Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지
DOI QR코드

DOI QR Code

Pulegone Exhibits Anti-inflammatory Activities through the Regulation of NF-κB and Nrf-2 Signaling Pathways in LPS-stimulated RAW 264.7 cells

  • Roy, Anupom (Department of Food and Life Science, Pukyong National University) ;
  • Park, Hee-Juhn (Department of Pharmaceutical Engineering, Sangji University) ;
  • Abdul, Qudeer Ahmed (Department of Food and Life Science, Pukyong National University) ;
  • Jung, Hyun Ah (Department of Food Science and Human Nutrition, Chonbuk National University) ;
  • Choi, Jae Sue (Department of Food and Life Science, Pukyong National University)
  • Received : 2017.12.14
  • Accepted : 2018.01.20
  • Published : 2018.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Pulegone is a naturally occurring organic compound obtained from essential oils from a variety of plants. The aim of this study was to investigate the anti-inflammatory effects through the inhibitory mechanism of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), nuclear factor kappa B ($NF-{\kappa}B$), mitogen-activated protein kinases (MAPK) pathways and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase (HO)-1 pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results revealed that pulegone significantly inhibited NO production as well as iNOS and COX-2 expressions. Meanwhile, western blot analysis showed that pulegone down-regulated LPS-induced $NF-{\kappa}B$ and MAPKs activation in RAW 264.7 cells. Furthermore, the selected compound suppressed LPS-induced intracellular ROS production in RAW 264.7 cells, while the expression of stress response gene, HO-1, and its transcriptional activator, Nrf-2 was upregulated upon pulegone treatment. Taking together, these findings provided that pulegone inhibited the LPS-induced expression of inflammatory mediators via the down-regulation iNOS, COX-2, $NF-{\kappa}B$, and MAPKs signaling pathways as well as up-regulation of Nrf-2/HO-1 indicating that pulegone has a potential therapeutic and preventive application in various inflammatory diseases.

Keywords

References

  1. Choudhari, A. S.; Raina, P.; Deshpande, M. M.; Wali, A. G.; Zanwar, A.; Bodhankar, S. L.; Kaul-Ghanekar, R. J. Ethnopharmacol. 2013, 150, 215-222. https://doi.org/10.1016/j.jep.2013.08.025
  2. Joung, E. -J.; Lee, B.; Gwon, W. -G.; Shin, T.; Jung, B. -M.; Yoon, N. -Y.; Choi, J. -S.; Oh, C. W.; Kim, H. -R. Int. Immunopharmacol. 2015, 29, 693-700. https://doi.org/10.1016/j.intimp.2015.09.007
  3. Giuliani, C.; Napolitano, G.; Bucci, I.; Montani, V.; Monaco, F. Clin. Ter. 2001, 152, 249-253.
  4. May, M. J.; Ghosh, S. Immunol. Today 1998, 19, 80-88. https://doi.org/10.1016/S0167-5699(97)01197-3
  5. Tak, P. P.; Firestein, G. S. J. Clin. Invest. 2001, 107, 7-11. https://doi.org/10.1172/JCI11830
  6. Kim, A. -R.; Lee, M. -S.; Shin, T. -S.; Hua, H.; Jang, B. -C.; Choi, J. -S.; Byun, D. -S.; Utsuki, T.; Ingram, D.; Kim, H. -R. Toxicol. in Vitro 2011, 25, 1789-1795. https://doi.org/10.1016/j.tiv.2011.09.012
  7. Pae, H. -O.; Chung, H. -T. Immune Netw. 2009, 9, 12-19. https://doi.org/10.4110/in.2009.9.1.12
  8. Lee, I. -S.; Lim, J.; Gal, J.; Kang, J. C.; Kim, H. J.; Kang, B. Y.; Choi, H. J. Neurochem. Int. 2011, 58, 153-160. https://doi.org/10.1016/j.neuint.2010.11.008
  9. Taha, R.; Blaise, G. Funct. Food Health Dis. 2014, 4, 510-523.
  10. Bakkali, F.; Averbeck, S.; Averbeck, D.; Idaomar, M. Food Chem. Toxicol. 2008, 46, 446-475. https://doi.org/10.1016/j.fct.2007.09.106
  11. Sullivan, J. B.; Rumack, B. H.; Thomas, H.; Peterson, R. G.; Bryson, P. J. Am. Med. Assoc. 1979, 242, 2873-2874. https://doi.org/10.1001/jama.1979.03300260043027
  12. Choi, J. S.; Song, B. -M.; Park, H. -J. Kor. J. Pharmacogn. 2016, 47, 192-196.
  13. Kumar, P.; Mishra, S.; Malik, A.; Satya, S. Ind. Crops Prod. 2011, 34, 802-817. https://doi.org/10.1016/j.indcrop.2011.02.019
  14. Brahmi, F.; Abdenour, A.; Bruno, M.; Silvia, P.; Alessandra, P.; Danilo, F.; Drifa, Y. -G.; Fahmi, E. M.; Khodir, M.; Mohamed, C. Ind. Crops Prod. 2016, 88, 96-105. https://doi.org/10.1016/j.indcrop.2016.03.002
  15. Ertas, A.; Goren, A. C.; Hasimi, N.; Tolan, V.; Kolak, U. Rec. Nat. Prod. 2015, 9, 105-115.
  16. Jung, H. A.; Roy, A.; Abdul, Q. A.; Kim, H. R.; Park, H. J.; Choi, J. S. Nat. Prod. Sci. 2017, 23, 183-191. https://doi.org/10.20307/nps.2017.23.3.183
  17. Yim, V. W. C.; Ng, A. K. Y.; Tsang, H. W. H.; Leung, A. Y. J. Altern. Complement. Med. 2009, 15, 187-195. https://doi.org/10.1089/acm.2008.0333
  18. Moss, M.; Hewitt, S.; Moss, L.; Wesnes, K. Int. J. Neurosci. 2008, 118, 59-77. https://doi.org/10.1080/00207450601042094
  19. Nath, S. S.; Pandey, C.; Roy, D. Indian J. Anaesth. 2012, 56, 582-584. https://doi.org/10.4103/0019-5049.104585
  20. Di Stasi, L. C.; Oliveira, G. P.; Carvalhaes, M. A.; Queiroz-Junior, M.; Tien, O. S.; Kakinami, S. H.; Reis, M. S. Fitoterapia 2002, 73, 69-91. https://doi.org/10.1016/S0367-326X(01)00362-8
  21. Beikmohammadi, M. World Appl. Sci. J. 2011, 12, 1635-1638.
  22. McClanahan, R. H.; Thomassen, D.; Slattery, J. T.; Nelson, S. D. Chem. Res. Toxicol. 1989, 2, 349-355. https://doi.org/10.1021/tx00011a013
  23. Bakerink, J. A.; Gospe, S. M. Jr.; Dimand, R. J.; Eldridge, M. W. Pediatrics 1996, 98, 944-947.
  24. de Sousa, D. P.; Nobrega, F. F. F.; de Lima, M. R. V.; de Almeida, R. N. Naturforsch. C, 2011, 66, 353-359. https://doi.org/10.5560/ZNC.2011.66c0353
  25. Umezu, T. Pharmacol. Biochem. Behav. 2010, 94, 497-502. https://doi.org/10.1016/j.pbb.2009.11.001
  26. Yao, Q. S.; Chiou, G. C. Zhongguo Yao Li Xue Bao 1993, 14, 13-17.
  27. Wen, T. Q.; Sang, W. T.; Xu, F.; Wang, F.; Zeng, N. Zhongguo Zhong Yao Za Zhi 2016, 41, 4642-4647.
  28. Meda, L.; Cassatella, M. A.; Szendrei, G. I.; Otvos, L. Jr.; Baron, P.; Villalba, M.; Ferrari, D.; Rossi, F. Nature 1995, 374, 647-650. https://doi.org/10.1038/374647a0
  29. Dandona, P.; Chaudhuri, A.; Dhindsa, S. Diabetes Care 2010, 33, 1686-1687.
  30. Marks-Konczalik, J.; Chu, S. C.; Moss, J. J. Biol. Chem. 1998, 273, 22201-22208. https://doi.org/10.1074/jbc.273.35.22201
  31. Islam, M. N.; Choi, R. J.; Jin, S. E.; Kim, Y. S.; Ahn, B. R.; Zhao, D.; Jung, H. A.; Choi, J. S. J. Ethnopharmacol. 2012, 144, 175-181. https://doi.org/10.1016/j.jep.2012.08.048
  32. Chen, J. J.; Huang, W. C.; Chen, C. C. Mol. Biol. Cell 2005, 16, 5579-5591. https://doi.org/10.1091/mbc.e05-08-0778
  33. Kaminska, B. Biochim. Biophys. Acta 2005, 1754, 253-262. https://doi.org/10.1016/j.bbapap.2005.08.017
  34. Hancock, J. T.; Desikan, R.; Neill, S. J. Biochem. Soc. Trans. 2001, 29, 345-349. https://doi.org/10.1042/bst0290345
  35. Choi, S. -Y.; Hwang, J. -H.; Ko, H. -C.; Park, J. -G.; Kim, S. -J. J. Ethnopharmacol. 2007, 113, 149-155. https://doi.org/10.1016/j.jep.2007.05.021
  36. Siomek, A. Acta Biochem. Pol. 2012, 59, 323-331.
  37. Ryan, K. A.; Smith, M. F. Jr.; Sanders, M. K.; Ernst, P. B. Infect. Immun. 2004, 72, 2123-2130. https://doi.org/10.1128/IAI.72.4.2123-2130.2004
  38. Kim, J. -H.; Choo, Y. -Y.; Tae, N.; Min, B. -S.; Lee, J. -H. Int. Immunopharmacol. 2014, 22, 420-426. https://doi.org/10.1016/j.intimp.2014.07.025
  39. Lee, M. -Y.; Lee, J. -A.; Seo, C. -S.; Ha, H.; Lee, H.; Son, J. -K.; Shin, H. -K. Food Chem. Toxicol. 2011, 49, 1047-1055. https://doi.org/10.1016/j.fct.2011.01.010
  40. Paine, A.; Eiz-Vesper, B.; Blasczyk, R.; Immenschuh, S. Biochem. Pharmacol. 2010, 80, 1895-1903. https://doi.org/10.1016/j.bcp.2010.07.014
  41. Tsoyi, K.; Lee, T. Y.; Lee, Y. S.; Kim, H. J.; Seo, H. G.; Lee, J. H.; Chang, K. C. Mol. Pharmacol. 2009, 76, 173-182.
  42. Auerbach, S. S.; Elmore, S. A.; Bishop, J. B.; Bucher, J. R.; Chan, P. C.; Chhabra, R. S.; Foster, P. M.; Herbert, R. A.; Hooth, M. J.; King-Herbert, A. P.; Kissling, G. E.; Malarkey, D. E.; Roycroft, J. H.; Sanders, J. M.; Smith, C. S.; Travlos, G. S.; Walker, N. J.; Witt, K. L.; Hejtmancik, M. R.; Sells, D. M.; Skowronek, A. J.; Toft, J. D. II; Hamlin, M. H. II; Brix, A. E.; Hard, G. C.; Kolenda-Roberts, H. M.; Peckham, J. C.; Wolfe, G. W.; Seung, H. S.; Brecher, S.; Iyer, S.; Tharakan, V. S.; Morrison, J. P.; Elmore, S. A.; Flake, G. P.; Hard, G. C.; Kolenda-Roberts, H. M.; Malarkey, D. E.; Maronpot, R. R.; Peckham, J. C.; Morrison, J. P.; Belpoggi, F.; Brix, A. E.; Elmore, S. A.; Flake, G. P.; Hard, G. C.; Herbert, R. A.; Malarkey, D. E.; Maronpot, R. R.; Wakamatsu, N.; Crockett, P. W.; Betz, L. J.; McGowan, K. P.; Gunnels, S. R.; Coker, K. K.; Harper, L. M.; Serbus, D. C. Natl. Toxicol. Program Tech. Rep. Ser. 2011, 563, 1-201.

Cited by

  1. Organic acid conjugated phenolic compounds of hardy kiwifruit (Actinidia arguta) and their NF-κB inhibitory activity vol.308, pp.None, 2018, https://doi.org/10.1016/j.foodchem.2019.125666
  2. Apoptosis Induced by Ziziphora tenuior Essential Oil in Human Colorectal Cancer Cells vol.2021, pp.None, 2021, https://doi.org/10.1155/2021/5522964
  3. Chemical Characterization and Antioxidant, Antimicrobial, and Insecticidal Properties of Essential Oil from Mentha pulegium L. vol.2021, pp.None, 2018, https://doi.org/10.1155/2021/1108133