Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-Inflammatory Activity of Salvia plebeia R. Br. Leaf through Heme Oxygenase-1 Induction in LPS-Stimulated RAW264.7 Macrophages

RAW264.7 대식세포에서 Heme Oxygenase-1 발현을 통한 배암차즈기(Salvia plebeia R. Br.) 잎 추출물의 항염증효과

  • Jeong, Hye-Rim (Dept. of Food Science and Technology, Chungbuk National University) ;
  • Sung, Mi-Sun (Dept. of Food Science and Technology, Chungbuk National University) ;
  • Kim, Yung-Hwa (Dept. of Food Science and Technology, Chungbuk National University) ;
  • Ham, Hyeon-Mi (Dept. of Food Science and Technology, Chungbuk National University) ;
  • Choi, Young-Min (Dept. of Food Science and Technology, Chungbuk National University) ;
  • Lee, Jun-Soo (Dept. of Food Science and Technology, Chungbuk National University)
  • Received : 2012.03.26
  • Accepted : 2012.04.12
  • Published : 2012.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

Salvia plebeia R. Br. (Labiatae), distributed in many countries such as Korea, China, India, Iran, and Australia, is used as a folk remedy for a variety of inflammatory diseases including hepatitis, cough, diarrhea, gonorrhea, menorrhagia, tumors, and hemorrhoids. This study focused on determining the involvement of anti-inflammatory heme oxygenase-1 (HO-1) in the inhibitory activity of an extract of Salvia plebeia R. Br. leaves (SPL) on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. SPL extract at the highest concentration (500 ${\mu}g/mL$) significantly inhibited NO production by approximately 85% and suppressed iNOS protein expression by approximately 90% compared to LPS-stimulated cells. The SPL extract induced the expression of HO-1 in a dose-dependent manner, and blocking HO-1 activity abolished the inhibitory effects of the SPL extract on NO production. These results suggest that an SPL extract has potent anti-inflammatory activity through HO-1 induction in RAW264.7 macrophages.

본 연구에서는 배암차즈기의 항염증 효과를 알아보기 위하여 LPS 자극에 의해 활성화된 RAW264.7 대식세포에서 NO, PGE2 활성, iNOS, COX-2와 HO-1의 발현의 변화를 측정하였다. 연구결과 RAW264.7 대식세포에 LPS를 처리하여 증가되어진 NO의 함량이 배암차즈기 잎 추출물을 처리한 결과 농도 의존적으로 감소되어짐을 확인할 수 있었으며, 또한 배암차즈기 잎 추출물은 NO의 생성에 관여하는 iNOS 단백질 발현과 전사단계의 iNOS의 mRNA 발현을 농도 의존적으로 저해하는 것을 알 수 있었다. 이 결과로 배암차즈기 잎 추출물이 전사단계에서 저해 활성을 나타낸다는 것을 보여주었다. NO 이외의 pro-inflammatory cytokine인 PGE2 또한 배암차즈기 추출물에 의해 농도 의존적으로 감소되었으며 PGE2 생성에 관여하는 효소인 COX-2의 발현 또한 저해하는 활성을 나타내었다. 또한, 배암차즈기 잎 추출물은 HO-1 단백질 발현을 농도 의존적으로 유도하였다. 본 연구 결과 배암차즈기 추출물은 염증을 일으키는 주요인자인 NO, PGE2를 저해하였고, iNOS, COX-2의 발현, iNOS의 mRNA 발현을 억제하여 항염증 효과에 우수한 효과를 나타내었다. 이는 산화적 손상으로부터 세포 보호 방어기작에 관여하는 HO-1의 발현을 증가시킴에 따라 항염증에 우수한 효과를 보였으며 항염증 연구의 기초 자료로 활용될 것으로 예상된다.

Keywords

References

  1. Ismaki P, Punnonen J. 1997. Pro-and anti-inflammatory cytokines in rheumatoid arthritis. Ann Med 29: 449-507.
  2. Nathan C. 1992. Nitric oxide as a secretary product of mammalian cells. FASEB J 6: 3051-3064. https://doi.org/10.1096/fasebj.6.12.1381691
  3. Bogdan C. 2001. Nitric oxide and the immune response. Nat Immunol 2: 2907-2916.
  4. Kim JY, Jung KS, Jeong HG. 2004. Suppressive effects of the kahweol and cafestol on cyclooxygenase-2 expression in macrophages. FEBS Lett 569: 321-326. https://doi.org/10.1016/j.febslet.2004.05.070
  5. Botting RM. 2006. Inhibitors of cyclooxygenases: mechanisms, slectivity and uses. J Physiol Pharmacol 5: S113-124.
  6. Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Lee L, Isakson P. 1994. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci U S A 91: 12013-12017. https://doi.org/10.1073/pnas.91.25.12013
  7. Maines MD. 1997. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 37: 517-554. https://doi.org/10.1146/annurev.pharmtox.37.1.517
  8. Otterbein LE, Choi AM. 2000. Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol 279: 1029-1037. https://doi.org/10.1152/ajplung.2000.279.6.L1029
  9. Schipper HM 2000. Heme oxygenase-1: role in brain aging and neurodegeneration. Exp Gerontol 35: 821-830. https://doi.org/10.1016/S0531-5565(00)00148-0
  10. Nakao A, Otterbein LE, Ovehaus M, Sarady JK, Tsung A, Kimizuka K, Nalesnik MA, Kaizu T, Uchiyama T, Liu F, Murase N, Bauer AJ, Bach FH. 2004. Biliverdin protects the functional integrity of a transplanted syngeneic small bowel. Gastroenterology 127: 595-606. https://doi.org/10.1053/j.gastro.2004.05.059
  11. Ryter SW, Otterbein LE, Morse D, Choi AM. 2002. Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol Cell Biochem 234-235: 249-63. https://doi.org/10.1023/A:1015957026924
  12. Lim JA, Yun BW, Baek SH. 2007. Antioxidative activity and nitrite scavenging ability of methanol extract from Salvia plebeia R. Br. Korea J Medical Crop Sci 15: 183-188.
  13. Shin MK, Kim SK, Lee SK, Yang EY, Lee HO, Baek SH. 2001. Cytotoxicity and antimicrobial effect of the extract of Salvia plebeia. Kor J Pharmacogn 32: 55-60.
  14. Bae IK, Min HY, Han AR, Seo EK, Lee SK. 2005. Suppression of lipopolysaccharide-induced expression of inducible nitric oxide synthase by brazilin in RAW 264.7 macrophage cells. Eur J Pharmacol 513: 237-242. https://doi.org/10.1016/j.ejphar.2005.03.011
  15. Kim JH, Kim DH, Beak SH, Lee HJ, Kim MR, Kwon HJ, Lee CH. 2006. Rengyolone inhibits inducible nitric oxide synthase expression and nitric oxide production by downregulation of NF-${\kappa}B$ and p38 MAP kinase activity in LPSstimulated RAW 264.7 cells. Biochem Pharmacol 71: 1198-1205. https://doi.org/10.1016/j.bcp.2005.12.031
  16. Hseu YC, Wu FY, Wu JJ, Chen JY, Chang WH, Lu FJ, Lai YC, Yang HL. 2005. Anti-inflammatory potential of Antrodia camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-${\kappa}B$ pathway. Int Immunopharmacol 5: 1914-1925. https://doi.org/10.1016/j.intimp.2005.06.013
  17. Hirafuji M, Tsunoda M, Machida T, Hamaue N, Endo T, Miyamoto A, Minami M. 2002. Reduced expressions of inducible nitric oxide synthase and cyclooxygenase-2 in vascular smooth muscle cells of stroke-prone spontaneously hypertensive rats. Life Sci 70: 917-926. https://doi.org/10.1016/S0024-3205(01)01464-3
  18. Jung KH, Ha E, Kin MJ, Won HJ, Zheng LT, Kim HK, Hong SJ, Chung JH, Yim SV. 2007. Suppressive effects of nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by Citrus reticulata extract in RAW 264.6 macrophage cells. Food Chem Toxicol 45: 1545-1550. https://doi.org/10.1016/j.fct.2007.02.017
  19. Weisz A, Cicatiello L, Esumi H. 1996. Regulation of the mouse inducible-type nitric oxide synthase gene promoter by interferon-$\gamma$, bacterial lipopolysaccharide, and $N^G$-monomethyl-L-arginine. Biochem J 316: 209-215. https://doi.org/10.1042/bj3160209
  20. Kamatou GPP, Viljoen AM, Gono-Bwalya AB, Van Zyl RL, Van Vuuren SF, Lourens ACU, Baser KHC, Demirci B, Lindsey KL, Van Staden J, Steenkamp P. 2005. The in vitro pharmacological activities and a chemical investigation of three South African Salvia species. J Ethnopharmacol 102: 382-390. https://doi.org/10.1016/j.jep.2005.06.034
  21. Qu XJ, Xia X, Wang YS, Song MJ, Liu LL, Xie YY, Cheng YN, Liu XJ, Qiu LL, Xiang L, Gao JJ, Zhang XF, Cui SX. 2009. Protective effects of Salvia plebeia compound homoplantaginin on hepatocyte injury. Food Chem Toxicol 47: 1710-1715. https://doi.org/10.1016/j.fct.2009.04.032
  22. Harris SG, Padilla J, Koumas L, Ray D, Phipps RP. 2002. Prostaglandins as modulators of immunity. Trends Immunol 23: 144-150. https://doi.org/10.1016/S1471-4906(01)02154-8
  23. Hinz B, Kraus V, Pahl A, Brune K. 2000. Salicylate metabolites inhibit cyclooxygenase-2 dependent prostaglandin E2 synthesis in murine macrophages. Biochem Biophys Res Commun 274: 197-202. https://doi.org/10.1006/bbrc.2000.3123
  24. Pang L, Hoult JRS. 1997. Repression of inducible nitric oxide synthase and cyclooxygenase-2 by prostaglandin E2 and other cyclic AMP stimulants in J774 macrophages. Biochem Pharmacol 53: 493-500. https://doi.org/10.1016/S0006-2952(96)00737-X
  25. Garcia X, Stein F. 2006. Nitric oxide. Semin Pediatr Infect Dis 17: 55-57. https://doi.org/10.1053/j.spid.2006.04.002
  26. Lee HN, Lim DY, Lim SS, Kim JD, Yoon Park JH. 2011. Anti-inflammatory effect of ethanol extract from Eupatorium japonicum. Korean J Food Sci Technol 43: 65-71. https://doi.org/10.9721/KJFST.2011.43.1.065
  27. Lee DS, Jeong GS, Li B, Park H, Kim YC. 2010. Anti-inflammatory effects of sulfuretin from Rhus verniciflua stokes via the induction of heme oxygenase-1 expression in murine macrophages. Int Immunophacol 10: 850-858. https://doi.org/10.1016/j.intimp.2010.04.019
  28. Jung JY, Lee JR, Byun SH, Jung JW, Kim YH, Kim SC. 2010. Inhibition effect of dioscorea bulbifera methanol extract on pro-inflammatory mediator in vitro and in vivo. Korea J Oriental Physiol Pathol 24: 310-318.
  29. Kim CS, Kawada T, Kim BS, Han IS, Choe SY, Kurata T, Yu R. 2003. Capsaincin exhibition anti-inflammatory property by inhibiting IkB-$\alpha$ degradation in LPS-stimulated peritoneal macrophages. Cell Signal 15: 299-306. https://doi.org/10.1016/S0898-6568(02)00086-4
  30. Li L, Grenard P, Nhieu JT, Julien B, Mallat A, Habib A, Lotersztajn S. 2003. Heme oxygenase-1 is an antifibrogenic protein in human hepatic myofibroblasts. Gastroenterology 125: 460-468. https://doi.org/10.1016/S0016-5085(03)00906-5
  31. Tamion F, Richard V, Bonmarchand G, Leroy J, Lebreton JP, Thuillez C. 2001. Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic shock. Am J Respir Crit Care Med 164: 1933-1938. https://doi.org/10.1164/ajrccm.164.10.2010074
  32. Park SY, Kim YH, Kim EY, Ryu EY, Lee SJ. 2010. Heme oxygenase-1 signals are involved in preferential inhibition of pro-inflammatory cytokine release by surfactin in cell activated with Porphyromonas gingivalis lipopolysaccharide. Chem Biol Interact 188: 437-445. https://doi.org/10.1016/j.cbi.2010.09.007

Cited by

  1. Antioxidant and Physicochemical Changes in Salvia plebeia R. Br. after Hot-air Drying and Blanching vol.43, pp.6, 2014, https://doi.org/10.3746/jkfn.2014.43.6.893
  2. Antioxidative Activities and Qualitative Characteristics of Substitute Tea using Salvia plebeia R. Br. vol.31, pp.1, 2015, https://doi.org/10.9724/kfcs.2015.31.1.041
  3. Active Ingredients and Antioxidant Activities of Salvia plebeia R. Br. According to Pretreatment Conditions vol.43, pp.12, 2014, https://doi.org/10.3746/jkfn.2014.43.12.1948
  4. Immuno-Modulatory Activities of Polysaccharides separated from Chrysanthemum zawadskii var. latilobum in Macrophage Cells vol.29, pp.3, 2016, https://doi.org/10.9799/ksfan.2016.29.3.431
  5. Antiadipogenic Effects of Salvia plebeia R. Br. Extracts by Extraction Conditions in 3T3-L1 Preadipocytes vol.23, pp.3, 2015, https://doi.org/10.7783/KJMCS.2015.23.3.245
  6. Anti-Inflammatory Effect of Grateloupia imbricata Holmes Ethanol Extract on LPS-Induced RAW 264.7 Cells vol.45, pp.2, 2016, https://doi.org/10.3746/jkfn.2016.45.2.181
  7. Analytical Method for the Validation of Hispidulin as a Marker Compound for the Standardization of Salvia plebeia R. Br. Extracts as a Functional Ingredient vol.24, pp.4, 2016, https://doi.org/10.7783/KJMCS.2016.24.4.271
  8. Anti-inflammatory Activity of the Undaria pinnatifida Water Extract vol.55, pp.4, 2012, https://doi.org/10.3839/jabc.2012.035
  9. Anti-Inflammatory Effect of Chondrus nipponicus Yendo Ethanol Extract on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells vol.45, pp.2, 2016, https://doi.org/10.3746/jkfn.2016.45.2.194
  10. Anti-Inflammatory Effect of Alginate Oligosaccharides Produced by an Alginate-Degrading Enzyme from Shewanella oneidensis PKA1008 on LPS-Induced RAW 264.7 Cells vol.48, pp.6, 2015, https://doi.org/10.5657/KFAS.2015.0888
  11. Effect of Salvia plebeia Water Extract on Antioxidant Activity and Lipid Composition of Rats Fed a High Fat-High Cholesterol Diet vol.27, pp.2, 2016, https://doi.org/10.7856/kjcls.2016.27.2.233
  12. Anti-Inflammatory Effect of Ethanol Extract from Grateloupia elliptica Holmes on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells and Mice Ears vol.44, pp.8, 2015, https://doi.org/10.3746/jkfn.2015.44.8.1128
  13. Antiobesity Effects of Salvia plebeia R. Br. Extract in High-Fat Diet-Induced Obese Mice vol.19, pp.11, 2016, https://doi.org/10.1089/jmf.2016.3763
  14. Evaluation of Antioxidant, Anti-Inflammatory, Antithrombotic, and Antiobesity Activities in Cultured Edible Plants to Increase Farm Income vol.28, pp.1, 2017, https://doi.org/10.7856/kjcls.2017.28.1.29
  15. Antioxidant and Anti-inflammatory Activity of Medicinal Herbs Composites vol.49, pp.5, 2015, https://doi.org/10.14397/jals.2015.49.5.279
  16. Inhibitory Activity of Sargassum hemiphyllum Ethanol Extract on Inflammatory Response in LPS-induced RAW 264.7 Cells and Mouse Model vol.32, pp.4, 2017, https://doi.org/10.7841/ksbbj.2017.32.4.319
  17. NF-κB와 MAPKs 활성 저해를 통한 미야베 모자반(Sargassum miyabei Yendo) 에탄올 추출물의 항염증 활성 vol.44, pp.4, 2016, https://doi.org/10.4014/mbl.1607.07001
  18. 미세아교세포에서 알츠하이머형 치매 치료 처방인 뇌명산(腦明散)의 효능 및 기전연구 vol.25, pp.4, 2012, https://doi.org/10.14374/hfs.2017.25.4.471
  19. LPS로 유도된 RAW 264.7 세포에 대한 흑색 방울토마토 주스의 항염증 효과 vol.28, pp.5, 2012, https://doi.org/10.5352/jls.2018.28.5.569
  20. Physicochemical and biological properties of Gochujang in the presence of fermented apple products vol.26, pp.2, 2012, https://doi.org/10.11002/kjfp.2019.26.2.201
  21. 전통적인 발효 방법으로 제조된 참외식초의 기능적 특성 vol.29, pp.3, 2012, https://doi.org/10.5352/jls.2019.29.3.345
  22. 다시마 물 추출액과 발효액의 항산화 및 항염증 활성 vol.29, pp.5, 2012, https://doi.org/10.5352/jls.2019.29.5.596
  23. The Anti-Inflammatory Effect from Lipopolysaccharide-Stimulated RAW 264.7 of Extracts of Hydrangea serrata Seringe vol.50, pp.3, 2012, https://doi.org/10.3746/jkfn.2021.50.3.236
  24. Anti-Inflammatory Effects of 6,7-Dihydroxy-4-Methylcoumarin on LPS-Stimulated Macrophage Phosphorylation in MAPK Signaling Pathways vol.16, pp.5, 2012, https://doi.org/10.1177/1934578x211020970
  25. Antioxidant Effect of Raphanus sativus L. through the Suppression of Reactive Oxygen Species Production vol.50, pp.11, 2021, https://doi.org/10.3746/jkfn.2021.50.11.1145
  26. Anti-inflammatory Effect of Distylium racemosum leaf Biorenovate Extract in LPS-stimulated RAW 264.7 Macrophages Cells vol.64, pp.4, 2021, https://doi.org/10.3839/jabc.2021.051