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Inhibitory effect of Mori Folium ethanol extract on pro-inflammatory mediator in lipopolysaccharide - activated RAW 264.7 cells

상엽(桑葉) 추출물의 LPS로 유도된 RAW 264.7 세포에서의 항염증 효과

  • Received : 2012.04.15
  • Accepted : 2012.04.28
  • Published : 2012.05.30

Abstract

Objectives : Mori Folium is one of the traditional medicinal herb. It was commonly used for sericulture in the world and has been traditionally administered as natural therapeutic agent for the treatment of filariasis, diabetes and dropsy in East Asia. This study investigated an anti-inflammatory potential of Mori Folium ethanol extract (MFE). Methods : We examined the effects of MFE on the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in a murine macrophage cell line, RAW 264.7. Results : MFE inhibited production of NO and $PGE_2$ in a dose dependent manner and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin (IL)-1, IL-6 and tumor necrosis factor-${\alpha}$. As a plausible molecular mechanism, increased degradation of I-${\kappa}B{\alpha}$ and phosphorylation of I-${\kappa}B{\alpha}$, NF-${\kappa}B$ and MAP kinases by LPS were partly blocked by MFE treatment. Conclusions : These results suggest that MFE has an anti-inflammatory therapeutic potential, which may result from inhibition of NF-${\kappa}B$ activation and MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes.

Keywords

Mori Folium;anti-inflammation;iNOS;NF-${\kappa}B$;MAP kinases

References

  1. Robbins SL, Kumar V, Cotran RS. Acute and chronic inflammation : Mitchell S. Pathologic basis of disease. 7th ed. Philadelphia : W. B. Saunders Co. 2006 : 47-86.
  2. Kindt TJ, Goldsby RA, Osborne BA. Innate immunity : Tenney S. Kuby Immunology. 6th ed. New York : Freeman press. 2007 : 52-73.
  3. Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immunol. 2002 ; 20 : 55-72. https://doi.org/10.1146/annurev.immunol.20.091301.131133
  4. The Korean Medical Dictionary Compliation Committee. The Korean Medical Dictionary. Seoul : Jungdam. 1998 : 727.
  5. Kim CM, Shin MG, An DG, Lee KS. The chinese herbal Dictionary. Seoul : Jungdam. 1998 : 2817-21.
  6. Sugimoto M, Arai H, Tamura Y, Murayama T, Khaengkhan P, Nishio T, Ono K, Ariyasu H, Akamizu T, Ueda Y, Kita T, Harada S, Kamei K, Yokode M. Mulberry leaf ameliorates the expression profile of adipocytokines by inhibiting oxidative stress in white adipose tissue in db/db mice. Atherosclerosis. 2009 ; 204 : 388-94. https://doi.org/10.1016/j.atherosclerosis.2008.10.021
  7. Harauma A, Murayama T, Ikeyama K, Sano H, Arai H, Takano R, Kita T, Hara S, Kamei K, Yokode M. Mulberry leaf powder prevents atherosclerosis in apolipoprotein E-deficient mice. Biochem Biophys Res Commun. 2007 ; 358 : 751-6. https://doi.org/10.1016/j.bbrc.2007.04.170
  8. Sattayasai J, Tiamkao S, Puapairoj P. Biphasic effects of Morus alba leaves green tea extract on mice in chronic forced swimming model. Phytother Res. 2008 ; 22 : 487-92. https://doi.org/10.1002/ptr.2346
  9. Kim YW, Zhao RJ, Park SJ, Lee JR, Cho IJ, Yang CH, Kim SG, Kim SC. Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappaB-dependent iNOS and proinflammatory cytokines production. Br J Pharmacol. 2008 ; 154 : 165-73. https://doi.org/10.1038/bjp.2008.79
  10. Wang MT, Honn KV, Nie D. Cycloxygenases, prostanoids, and tumor progression. Cancer Metastasis Rev. 2007 ; 26 : 525-34. https://doi.org/10.1007/s10555-007-9096-5
  11. Delgado AV, McManus AT, Chambers JP. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuropeptides. 2003 ; 37 : 355-61. https://doi.org/10.1016/j.npep.2003.09.005
  12. Palombella VJ, Rando OJ, Goldberg AL, Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappaB. Cell. 1996 ; 78(5) : 773-85.
  13. Wink DA, Mitchell JB. Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med. 1998 ; 25 : 434-56. https://doi.org/10.1016/S0891-5849(98)00092-6
  14. Kubes P. Inducible nitric oxide synthase: a little bit of good in all of us. Gut. 2000 ; 47 : 6-9. https://doi.org/10.1136/gut.47.1.6
  15. Park YK, Min JY, Lee JH. The effect of Methyl Gallate Isolated from Paeonia suffruticosa on Inflammatory Response in LPS-stimulated RAW 264.7 Cells. Kor J Herbology. 2009 ; 24 : 181-8.
  16. Byun SH, Yang CH, Kim SC. Inhibitory effect of Sctophulariae Radix extract on TNF-$\alpha$, IL$1\beta$, IL-6 and Nitric Oxide production in lipoposaccharide-activated Raw 264.7 cells. Kor J Herbology. 2005 ; 20(2) : 7-16.
  17. 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
  18. Ki SH, Choi MJ, Lee CH, Kim SG. Galpha12 specifically regulates COX-2 induction by sphingosine 1-phosphate. Role for JNK-dependent ubiquitination and degradation of IkappaBalpha. J Biol Chem. 2007 ; 282 : 1938-47. https://doi.org/10.1074/jbc.M606080200
  19. Doi K, Kojima T, Makino M, Kimura Y, Fujimoto Y. Studies on the constituents of the leaves of Morus alba L. Chem Pharm Bull (Tokyo). 2001 ; 49 : 151-3. https://doi.org/10.1248/cpb.49.151
  20. Lee S, Park HS, Notsu Y, Ban HS, Kim YP, Ishihara K, Hirasawa N, Jung SH, Lee YS, Lim SS, Park EH, Shin KH, Seyama T, Hong J, Ohuchi K. Effects of hyperin, isoquercitrin and quercetin on lipopolysaccharide-induced nitrite production in rat peritoneal macrophages. Phytother Res. 2008 ; 22 : 1552-6. https://doi.org/10.1002/ptr.2529
  21. Hamalainen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007 ; 2007 : 45673.
  22. Cho SY, Park SJ, Kwon MJ, Jeong TS, Bok SH, Choi WY, Jeong WI, Ryu SY, Do SH, Lee CS, Song JC, Jeong KS. Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-kappaB pathway in lipopolysaccharide-stimulated macrophage. Mol Cell Biochem. 2003 ; 243 : 153-60. https://doi.org/10.1023/A:1021624520740
  23. Chen YC, Shen SC, Lee WR, Hou WC, Yang LL, Lee TJ. Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages. J Cell Biochem. 2001 ; 82 : 537-48. https://doi.org/10.1002/jcb.1184
  24. Kazlowska K, Hsu T, Hou CC, Yang WC, Tsai GJ. Anti-inflammatory properties of phenolic compounds and crude extract from Porphyra dentata. J Ethnopharmacol. 2010 ; 128 : 123-30. https://doi.org/10.1016/j.jep.2009.12.037
  25. Kim HJ, Jang SI, Kim YJ, Chung HT, Yun YG, Kang TH, Jeong OS, Kim YC. Scopoletin suppresses pro-inflammatory cytokines and PGE2 from LPS-stimulated cell line, RAW 264.7 cells. Fitoterapia. 2004 ; 75 : 261-6. https://doi.org/10.1016/j.fitote.2003.12.021
  26. Fang SH, Hou YC, Chang WC, Hsiu SL, Chao PD, Chiang BL. Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock. Life Sci. 2003 ; 74 : 743-56. https://doi.org/10.1016/j.lfs.2003.07.017

Cited by

  1. Anti-fibrotic Effect of Mori Folium Extract in Hepatic Stellate Cells vol.28, pp.4, 2013, https://doi.org/10.6116/kjh.2013.28.4.49

Acknowledgement

Supported by : 한국연구재단, 대구한의대학교