DOI QR코드

DOI QR Code

Phosphorylation of Akt Mediates Anti-Inflammatory Activity of 1-p-Coumaroyl ${\beta}$-D-Glucoside Against Lipopolysaccharide-Induced Inflammation in RAW264.7 Cells

  • Vo, Van Anh (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Lee, Jae-Won (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kim, Ji-Young (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Park, Jun-Ho (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Lee, Hee Jae (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kim, Sung-Soo (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kwon, Yong-Soo (College of Pharmacy, Kangwon National University) ;
  • Chun, Wanjoo (Department of Pharmacology, College of Medicine, Kangwon National University)
  • 투고 : 2013.11.20
  • 심사 : 2013.12.31
  • 발행 : 2014.02.28

초록

Hydroxycinnamic acids have been reported to possess numerous pharmacological activities such as antioxidant, anti-inflammatory, and anti-tumor properties. However, the biological activity of 1-p-coumaroyl ${\beta}$-D-glucoside (CG), a glucose ester derivative of p-coumaric acid, has not been clearly examined. The objective of this study is to elucidate the anti-inflammatory action of CG in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In the present study, CG significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. CG also inhibited LPS-induced secretion of pro-inflammatory cytokines, IL-$1{\beta}$ and TNF-${\alpha}$. In addition, CG significantly suppressed LPS-induced degradation of $I{\kappa}B$. To elucidate the underlying mechanism by which CG exerts its anti-inflammatory action, involvement of various signaling pathways were examined. CG exhibited significantly increased Akt phosphorylation in a concentration-dependent manner, although MAPKs such as Erk, JNK, and p38 appeared not to be involved. Furthermore, inhibition of Akt/PI3K signaling pathway with wortmannin significantly, albeit not completely, abolished CG-induced Akt phosphorylation and anti-inflammatory actions. Taken together, the present study demonstrates that Akt signaling pathway might play a major role in CG-mediated anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells.

키워드

참고문헌

  1. Nagasaka R, Chotimarkorn C, Shafiqul IM, Hori M, Ozaki H, Ushio H. Anti-inflammatory effects of hydroxycinnamic acid derivatives. Biochem Biophys Res Commun. 2007;358:615-619. https://doi.org/10.1016/j.bbrc.2007.04.178
  2. Steinbrecher T, Hrenn A, Dormann KL, Merfort I, Labahn A. Bornyl (3,4,5-trihydroxy)-cinnamate--an optimized human neutrophil elastase inhibitor designed by free energy calculations. Bioorg Med Chem. 2008;16:2385-2390. https://doi.org/10.1016/j.bmc.2007.11.070
  3. Kim YC. Neuroprotective phenolics in medicinal plants. Arch Pharm Res. 2010;33:1611-1632. https://doi.org/10.1007/s12272-010-1011-x
  4. Teixeira J, Gaspar A, Garrido EM, Garrido J, Borges F. Hydroxycinnamic acid antioxidants: an electrochemical overview. Biomed Res Int. 2013;2013:251754.
  5. Lee JW, Bae CJ, Choi YJ, Kim SI, Kim NH, Lee HJ, Kim SS, Kwon YS, Chun W. 3,4,5-trihydroxycinnamic acid inhibits LPS-Induced iNOS expression by suppressing NF-${\kappa}B$ activation in BV2 microglial cells. Korean J Physiol Pharmacol. 2012;16:107-112. https://doi.org/10.4196/kjpp.2012.16.2.107
  6. Lee JW, Choi YJ, Park JH, Sim JY, Kwon YS, Lee HJ, Kim SS, Chun W. 3,4,5-trihydroxycinnamic acid inhibits lipopolysaccharide- induced inflammatory response through the activation of Nrf2 pathway in BV2 microglial cells. Biomol Ther (Seoul). 2013;21:60-65. https://doi.org/10.4062/biomolther.2012.091
  7. Lee JW, Cheong IY, Kim HS, Lee JJ, Lee YS, Kwon YS, Kim MJ, Lee HJ, Kim SS, Chun W. Anti-inflammatory activity of 1-docosanoyl cafferate isolated from rhus verniciflua in LPSstimulated BV2 microglial cells. Korean J Physiol Pharmacol. 2011;15:9-15. https://doi.org/10.4196/kjpp.2011.15.1.9
  8. Lee Y, Shin DH, Kim JH, Hong S, Choi D, Kim YJ, Kwak MK, Jung Y. Caffeic acid phenethyl ester-mediated Nrf2 activation and IkappaB kinase inhibition are involved in NFkappaB inhibitory effect: structural analysis for NFkappaB inhibition. Eur J Pharmacol. 2010;643:21-28. https://doi.org/10.1016/j.ejphar.2010.06.016
  9. Hooper SN, Jurgens T, Chandler RF, Stevens MFG. Methyl p-coumarate: A cytotoxic constituent from Comptonia peregrina. Phytochemistry. 1984;23:2096-2209. https://doi.org/10.1016/S0031-9422(00)84992-4
  10. Kwon YS, Kim CM. Antioxidant constituents from the stem of Sorghum bicolor. Arch Pharm Res. 2003;26:535-539. https://doi.org/10.1007/BF02976877
  11. Kubo I, Nihei K, Tsujimoto K. Methyl p-coumarate, a melanin formation inhibitor in B16 mouse melanoma cells. Bioorg Med Chem. 2004;12:5349-5354. https://doi.org/10.1016/j.bmc.2004.07.052
  12. Lee M, Lee HH, Lee JK, Ye SK, Kim SH, Sung SH. Antiadipogenic activity of compounds isolated from Idesia polycarpa on 3T3-L1 cells. Bioorg Med Chem Lett. 2013;23:3170-3174. https://doi.org/10.1016/j.bmcl.2013.04.011
  13. Zhang Y, Seeram NP, Lee R, Feng L, Heber D. Isolation and identification of strawberry phenolics with antioxidant and human cancer cell antiproliferative properties. J Agric Food Chem. 2008;56:670-675. https://doi.org/10.1021/jf071989c
  14. Jeon SH, Chun W, Choi YJ, Kwon YS. Cytotoxic constituents from the bark of Salix hulteni. Arch Pharm Res. 2008;31:978-982. https://doi.org/10.1007/s12272-001-1255-9
  15. Rehman MU, Yoshihisa Y, Miyamoto Y, Shimizu T. The anti-inflammatory effects of platinum nanoparticles on the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages. Inflamm Res. 2012;61:1177-1185. https://doi.org/10.1007/s00011-012-0512-0
  16. Kim YJ, Shin Y, Lee KH, Kim TJ. Anethum graveloens flower extracts inhibited a lipopolysaccharide-induced inflammatory response by blocking iNOS expression and NF-${\kappa}B$ activity in macrophages. Biosci Biotechnol Biochem. 2012;76:1122-1127.
  17. Itharat A, Hiransai P. Dioscoreanone suppresses LPS-induced nitric oxide production and inflammatory cytokine expression in RAW 264.7 macrophages by NF-${\kappa}B$ and ERK1/2 signaling transduction. J Cell Biochem. 2012;113:3427-3435. https://doi.org/10.1002/jcb.24219
  18. Rietschel ET, Brade H. Bacterial endotoxins. Sci Am. 1992;267:54-61.
  19. Sweet MJ, Hume DA. Endotoxin signal transduction in macrophages. J Leukoc Biol. 1996;60:8-26.
  20. Ock J, Kim S, Suk K. Anti-inflammatory effects of a fluorovinyloxyacetamide compound KT-15087 in microglia cells. Pharmacol Res. 2009;59:414-422. https://doi.org/10.1016/j.phrs.2009.02.008
  21. Zheng LT, Ryu GM, Kwon BM, Lee WH, Suk K. Antiinflammatory effects of catechols in lipopolysaccharide- stimulated microglia cells: inhibition of microglial neurotoxicity. Eur J Pharmacol. 2008;588:106-113. https://doi.org/10.1016/j.ejphar.2008.04.035
  22. Fresco P, Borges F, Diniz C, Marques MP. New insights on the anticancer properties of dietary polyphenols. Med Res Rev. 2006;26:747-766. https://doi.org/10.1002/med.20060
  23. Razzaghi-Asl N, Garrido J, Khazraei H, Borges F, Firuzi O. Antioxidant properties of hydroxycinnamic acids: a review of structure-activity relationships. Curr Med Chem. 2013;20: 4436-4450. https://doi.org/10.2174/09298673113209990141
  24. Navaneethan D, Rasool M. p-Coumaric acid, a common dietary polyphenol, protects cadmium chloride-induced nephrotoxicity in rats. Ren Fail. 2013. [Epub ahead of print]
  25. Lee JW, Cheong IY, Kim HS, Lee JJ, Lee YS, Kwon YS, Kim MJ, Lee HJ, Kim SS, Chun W. Anti-inflammatory activity of 1-docosanoyl cafferate isolated from rhus verniciflua in LPSstimulated BV2 microglial cells. Korean J Physiol Pharmacol. 2011;15:9-15. https://doi.org/10.4196/kjpp.2011.15.1.9
  26. Fürer K, Raith M, Brenneisen R, Mennet M, Simões-Wüst AP, von Mandach U, Hamburger M, Potterat O. Two new flavonol glycosides and a metabolite profile of Bryophyllum pinnatum, a phytotherapeutic used in obstetrics and gynaecology. Planta Med. 2013;79:1565-1571. https://doi.org/10.1055/s-0033-1350808
  27. Hou L, Zhou B, Yang L, Liu ZL. Inhibition of free radical initiated peroxidation of human erythrocyte ghosts by flavonols and their glycosides. Org Biomol Chem. 2004;2:1419-1423. https://doi.org/10.1039/b401550a
  28. Vo VA, Lee JW, Chang JE, Kim JY, Kim NH, Lee HJ, Kim SS, Chun W, Kwon YS. Avicularin inhibits lipopolysaccharideinduced inflammatory response by suppressing ERK phosphorylation in RAW 264.7 macrophages. Biomol Ther (Seoul). 2012;20:532-537. https://doi.org/10.4062/biomolther.2012.20.6.532
  29. Akao T, Kobashi K, Aburada M. Enzymic studies on the animal and intestinal bacterial metabolism of geniposide. Biol Pharm Bull. 1994;17:1573-1576. https://doi.org/10.1248/bpb.17.1573
  30. Arts IC, Sesink AL, Faassen-Peters M, Hollman PC. The type of sugar moiety is a major determinant of the small intestinal uptake and subsequent biliary excretion of dietary quercetin glycosides. Br J Nutr. 2004;91:841-847. https://doi.org/10.1079/BJN20041123
  31. Ha YM, Ham SA, Kim YM, Lee YS, Kim HJ, Seo HG, Lee JH, Park MK, Chang KC. $\beta$1-adrenergic receptor-mediated HO-1 induction, via PI3K and p38 MAPK, by isoproterenol in RAW 264.7 cells leads to inhibition of HMGB1 release in LPSactivated RAW 264.7 cells and increases in survival rate of CLP-induced septic mice. Biochem Pharmacol. 2011;82:769-777. https://doi.org/10.1016/j.bcp.2011.06.041
  32. Jung WK, Lee DY, Park C, Choi YH, Choi I, Park SG, Seo SK, Lee SW, Yea SS, Ahn SC, Lee CM, Park WS, Ko JH, Choi IW. Cilostazol is anti-inflammatory in BV2 microglial cells by inactivating nuclear factor-kappaB and inhibiting mitogenactivated protein kinases. Br J Pharmacol. 2010;159:1274-1285. https://doi.org/10.1111/j.1476-5381.2009.00615.x
  33. O'Connell MA, Bennett BL, Mercurio F, Manning AM, Mackman N. Role of IKK1 and IKK2 in lipopolysaccharide signaling in human monocytic cells. J Biol Chem. 1998;273: 30410-30414. https://doi.org/10.1074/jbc.273.46.30410
  34. Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cell Signal. 2001;13:85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  35. Lee JW, Kim NH, Kim JY, Park JH, Shin SY, Kwon YS, Lee HJ, Kim SS, Chun W. Aromadendrin inhibits lipopolysaccharide- induced nuclear translocation of NF-${\kappa}B$ and phosphorylation of JNK in RAW 264.7 macrophage cells. Biomol Ther (Seoul). 2013;21:216-221. https://doi.org/10.4062/biomolther.2013.023
  36. Kuprash DV, Udalova IA, Turetskaya RL, Rice NR, Nedospasov SA. Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages. Oncogene. 1995;11:97-106.
  37. Siebenlist U, Franzoso G, Brown K. Structure, regulation and function of NF-kappa B. Annu Rev Cell Biol. 1994;10:405-455. https://doi.org/10.1146/annurev.cb.10.110194.002201
  38. Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol. 2002;2:725-734. https://doi.org/10.1038/nri910
  39. Karin M, Takahashi T, Kapahi P, Delhase M, Chen Y, Makris C, Rothwarf D, Baud V, Natoli G, Guido F, Li N. Oxidative stress and gene expression: the AP-1 and NF-kappaB connections. Biofactors. 2001;15:87-89. https://doi.org/10.1002/biof.5520150207
  40. Moon DO, Park SY, Lee KJ, Heo MS, Kim KC, Kim MO, Lee JD, Choi YH, Kim GY. Bee venom and melittin reduce proinflammatory mediators in lipopolysaccharide-stimulated BV2 microglia. Int Immunopharmacol. 2007;7:1092-1101. https://doi.org/10.1016/j.intimp.2007.04.005
  41. Zheng LT, Ock J, Kwon BM, Suk K. Suppressive effects of flavonoid fisetin on lipopolysaccharide-induced microglial activation and neurotoxicity. Int Immunopharmacol. 2008;8:484-494. https://doi.org/10.1016/j.intimp.2007.12.012

피인용 문헌

  1. Crocin Inhibits Oxidative Stress and Pro-inflammatory Response of Microglial Cells Associated with Diabetic Retinopathy Through the Activation of PI3K/Akt Signaling Pathway vol.61, pp.4, 2014, https://doi.org/10.1007/s12031-017-0899-8
  2. Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review vol.22, pp.2, 2014, https://doi.org/10.3390/molecules22020281
  3. Anti-inflammatory effect of tranexamic acid against trauma-hemorrhagic shock-induced acute lung injury in rats vol.67, pp.3, 2018, https://doi.org/10.1538/expanim.17-0143
  4. Anti-Inflammatory Activity of Populus deltoides Leaf Extract via Modulating NF-κB and p38/JNK Pathways vol.19, pp.12, 2014, https://doi.org/10.3390/ijms19123746
  5. Procyanidin A1 Alleviates Inflammatory Response induced by LPS through NF-κB, MAPK, and Nrf2/HO-1 Pathways in RAW264.7 cells vol.9, pp.1, 2014, https://doi.org/10.1038/s41598-019-51614-x
  6. Reconsideration of Classical Antibiotic Lincomycin: Anti-inflammatory Effect in LPS-stimulated RAW 264.7 Cells vol.48, pp.3, 2020, https://doi.org/10.4014/mbl.2002.02015
  7. Glycosylated Phenols and an Unprecedented Diacid from the Saudi Plant Cissus rotundifolia vol.83, pp.11, 2020, https://doi.org/10.1021/acs.jnatprod.0c00597