Skip to main content
SpringerLink
Log in

Synergistic Effect of Quercetin in Combination with Sulfamethoxazole as New Antibacterial Agent: In Vitro and In Vivo Study

  • Published:
Pharmaceutical Chemistry Journal Aims and scope

The present study was aimed at creating a combination between lower dose of sulfamethoxazole (S) as a broad-spectrum synthetic antibiotic and quercetin (Q), a natural polyphenol to decrease the antibiotic side effects and increase its antioxidant activity. Staphylococcus aureus infected animal model was studied both in vitro and in vivo in comparison to doxycycline (Dox) as standard antibiotic. The in vitro test results indicated that Q exhibited activity alone and in combination with S against tested bacterial strains, while S in low concentration was inactive. The in vivo results revealed that the S+Q combination in mice showed significant improvements in the liver and kidney functions as compared to those in the infected group or S- and Dox-treated groups. Moreover, malondialdehyde level was significantly decreased, while superoxide dismutase and catalase activities were significantly increased in the sera of (S+Q)-treated group in comparison to other treated groups. The spleen recovery in the (S+Q)-treated group was observed with the disappearance of S. aureus colonies as compared to the infected mice. In conclusion, the in vivo treatment of S. aureus infection with S+Q combination decreased the sulfamethoxazole side effects while increasing its antibacterial activity, which supported the therapeutic use of this combination in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

References

  1. J.-P. Gaudillière, Bull. Hist Med, 83(1), 218 – 220 (2009).

    Google Scholar 

  2. S. Jones, Nat. Biotechnol., 30(6), 333 – 333 (2012).

    Google Scholar 

  3. L. L. Brunton, J. S. Lazo, K. Parker, et al., Ann. Pharmacother., 40(6), 1218 (2006).

    Google Scholar 

  4. S. R. M. Bushby and G. H. Hitchings, Br. J. Pharm. Chemother., 33(1), 72 – 90 (1968).

    CAS  Google Scholar 

  5. M. J. ONeil, P. E. Heckelman, C. B. Koch, et al., The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, Merck & Co., Whitehouse Station, NJ, USA. (2006), pp. 1525 – 1535.

    Google Scholar 

  6. M. A. Kielhofner, Tex. Heart. Inst. J., 17(2), 86 – 93 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. T. P. T. Cushnie and A. J. Lamb, Int. J. Antimicrob. Agents, 26(5), 343 – 356 (2005).

    CAS  PubMed  Google Scholar 

  8. H. Liu, Y. Mou, J. Zhao, et al, Molecules, 15(11), 7933 – 7945 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. L. Zhou, D. Li, J. Wang, et al, Nat. Prod. Res., 21(4), 283 – 291 (2007).

    CAS  PubMed  Google Scholar 

  10. V. Chobot, J. Agric. Food Chem., 58(4), 2088 – 2094 (2010).

    CAS  Google Scholar 

  11. L. Sampson, E. Rimm, P. C. H. Hollman, et al., J. Am. Diet. Assoc., 102(10), 1414 – 1420 (2002).

    PubMed  Google Scholar 

  12. R. J. Anderson, P. W. Groundwater, A. Todd, et al., Antibacterial Agents: Chemistry, Mode of Action, Mechanisms of Resistance and Clinical Applications, John Wiley & Sons (2012), pp. 127 – 140.

  13. M. Lesjak, I. Beara, N.Simin, et al., J. Funct. Foods, No. 40, 68 – 75 (2018).

  14. S. C. Cheng, Y. H. Wu, W. C. Huang, et al., Cytokine, No. 116, 48 – 60 (2019).

    CAS  PubMed  Google Scholar 

  15. K. Takashima, M. Matsushima, K. Hashimoto, et al., Respir. Res., 15(1),150 (2014).

    PubMed  PubMed Central  Google Scholar 

  16. M. Amin, K. S. Putra, I. F. Amin, et al., Biol. Med. Nat. Prod. Chem., 7(1), 27 – 31 (2018).

    Google Scholar 

  17. Y. Su, L. Ma, Y. Wen, et al., Molecules, 19(8), 12630 – 12639 (2014).

    PubMed  PubMed Central  Google Scholar 

  18. K. A. Ohemeng, C. F. Schwender, K. P. Fu, et al., Bioorg. Med. Chem. Lett., 3(2), 225 – 230 (1993).

    CAS  Google Scholar 

  19. Z. C. Xing, W. Meng, J. Yuan, et al., J. Nanomater., No. 2012, 1 – 7 (2012).

  20. O. K. Mirzoeva, R. N. Grishanin and P. C. Calder, Microbiol. Res., 152(3), 239 – 246 (1997).

    CAS  PubMed  Google Scholar 

  21. I. Hirai, M. Okuno, R. Katsuma, et al., Int. J. Food. Sci. Technol., 45(6), 1250 – 1254 (2010).

    CAS  Google Scholar 

  22. M. K. Sakharkar, P. Jayaraman, W. Mar Soe, et al., J. Microbiol. Immunol. Infect., 42(5), 364 – 370 (2009).

    CAS  PubMed  Google Scholar 

  23. B. M. Kyaw, S. Arora and C. S. Lim, Braz. J. Microbiol., 43(3), 938 – 945 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. M. Amin, M. Khurram, B. Khattak, et al., BMC Complement. Altern. Med., No. 15, 59 (2015).

  25. M. U. Amin, M. Khurram, T. A. Khan, et al., Int. J. Mol. Sci., 17(11), 1947 (2016).

    Google Scholar 

  26. G. M. Garrity, D. J. Brenner, N. R. Krieg, et al., Bergeys Manual Of Systematic Bacteriology, Springer, New York (2005), Vol. 2, Part B.

  27. A. L. Barry, W. A. Craig, H. Nadler, et al., Methods for Determining Bactericidal Activity of Antimicrobial Agents, Approved Guideline, Clinical and Laboratory Standards Institute, NCCLS (1999), Vol. 19, No. 18.

  28. S. C. Becerra, D. C. Roy, C. J. Sanchez, et al., BMC Res. Notes, No. 19, 1 – 10 (2016).

  29. P. G. Engelkirk and J. L. Duben-Engelkirk, Laboratory Diagnosis of Infectious Diseases, Baltimore, Wolters Kluwer Health, Lippincott Williams & Wilkins, (2008) pp. 124 – 140.

    Google Scholar 

  30. A. Bauer, W. Kirby, J. Sherris, et al., Am. J. Clin. Pathol., 1(6), 451 – 459 (1972).

    Google Scholar 

  31. Methods for Dilution Antimicrobial Susceptibility Tests forBacteria That Grow Aerobically, Approv. Stand. Ed. CLSI Doc., M07-A10, Clinical and Laboratory Standards Institute (2015), Vol. 35, pp 1 – 87.

  32. L. Yao, J. W. Berman, S. M. Factor, et al., Infect. Immun., 65(9), 3889 – 3895, (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. M. Tsuji, Y. Ishii, A. Ohno, et al., Antimicrob. Agents Chemother., 42(1) 94 – 99, (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. O. A. Igbeneghu, E. O. Iwalewa and A. Lamikanra, Phyther. Res., 21, 67 – 71 (2007).

    CAS  Google Scholar 

  35. H. K, Kim, D. Missiakas and O. Schneewind, Immunol. Methods, No. 410, 88 – 99 (2014).

  36. R. Gupta, I. Kazmi, M. Afzal, et al., Mol. Cell Biochem., 384, 279 – 285 (2013).

    CAS  PubMed  Google Scholar 

  37. M. A. Indap, S. C. Bhosle, A. D. Shinde, et al., Indian J. Pharm. Sci., No. 1, 570 – 574 (2006).

  38. M. Fujita, Q. Ye, H. Ouchi, et al., Antimicrob. Agents Chemother., No. 50, 739 – 743 (2006).

  39. C. Bell, in: Clinical Guide to Laboratory Tests, Ed. by Norbert W. Tietz (1995); Transfusion, Vol. 35, Issue 11, pp. 972 – 972.

  40. E. R. Jaff, New Engl. J. Med., 286(3), 156–157 (1972).

    Google Scholar 

  41. D. E. Stanley, J. Am. Med. Assoc., 282(3). 283 (1999).

    Google Scholar 

  42. J. H. Wilkinson, D. N. Baron, D. W. Moss, et al., J. Clin. Pathol., 25(11), 940 – 944 (1972).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. B. T. Doumas, W. A. Watson and H. G. Biggs, Clin. Chim. Acta, 258(1), 21 – 30 (1997).

    CAS  Google Scholar 

  44. M. Nishikimi, N. Appaji Rao, K. Yagi, Biochem. Biophys. Res. Commun., 46(2), 849 – 854 (1972).

    CAS  PubMed  Google Scholar 

  45. H. Aebi, Methods Enzymol., No. 105, 121 – 126 (1984).

  46. Z. A. Placer, L. L. Cushman and B. C. Johnson, Anal. Biochem., 16(2), 359 – 364 (1966).

    CAS  PubMed  Google Scholar 

  47. G. P. Wormser, G. T. Keusch and R. C. Heel, Drugs, 24(6), 459 – 518 (1982).

    CAS  PubMed  Google Scholar 

  48. S. Hemaiswarya, A. K. Kruthiventi, and M. Doble, Phytomedicine, 15(8), 639 – 652 (2008).

    CAS  PubMed  Google Scholar 

  49. A. M. L. Hossion, N. Otsuka, R. K. Kandahary, et al., Bioorg. Med. Chem. Lett., 20(17), 5349 – 5352 (2010).

    CAS  PubMed  Google Scholar 

  50. Y. Xie, W. Yang, F. Tang, et al., Curr. Med. Chem., 22(1), 132 – 149 (2014).

    Google Scholar 

  51. I. Hirai, M. Okuno, R. Katsuma, et al., Int. J. Food. Sci. Technol., 45(6), 1250 – 1254 (2010).

    CAS  Google Scholar 

  52. H. Jaeschke, C. D. Williams, M. R. McGill, et al., Food. Chem. Toxicol., No. 55, 279 – 289 (2013).

  53. G. Ibrahim Qader, R. Aziz, Z. Ahmed, et al., Am. J. Pharmacol. Sci., 2(3), 56 – 60 (2014).

    Google Scholar 

  54. I. M. S. Santos, A. da R. Tome G. B. Saldanha, et al., Oxid. Med. Cell Longev., 2(4), 214 – 221 (2009).

  55. M. Bagchi, D. Bagchi, E, Adickes, et al., J. Environ. Pathol. Toxicol. Oncol. Off. Organ. Int. Soc. Environ. Toxicol. Cancer., 14(2), 61 – 68 (1995).

    CAS  Google Scholar 

  56. L. Ashakumary and P. L. Vijayammal, J. Appl. Toxicol., 16(4), 305 – 308 (1996).

    CAS  Google Scholar 

  57. C. G. M. Heijnen, G. R. M. M. Haenen, F. A. A. Van Acker, et al., Toxicol Vitr., 15(1), 3 – 6 (2001).

    CAS  Google Scholar 

  58. P. C. Hollman, J. M. van Trijp, M. N. C. Buysman, et al., FEBS Lett., 418(1 – 2), 152 – 156 (1997).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors appreciate the assistance of Dr. Baher El-Nogoumy, microbiology lecturer (Microbiology Department, Faculty of Science, Kafrelsheikh University, Kafrelsheikh, Egypt) for his help in identification of clinical isolates in this study.

Funding

The authors declare that there has been no funding.

Author information

Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt

    Heba A. Sahyon & Eman N. M. Ramadan

  2. Chemistry Department, Faculty of Science, Damietta University, Damietta, 34518, Egypt

    Mohammad M. A. Mashaly

Authors
  1. Heba A. Sahyon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eman N. M. Ramadan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad M. A. Mashaly
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heba A. Sahyon.

Ethics declarations

Mice were handled according to the experimental practice and standards approved by the institutional ethical committee (IEC) of Kafrelsheikh University, Egypt. The authors represented a new University and did not get an approval number yet. There were no experiments on human subjects.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sahyon, H.A., Ramadan, E.N.M. & Mashaly, M.M.A. Synergistic Effect of Quercetin in Combination with Sulfamethoxazole as New Antibacterial Agent: In Vitro and In Vivo Study. Pharm Chem J 53, 803–813 (2019). https://doi.org/10.1007/s11094-019-02083-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11094-019-02083-z

Keywords

Search

Navigation