Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
권호 표지

Mollugin-mediated Inhibition of Proinflammatory Biomarkers in Lipopolysaccharide-stimulated RAW264.7 Cells

  • Kim, Jin-Kyung (Department of Biomedical Science, Catholic University of Daegu) ;
  • Park, Geun-Mook (Department of Biomedical Science, Catholic University of Daegu) ;
  • Jun, Jong-Gab (Department of Chemistry and Institute of Natural Medicine, Hallym University)
  • Received : 2012.09.26
  • Accepted : 2012.10.18
  • Published : 2012.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Mollugin is the active compound of Rubia cordifolia, a well known herb widely used in alternative medicines for the treatment of various inflammatory diseases including arthritis and uteritis. In the present study, we investigated the anti-inflammatory effects of mollugin in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells. Treatment with mollugin significantly inhibited LPS-induced release of nitric oxide, prostaglandin $E_2$, and inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6. In addition, mollugin suppressed LPS-induced nuclear factor-kappa B (NF-${\kappa}B$) transcriptional activity. These results suggest that mollugin inhibits LPS-induced expression of inflammatory molecules via NF-${\kappa}B$, at least in part, and indicate the potential value of mollugin as a valuable new drug candidate for the treatment of various inflammatory diseases.

Keywords

References

  1. Aggarwal BB, Shishodia S. Suppression of the nuclear factorkappaB activation pathway by spice-derived phytochemicalss: reasoning for seasoning. Ann N Y Acad Sci. 2004. 1030: 434-441. https://doi.org/10.1196/annals.1329.054
  2. Checker R, Sandur SK, Sharma D, Patwardhan RS, Jayakumar S, Kohli V, Sethi G, Aggarwal BB, Sainis KB. Potent antiinflammatory activity of ursolic acid, a triterpenoid antioxidant, is mediated through suppression of $NF-{\kappa}B$, AP-1 and NF-AT. PLoS One. 2012. 7: e31318. https://doi.org/10.1371/journal.pone.0031318
  3. Chen CC. Signal transduction pathways of inflammatory gene expressions and therapeutic implications. Curr Pharm Des. 2006. 12: 3497-3508. https://doi.org/10.2174/138161206778343028
  4. Chung MI, Jou SJ, Cheng HC, Lin CN, Ko FN, Teng CM. Antiplatelet constituents of formosan Rubia akane. J Nat Prod. 1994. 57: 313-316. https://doi.org/10.1021/np50104a020
  5. Falvo JV, Tsytsykova AV, Goldfeld AE. Transcriptional control of the TNF gene. Curr Dir Autoimmun. 2010. 11: 27-60.
  6. Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012. 33: 829-837. https://doi.org/10.1093/eurheartj/ehr304
  7. Gerstein NS, Schulman PM, Gerstein WH, Petersen TR, Tawil I. Should more patients continue aspirin therapy perioperatively?: clinical impact of aspirin withdrawal syndrome. Ann Surg. 2012. 255: 811-819. https://doi.org/10.1097/SLA.0b013e318250504e
  8. Ho LK, Don MJ, Chen HC, Yeh SF, Chen JM. Inhibition of hepatitis B surface antigen secretion on human hepatoma cells. Components from Rubia cordifolia. J Nat Prod. 1996. 59: 330-333. https://doi.org/10.1021/np960200h
  9. Jun Y, Han CR, Choi MS, Bae MA, Woo MH, Kim YH. Effect of mollugin on apoptosis and adipogenesis of 3T3-L1 preadipocytes. Phytother Res. 2011. 25: 724-731. https://doi.org/10.1002/ptr.3329
  10. Jung HW, Oh JS, Lee SH, Liang JL, Kim DH, Rahman AFM, Jahng Y. A facile synthesis of mollugin. Bull Korean Chem Soc. 2007. 28: 1863-1866. https://doi.org/10.5012/bkcs.2007.28.10.1863
  11. Kawasaki Y, Goda Y, Yoshihira K. The mutagenic constituents of Rubia tinctorum. Chem Pharm Bull. 1992. 40: 1504-1509. https://doi.org/10.1248/cpb.40.1504
  12. Kim HP, Son KH, Chang HW, Kang SS. Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci. 2004. 96: 229-245. https://doi.org/10.1254/jphs.CRJ04003X
  13. Kleinert H, Schwarz PM, Förstermann U. Regulation of the expression of inducible nitric oxide synthase. Biol Chem. 2003. 384: 1343-1364.
  14. Kuete V. Potential of Cameroonian plants and derived products against microbial infections: a review. Planta Med. 2010. 76: 1479-1491. https://doi.org/10.1055/s-0030-1250027
  15. Kundu JK, Surh YJ. 2008. Inflammation: gearing the journey to cancer. Mutat Res. 2008. 659: 15-30. https://doi.org/10.1016/j.mrrev.2008.03.002
  16. Li JW, Vederas JC. Drug discovery and natural products: end of an era or an endless frontier? Science. 2009. 325: 161-165. https://doi.org/10.1126/science.1168243
  17. Li X, Stark GR. 2002. NFkappaB-dependent signaling pathways. Exp Hematol. 2002. 30: 285-296. https://doi.org/10.1016/S0301-472X(02)00777-4
  18. Luqman S, Pezzuto JM. NFkappaB: a promising target for natural products in cancer chemoprevention. Phytother Res. 2010. 24: 949-963.
  19. Marec F, Kollarova I, Jegorov A. Mutagenicity of natural anthraquinones from Rubia tinctorum in the Drosophila wing spot test. Planta Med. 2001. 67: 127-131. https://doi.org/10.1055/s-2001-11498
  20. Puangpraphant S, de Mejia EG. Saponins in yerba mate tea (Ilex paraguariensis A. St.-Hil) and quercetin synergistically inhibit iNOS and COX-2 in lipopolysaccharide-induced macrophages through $NF-{\kappa}B$ pathways. J Agric Food Chem. 2009. 57: 8873-8883. https://doi.org/10.1021/jf902255h
  21. Qi LW, Liu EH, Chu C, Peng YB, Cai HX, Li P. Anti-diabetic agents from natural products--an update from 2004 to 2009. Curr Top Med Chem. 2010. 10: 434-457. https://doi.org/10.2174/156802610790980620
  22. Rossol M, Heine H, Meusch U, Quandt D, Klein C, Sweet MJ, Hauschildt S. LPS-induced cytokine production in human monocytes and macrophages. Crit Rev Immunol. 2011. 31: 379-446. https://doi.org/10.1615/CritRevImmunol.v31.i5.20
  23. Salminen A, Kauppinen A, Kaarniranta K. Phytochemicals suppress nuclear factor-${\kappa}B$ signaling: impact on health span and the aging process. Curr Opin Clin Nutr Metab Care. 2012. 15: 23 -28. https://doi.org/10.1097/MCO.0b013e32834d3ae7
  24. Smith WL, Urade Y, Jakobsson PJ. Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis. Chem Rev. 2011. 111: 5821-5865. https://doi.org/10.1021/cr2002992
  25. Stoffel A. The NF-kappaB signalling pathway: a therapeutic target in lymphoid malignancies? Expert Opin Ther Targets. 2005. 9: 1045-1061. https://doi.org/10.1517/14728222.9.5.1045
  26. Vitiello M, Galdiero M, Finamore E, Galdiero S, Galdiero M. $NF-{\kappa}B$ as a potential therapeutic target in microbial diseases. Mol Biosyst. 2012. 8: 1108-1120. https://doi.org/10.1039/c2mb05335g
  27. Wang H, Cho CH. Effect of $NF-{\kappa}B$ signaling on apoptosis in chronic inflammation-associated carcinogenesis. Curr Cancer Drug Targets. 2010. 10: 593-599. https://doi.org/10.2174/156800910791859425
  28. Whitehouse MW. Anti-inflammatory glucocorticoid drugs: reflections after 60 years. Inflammopharmacology. 2011. 19: 1-19. https://doi.org/10.1007/s10787-010-0056-2
  29. Wu KK. Control of COX-2 and iNOS gene expressions by aspirin and salicylate. Thromb Res. 2003. 110: 273-276. https://doi.org/10.1016/S0049-3848(03)00412-2
  30. Yuan JM, Sun C, Butler LM. Tea and cancer prevention: epidemiological studies. Pharmacol Res. 2011. 64: 123-135. https://doi.org/10.1016/j.phrs.2011.03.002
  31. Zauderer MG, Krug LM. Novel therapies in phase II and III trials for malignant pleural mesothelioma. J Natl Compr Canc Netw. 2012. 10: 42-47. https://doi.org/10.6004/jnccn.2012.0007