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

Inhibition of Inflammatory-cytokines Production and Prostaglandin E2 Activity by Puerariae Radix Extracts

갈근 추출물에 의한 염증성 Cytokine 생성 억제 및 Prostaglandin E2 활성 저해에 관한 연구

  • 김시나 ((주)KMSI 부설 한국의과학연구소) ;
  • 김희석 ((주)KMSI 부설 한국의과학연구소) ;
  • 남경숙 ((주)KMSI 부설 한국의과학연구소) ;
  • 황성완 ((주)KMSI 부설 한국의과학연구소) ;
  • 황성연 ((주)KMSI 부설 한국의과학연구소)
  • Published : 2006.01.01
Download PDF
⟨ Previous Next ⟩

Abstract

The ethanol extracts of Puerariae Radix inhibited cyclooxygenase-2 (COX-2) activity in bone marrow derived mast cells (BMMC). COX-2 is responsible for the production of large amounts of proinflammatory prostaglandins (PGs) at the inflammatory site. We have investigated the anti-inflammatory effect of ethyl acetate fraction from $70\%$ ethanol extract of Puerariae Radix (EPR), and attempted acetic acid induced writhing to verify the analgesic effect. Inflammation was induced by interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a), $inteferon-\gamma$ $(IFN-\gamma)$ and lipopolysaccharide (LPS). EPR showed strong inhibitory efficacy against cytokine-induced proteoglycan degradation, prostaglandin $E_2\;(PGE_2)$ production, nitric oxide (NO) production, and matrix-metalloproteinases (MMPs) expression in mouse macrophage and rabbit articular chondrocyte. In the writhing test, EPR $(200\~400\;mg/kg)$ exhibited a dose-dependent inhibition of writhing. The results indicate that EPR have anti-inflammatory and analgesic activities, and could be a good herbal medicine candidate for treating of osteoarthritis (OA).

갈근(Puerariae Radix)의 $70\%$ ethanol 추출물 중 ethyl acetate 분획물(EPR)은 염증성 cytokine을 처리한 마우스 대식세포 및 토기 연골조직세포에서 염증의 발현과 관련된 NO 생성 저해효과를 보였고, 관절조직의 주요 성분 중 하나인 proteoglycan의 분해 억제효과와 관절조직 분해효소인 MMP-9의 활성이 억제되었다. 또한, 통증유발물질인 프로스타글란딘의 유의성 있는 감소를 보여 통증억제 효과가 있음을 확인하였을 뿐만 아니라 초산 유발 진통 효과테스트인 동물 모델에서도 효과적으로 통증을 억제함을 확인하였다. 즉, 갈근의 $70\%$ ethanol 추출물 중 ethyl acetate 분획물(EPR)은 독성의 문제뿐만 아니라, 소염, 진통 효과 및 연골 조직세포의 분해를 억제하는 다양한 효과를 나타내는 장점을 지니고 있어 관절염 치료제의 훌륭한 후보약재가 될 것으로 기대된다.

Keywords

References

  1. 박용범. 2002. 골관절염의 내과적 치료. 대한내과학회지 63: S436-S443
  2. Isselbcher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL. 1994. Harrison's principles of internal medicine. 13th ed. McGraw-Hill Inc, New York. p 1543
  3. Flower RJ. 1999. New directions in cyclooxygenase re-search and their implications for NSAID-gastripathy. Ital J Gastroenterol 28(4): 23-27
  4. Nam KW, Je KG, Lee JG, Han HJ, Kang SK, Mar WC. 2003. Inhibition of COX-2 activity and proinflammatory cytokines (TNF-$\alpha$ and IL-1$\beta$) production by water-sol-uble sub-fractionated parts from bee (Apis mellifera) venom. Arch Pharm Res 26: 383-388 https://doi.org/10.1007/BF02976695
  5. Badger AM, Cook MN, Swift BA, Newmantraa TM, Gowen M, Lark M. 1999. Inhibition of interleukin-1 induced pro-teoglycan degradation and nitric oxide production in bovine articular cartilage/chondrocyte cultures by the natural product, hymenialdisine. J Pharmacol Exp Ther 290: 587-593
  6. Gowen M, Wood DD, Ihrie EJ, Russel RGG. 1984. Stim-ulation by human IL-1 of cartilage breakdown and pro-duction of collagenase and proteoglycanase by human chon-drocytes but not by human osteoblast in vitro. Biochem Biophys Acta 797: 186-193 https://doi.org/10.1016/0304-4165(84)90121-1
  7. Westacott CI, Sharif M. 1996. Cytokines in osteoarthritis: Mediators or markers of joint destruction. Semin Arthritis Rheum 25: 254-272 https://doi.org/10.1016/S0049-0172(96)80036-9
  8. Lee SH, Seo GS, Sohn DH. 2004. Inhibition of lipo-polysaccharided-induced expression of inducible nitric oxide synthase by butein in RAW 264.7 cells. Biochem Biophys Res Commun 323: 125-132 https://doi.org/10.1016/j.bbrc.2004.08.063
  9. Park BJ, Cho MG, Kim KG, Lee SK, Lee CS, An GH, Mar WC. 1999. Effect of natural product on the inhibition of lipopolysacchride-induced nitric oxide synthase activity in RAQ 264.7 cell culture system. Natural Product Sciences 5(3): 113-120
  10. Kim HT, Ahn JS, Jeong IH. 1996. Subacute toxicity of SKI306X, an anti-inflammatory herbal extract, in rats. J Applied Pharmacol 1: 19-31
  11. Sandy JD, Brwon HLG, Lowther DA. 1978. Degradation of proteoglycan in acticular cartilage. Biochem Biophys Acta 543: 539-544
  12. Moon YH, Go JJ, Park JY. 1999. The anti-inflammatory and analgesic activities of Gumiganghwaltang. Kor J Pharmacogn 30: 18-24
  13. Ha HK, Lee JH, Kim CS. 2000. Extracts of Rheum un-dulatum L. inhibits COX-2 activities in lipopolysaccharide- stimulated raw 264.7 cells. J Applied Pharmacol 8: 73-77
  14. Kim JY, Park SW. 2004. Effect of geraniol on the prolifer-ation of L1210 cells and ICR mouse macrophages, and the activities of superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) activities. Yakhak Hoeji 48: 309-316
  15. Lee SJ. 1980. Bonchokangmok. Komunsa, Seoul. Vol 18, p 537
  16. Hur J. 1984. Donguibokam. Mansandong, Seoul. Vol 3, p 726
  17. Zeng GY, Cheng YS, Fan LL, Zhou YP, Zhang LY. 1982. Pharmacologic studies on Radix puerariae: effects of pu-erariae flavones on coronary circulation, cardiac hemo-dynamics and myocardial metabolism in dogs. Chinese Med J 95: 145-150
  18. Huh LH, Kim HC, Lee SJ. 1987. Studies on anti-inflam- matory activity and its mechanism of daidzein. J Phar-maceut Soc Kor 31: 164-163
  19. Oh MJ, Lee KS, Son HY, Kim SY. 1990. Antioxidative components of Pueraria root. J Kor Soc Food Sci Tech 22: 793-795
  20. Lee CH, Han SH, Min SG. 1995. The effects of Puerariae radix actechins administration on liver function in carbon tetrachloride-treated rats. J Korean Soc Food Nurt 24: 713-719
  21. Lee JS, Kim ES, Kim SW. 1999. Effects of extract of Pueraria radix on lipid peroxidation in ethanol-admin-istered rats. J Korean Soc Food Sci Nurt 28: 901-906
  22. Lin RC, Guthrie S, Xie CY, Mai K, Lee DY, Lumeng L, Li TK. 1996. Isoflavone compounds extracted from Pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism. Alcohol Clin Exp Ress 20: 659-663 https://doi.org/10.1111/j.1530-0277.1996.tb01668.x
  23. Park KH, Koh DS, Lim YH. 2001. Anti-asthmatic com-pound with leukotriene D4 antagonism isolated from Puerariae radix. J Korean Soc Agric Chem Biotechnol 44: 38-39
  24. 심상용. 1983. 약이 되는 자연식. 창조사, 서울. p 142
  25. Moon TC, Chung KC, Son KH, Kim HP, Kang SS, Chang HW. 1998. Screening of cyclooxygenase-2 (COX-2) inhib-itors from natural products. Yakhak Hoeji 42: 214-219
  26. Bors W, Heller W, Michel C, Saran M. 1990. Flavonoids as antioxidants: Determinaton of radical-scavenging effi-ciencies. Methods Enzymol 186: 343-355 https://doi.org/10.1016/0076-6879(90)86128-I
  27. Liang Y, Huang Y, Tsai S, Lin-Shiau S, Chen C, Lin J. 1999. Suppression of inducible cyclooxygenase and induc-ible nitric oxide synthase by apigenin andrelated flavonoids in mouse macrophages. Carcinogenesis 20: 1645-1652 https://doi.org/10.1093/carcin/20.8.1645
  28. Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. 1999. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure-activity relationships. Biochemical Pharmacol-ogy 58: 759-765 https://doi.org/10.1016/S0006-2952(99)00160-4
  29. Kobayashi T, Nakata T, Kuzumaki T. 2002. Effect of fla-vonoids on cell cycle progression in prostate cancer cells. Cancer Letters 176: 17-23 https://doi.org/10.1016/S0304-3835(01)00738-8
  30. Husain SR, Cillard J, Cillard P. 1987. Hydroxyl radical scavenging activity of flavonoids. Phytochemistry 26: 2489-2491 https://doi.org/10.1016/S0031-9422(00)83860-1
  31. Lee OH. 2004. Effects of supplementation of Puerariae radix ethanol extract on the antioxidative defense system in rats. J Korean Soc Food Sci Nutr 37: 872-880
  32. Elliott S, Cawston T. 2002. The clinical potential of matrix metalloproteinase inhibitors in rheumatic disorders. Drug Aging 18: 87-99 https://doi.org/10.2165/00002512-200118020-00002
  33. Farrell AJ, Blake DR, Palmer RM, Moncada J. 1992. In-creased concentrations of nitric synovial fluid and serum samples suggest increased nitric oxide synthesis in rheu-matic diseases. Ann Rheum Dis 51: 1219-1222 https://doi.org/10.1136/ard.51.11.1219

Cited by

  1. Effect of the root extract of Pueraria thunbergiana Bentham on high fat/high sucrose diet and single low-dose streptozotocin-induced diabetic mice vol.29, pp.5, 2014, https://doi.org/10.6116/kjh.2014.29.5.75
  2. 인체 모유두세포의 증식에 미치는 갈근 에탄올추출물의 효과 vol.31, pp.3, 2006, https://doi.org/10.15188/kjopp.2017.06.31.3.167
  3. 인체 모유두세포의 증식에 미치는 갈근 에탄올추출물의 효과 vol.31, pp.3, 2006, https://doi.org/10.15188/kjopp.2017.06.31.3.167
  4. 미세먼지로 유도된 기관지염증에 다시마가 함유된 복합물의 효과 vol.34, pp.5, 2006, https://doi.org/10.15188/kjopp.2020.10.34.5.245