Articular Cartilage Protective Effects of Kangwhaldoche-tang(Qianghuodaozhi-tang) Aqueous Extracts on the Adjuvant-induced Rat Rheumatoid Arthritis

강활도체탕(羌活導滯湯) 물 추출물의 Adjuvant 유발 류마티스 관절염 랫트에 대한 관절연골 보호효과

  • Kwon, O-Gon ;
  • An, Hee-Duk
  • 권오곤 ;
  • 안희덕
  • Published : 2013.04.30


Objectives : This study was conducted to determine whether or not Kangwhaldoche-tang(Qianghuodaozhi-tang) (KDT) aqueous extracts can protect articular cartilage losses on the Freund's complete adjuvant(FCA)-induced rat rheumatoid arthritis. Methods : 520, 260 or 130 mg/kg of KDT were orally administered once a day for 14 days from 14 days after FCA treatments, and 15 mg/kg of dexamethasone was intraperitoneally administered as reference drug in this experiment. Changes on the body weight, knee circumferences, gross arthritis score, inflammatory tissue prostaglandin(PG) $E_2$ levels were monitored with cartilage collagen components and glucosaminoglycans(GAGs) compositions - chondroitin sulphate, heparin sulphate and hyaluronic acid in the present study. Results : As results of FCA treatment, classic rheumatoid arthritis featuring dramatic decreases of the body weights, cartilage collagen and GAGs contents with increases of the knee circumferences, gross arthritis scores and inflammatory tissue $PGE_2$ levels, were demonstrated in the present study. However, these changes from FCA - induced rheumatoid arthritis were clearly inhibited by treatment of dexamethasone and all three different dosages of KDT. Although overall anti-inflammatory effects of KDT 520 mg/kg were lowered than those of dexamethasone 15 mg/kg treated rats, KDT 520 mg/kg showed more favorable preserve effects on the cartilage GAGs and KDT 260 mg/kg treated rats showed similar preserve effects as compared with dexamethasone 15 mg/kg in this experiment. Conclusions : The present results supported that over 75 mg/kg of KDT showed favorable anti-arthritic effects on the FCA-induced arthritis mediated by suppression of $PGE_2$, representative inflammatory mediator, and may help improve rheumatoid arthritis.


Kangwhaldoche-tang(Qianghuodaozhi-tang);Adjuvant;Rheumatoid Arthritis


  1. Homer KA, Denbow L, Beighton D. Spectrophotometric method for the assay of glycosaminoglycans and glycosaminoglycan-depolymerizing enzymes. Anal Biochem. 1993;214:435-41.
  2. Levene A. Pathological factors influencing excision of tumours in the head and neck. Part I. Clin Otalary. 1981;6:145-51.
  3. Ludbrook J. Update: microcomputer statistics packages. A personal view. Clin Exp Pharmacol Physiol. 1997;24:294-6.
  4. Chi YM, Nakamura M, Zhao AY, Yoshizawa T, Yan WM, Hashimoto F, Kinjo J, Nohara T, Sakurada S. Anti-inflammatory activity of 4, 4'-dihydroxy-alpha-truxillic acid. Biol Pharm Bull. 2006;29:489-93.
  5. Zaringhalam J, Manaheji H, Mghsoodi N, Farokhi B, Mirzaiee V. Spinal mu-opioid receptor expression and hyperalgesia with dexamethasone in chronic adjuvant-induced arthritis in rats. Clin Exp Pharmacol Physiol. 2008;35:1309-15.
  6. Yu F, Yu F, Li R, Wang R. Inhibitory effects of the Gentiana macrophylla(Gentianaceae) extract on rheumatoid arthritis of rats. J Ethnopharmacol. 2004;95:77-81.
  7. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J. 1998;12:1063-73.
  8. Fogel-Petrovic M, Long JA, Knight DA, Thompson PJ, Upham JW. Activated human dendritic cells express inducible cyclo-oxygenase and synthesize prostaglandin E2 but not prostaglandin D2. Immunol Cell Biol. 2004;82:47-54.
  9. Poole AR, Witter J, Roberts N, Piccolo F, Brandt R, Paquin J, Baron M. Inflammation and cartilage metabolism in rheumatoid arthritis. Studies of the blood markers hyaluronic acid, orosomucoid, and keratan sulfate. Arthritis Rheum. 1990;33:790-9.
  10. Thonar EJ, Lenz ME, Klintworth GK, Caterson B, Pachman LM, Glickman P, Katz R, Huff J, Kuettner KE. Quantification of keratan sulfate in blood as a marker of cartilage catabolism. Arthritis Rheum. 1985;28:1367-76.
  11. Emlen W, Niebur J, Flanders G, Rutledge J. Measurement of serum hyaluronic acid in patients with rheumatoid arthritis: correlation with disease activity. J Rheumatol. 1996;23:974-8.
  12. Ramprasath VR, Shanthi P, Sachdanandam P. Therapeutic effects of Semecarpus anacardium Linn. nut milk extract on the changes associated with collagen and glycosaminoglycan metabolism in adjuvant arthritic Wistarrats. Chem Biol Interact. 2006;162:43-52.
  13. Niikura K, Nakajima S, Takano M, Yamazaki H. FR177995, a novel vacuolar ATPase inhibitor, exerts not only an inhibitory effect on bone destruction but also anti-immunoinflammatory effects in adjuvant-induced arthritic rats. Bone. 2007;40:888-94.
  14. Mythilypriya R, Shanthi P, Sachdanandam P. Efficacy of Siddha formulation Kalpaamruthaa in ameliorating joint destruction in rheumatoid arthritis in rats. Chem Biol Interact. 2008;176:243-51.
  15. Okumura T, Murata Y, Taniguchi K, Murase A, Nii A. Effects of the selective EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat adjuvant-induced arthritis. J Pharm Pharmacol. 2008;60:723-30.
  16. Hatori M, Ohki K, Hirano S, Yang XP, Kuboki H, Abe C. Effects of a casein hydrolysate prepared from Aspergillus oryzae protease on adjuvant arthritis in rats. Biosci Biotechnol Biochem. 2008;72:1983-91.
  17. Yoshikawa T, Tanaka H, Kondo M. Effect of vitamin E on adjuvant arthritis in rats. Biochem Med. 1983;29:227-34.
  18. Yoshikawa T, Tanaka H, Kondo M. Lipid peroxidation in rat adjuvant arthritis and its inhibition by indomethacin. J Appl Biochem. 1983;5:382-7.
  19. Kang SY, Yoon SY, Roh DH, Jeon MJ, Seo HS, Uh DK, Kwon YB, Kim HW, Han HJ, Lee HJ, Lee JH. The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis models. J Pharm Pharmacol. 2008;60:1347-54.
  20. Department of Health, Education, and Welfare Publication. National Institute of Health. 1985:85-23.
  21. Kim HD, Cho HR, Moon SB, Shin HD, Yang KJ, Park BR, Jang HJ, Lim LS, Lee HS, Ku SK. Effect of Exopolymers from Aureobasidumpullulans on formalin-induced chronic paw inflammation in mice. J Microbiol Biotechnol. 2006;16:1954-60.
  22. Bamgbose SO, Noamesi BK. Studies on cryptolepine. II: Inhibition of carrageenan induced oedema by cryptolepine. Planta Med. 1981;41:392-6.
  23. Chen Q. Method of Chinese Medicine Pharmacology. Beijing:Chinese People Health Press. 1996.
  24. Leach AA. Notes on a modification of the Neuman and Logan method for the determination of the hydroxyproline. Biochem J. 1960;74:70-1.
  25. Neuman RE, Logan MA. The determination of collagen and elastin in tissues. J Biol Chem. 1950;186:549-56.
  26. Neuman RE, Logan MA. The determination of hydroxyproline. J Biol Chem. 1950;184:299-306.
  27. Seed MP, Gardner CR. The modulation of intra-articular inflammation, cartilage matrix and bone loss in mono-articular arthritis induced by heat-killed Mycobacterium tuberculosis. Inflammopharmacology. 2005;12:551-67.
  28. Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358:903-11.
  29. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, Dell JO, Winthrop KL, Beukelman T, Bridges Jr. SL, Chatham WW, Paulus HE, Almazor MS, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae SM, Mudano AS, Patkar NM, Saag KG. 2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis. Arthritis care Res. 2012;64(5):625-39.
  30. Blom M, Kievit W, Fransen J, et al. The reason for discontinuation of the first tumor necrosis factor(TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis. J Rheumatol. 2009;36:2171-7.
  31. 李梴. 新對譯 編註醫學入門. 서울:법인문화사. 2009:1828.
  32. 전동주, 차윤엽, 이은. 대황추출물의 염증반응 제어효과. 한방재활의학과학회지. 2011;21(1):35-46.
  33. 김창민, 박용기. 강활의 RAW264.7 세포에서 LPS에 의해 유도되는 염증물질 생성에 대한 효과. 대한본초학회지. 2009;24(1):169-78.
  34. 이종한, 김윤상, 임은미. 독활 물 추출물이 대식세포 면역 활성에 미치는 영향. 대한한의학회지. 2011;32(1):175-84.
  35. Zhao XX, Peng C, Zhang H, Qin LP. Sinomenium acutum: A review of chemistry, pharmacology, pharmacokinetics, and clinical use. Pharm Biol. 2012;50:1053-61.
  36. Mahat B, Chae JW, Baek IH, Song GY, Song JS, Cho SK, Kwon KI. Physicochemical characterization and toxicity of decursin and their derivatives from Angelicagigas. Biol Pharm Bull. 2012;35:1084-90.
  37. Kawaguchi K, Maruyama H, Hasunuma R, Kumazawa Y. Suppression of inflammatory responses after onset of collagen-induced arthritis in mice by oral administration of the Citrus flavanone naringin. Immunopharmacol Immunotoxicol. 2011;33:723-9.
  38. Reddy GK, Dhar SC. Metabolism of glycosaminoglycans in tissues of adjuvant arthritic rat. Mol Cell Biochem. 1991;106:117-24.