scholar
  26. Yin, F.G., Liu, Y.L., Yin, Y.L., Kong, X.F., Huang, R.L., Li, T.J., Wu, G.Y., and Hou, Y. (2009). Dietary supplementation with Astragalus polysaccharide enhances ileal digestibilities and serum concentrations of amino acids in early weaned piglets. Amino Acids 37, 263–270.CrossRefPubMedGoogle Scholar
  27. Yin, J., Duan, J., Cui, Z., Ren, W., Li, T., and Yin, Y. (2015). Hydrogen peroxide-induced oxidative stress activates NF-κB and Nrf2/Keap1 signals and triggers autophagy in piglets. RSC Adv 5, 15479–15486.CrossRefGoogle Scholar
  28. Yin, J., Ren, W., Duan, J., Wu, L., Chen, S., Li, T., Yin, Y., and Wu, G. (2014). Dietary arginine supplementation enhances intestinal expression of SLC7A7 and SLC7A1 and ameliorates growth depression in mycotoxin-challenged pigs. Amino Acids 46, 883–892.CrossRefPubMedGoogle Scholar
  29. Yin, J., Wu, M.M., Xiao, H., Ren, W.K., Duan, J.L., Yang, G., Li, T.J., and Yin, Y.L. (2014). Development of an antioxidant system after early weaning in piglets. J Anim Sci 92, 612–619.CrossRefPubMedGoogle Scholar
  30. Zhang, F., Chen, B., Xiao, S., and Yao, S. (2005). Optimization and comparison of different extraction techniques for sanguinarine and chelerythrine in fruits of Macleaya cordata (Willd) R. Br. Separ Purif Tech 42, 283–290.CrossRefGoogle Scholar
  31. Zhang, Y., and Liang, C. (2016). Innate recognition of microbial-derived signals in immunity and inflammation. Sci China Life Sci 59, 1210–1217.CrossRefPubMedGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Guiping Guan
    • 1
  • Sujuan Ding
    • 1
  • Yulong Yin
    • 2
    • 3
  • Veeramuthu Duraipandiyan
    • 4
  • Naif Abdullah Al-Dhabi
    • 4
  • Gang Liu
    • 1
    • 3
    Email author
  1. 1.College of Bioscience and BiotechnologyHunan Agricultural UniversityChangshaChina
  2. 2.College of Animal ScienceSouth China Agricultural UniversityGuangzhouChina
  3. 3.Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical AgricultureChinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionChangshaChina
  4. 4.Department of Botany and Microbiology, College of ScienceKing Saud UniversityRiyadhSaudi Arabia

Personalised recommendations