Suppressing Effects of Sowhalrack-dan(Xiǎohuóluò-dān) on Freund's Complete Adjuvant Induced Arthritic Rats

Adjuvant 유발(誘發) 류마티스 관절염(關節炎)에 대한 소활락단(小活絡丹)의 억제(抑制) 효과(效果)

  • Yun, Sun-Mo (Dept. of Oriental Rehabilitation Medicine, Oriental Medical College, Daeguhaany University) ;
  • Jeong, Man-Jin (Dept. of Oriental Rehabilitation Medicine, Oriental Medical College, Daeguhaany University) ;
  • Kwon, O-Gon (Dept. of Oriental Rehabilitation Medicine, Oriental Medical College, Daeguhaany University) ;
  • Woo, Chang-Hoon (Dept. of Oriental Rehabilitation Medicine, Oriental Medical College, Daeguhaany University) ;
  • An, Hee-Duk (Dept. of Oriental Rehabilitation Medicine, Oriental Medical College, Daeguhaany University)
  • 윤순모 (대구한의대학교 한의과대학 한방재활의학과 교실) ;
  • 정만진 (대구한의대학교 한의과대학 한방재활의학과 교실) ;
  • 권오곤 (대구한의대학교 한의과대학 한방재활의학과 교실) ;
  • 우창훈 (대구한의대학교 한의과대학 한방재활의학과 교실) ;
  • 안희덕 (대구한의대학교 한의과대학 한방재활의학과 교실)
  • Received : 2010.12.15
  • Accepted : 2011.01.10
  • Published : 2011.01.30


Objectives : The object of this study is to observe the favorable anti arthritic effects of Sowhalrack-dan($Xi\check{a}ohu\acute{o}lu\grave{o}-d\bar{a}n$)(SWRD), which has been traditionally used in Korean medicine to treat rheumatoid arthritis on Freund's complete adjuvant(FCA) induced arthritic Wistar rats. Methods : Rheumatoid arthritis was induced by intradermal injection of FCA(10 mg in 1 ml paraffin oil 0.1 ml/rats). Each of 8 rats showing regular ankle circumferences per group were selected in 14 days after FCA treatment to confirm the induction of rheumatoid arthritis. 300, 150 or 75 mg/kg of SWRD was orally administered once a day for 14 days from 14 days after FCA treatments. Dexamethasone was intraperitoneally administered 15 mg/kg, once a day for 14 days from 14 days after FCA treatments. Rats were sacrificed after 14 days of continuous oral treatment of SWRD or intraperitoneal administration of dexamethasone, and changes were observed; the body weight, knee circumferences, gross arthritis score, inflammatory tissue $prostaglandin(PG)E_2$ levels and cartilage collagen, glucosaminoglycans compositions - chondroitin sulphate, heparin sulphate and hyaluronic acid in the present study. Results : As results of FCA treatment, classic rheumatoid arthritis featuring dramatical decreases on the body weights, cartilage collagen contents and bone glucosaminoglycans - chondroitin sulphate, heparin sulphate and hyaluronic acid contents. Also, it increases the knee circumferences, gross arthritis scores and inflammatory tissue $PGE_2$ levels. However, these changes from FCA induced rheumatoid arthritis were clearly reduced due to the dexamethasone and both two different dosages of SWRD, 300 and 150 mg/kg in the present study. Although FCA induced arthritis were more favorably inhibited by treatment of dexamethasone 15 mg/kg compared to SWRD 300 mg/kg, marked decreases of body weights were detected in dexamethasone 15 mg/kg treated rats. Conclusions : The results obtained in this study suggest that over 150 mg/kg of SWRD showed favorable anti-arthritic effects on the FCA induced arthritis mediated by suppression of $PGE_2$. However, detailed mechanism studies are needed with the screening of the biological active compounds in SWRD. Although FCA induced arthritis were more favorably inhibited by treatment of dexamethasone 15 mg/kg compared to SWRD 300 mg/kg, marked decreases of body weights were detected in dexamethasone 15 mg/kg treated rats, in the present study.


  1. 곽중문, 오민석, 박종오, 김동희. 소풍활혈탕가미방이 collagen으로 유발된 생쥐의 관절염 억제에 관한 연구. 동의생리병리학회지. 2002;16:810-7.
  2. Gough AKS, Lilley J, Eyre S. Generalized bone loss in patients with early rheumatoid arthritis. Lancet. 1994;334:23-7.
  3. Zhou H, Wu D, Ma L. Clinical analyses of severe harmful effects with low dose methotrexate in short time. Chinese J Rheumatol. 2002;4:135-7.
  4. Ye S, Sun L. Advance of materia medica for rheumatoid arthritis. Chinese J Rheumatol. 2000;2:135-7.
  5. 鞠潤範, 金相贊, 朴宣東, 朴性奎, 徐富一 외 7명. 方劑學. 서울:圖書出版 永林社. 2008:448-50.
  6. 김호연. 류머티스 관절염의 병인. 대한의학협회지. 1992;35:1198.
  7. 白洪龍. 常見病症辨證診治槪要. 雲南省:雲南人民衛生出版社. 1984:382-5.
  8. 朴病昆. 增補韓方臨床40年. 서울:大光文化社. 1989:343.
  9. 陳師文. 和劑局方. 서울:醫聖堂. 1985:26.
  10. Shi H, Zhou C, Li Y, Wang G, Sun Y. Anti inflammatory effect of aconitines. Zhongguo Zhong Yao Za Zhi. 1990;15:174-7, 192.
  11. Moussaieff A, Shein NA, Tsenter J, Grigoriadis S, Simeonidou C, Alexandrovich AG, Trembovler V, Ben Neriah Y, Schmitz ML, Fiebich BL, Munoz E et al. Incensole acetate: a novel neuroprotective agent isolated from Boswellia carterii. J Cereb Blood Flow Metab. 2008; 28:1341-52.
  12. Atta AH, Alkofahi A. Anti nociceptive and anti inflammatory effects of some Jordanian medicinal plant extracts. J Ethnopharmacol. 1998;60:117-24.
  13. Tipton DA, Lyle B, Babich H, Dabbous MKh. In vitro cytotoxic and anti inflammatory effects of myrrh oil on human gingival fibroblasts and epithelial cells. Toxicol In Vitro. 2003;17:301-10.
  14. Reddy GK, Dhar sc. Metabolism of glycosaminoglycans in tissues of adjuvant arthritic rat. Mol Cell Biochem. 1991;106:117-24.
  15. 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.
  16. 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 Wistar rats. Chem Biol Interact. 2006;162:43-52.
  17. 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.
  18. 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.
  19. Okumura T, Murata Y, Taniguchi K, Murase A, Nii A. Effects of the selective EP4 antagonist, CJ023,423 on chronic inflammation and bone destruction in rat adjuvant induced arthritis. J Pharm Pharmacol. 2008;60:723-30.
  20. 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.
  21. Yoshikawa T, Tanaka H, Kondo M. Lipid peroxidation in rat adjuvant arthritis and its inhibition by indomethacin. J Appl Biochem. 1983;5:382-7.
  22. Yoshikawa T, Tanaka H, Kondo M. Effect of vitamin E on adjuvant arthritis in rats. Biochem Med. 1983;29:227-34.
  23. Kang SY, Yoon SY, Roh DH, Jeon MJ, Seo HS et al. 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.
  24. Kim HD, Cho HR, Moon SB, Shin HD, Yang KJ, Park BR et al. Effect of Exopolymers from Aureobasidum pullulans on formalin induced chronic paw inflammation in mice. J Microbiol Biotechnol. 2006;16:1954-60.
  25. Bamgbose SO, Noamesi BK. Studies on cryptolepine. II: Inhibition of carrageenan induced oedema by cryptolepine. Planta Med. 1981;41:392-6.
  26. Chen, Q. Method of Chinese Medicine Pharmacology. Beijing:Chinese People Health Press. 1996.
  27. Leach AA. Notes on a modification of the Neuman and Logan method for the determination of the hydroxyproline. Biochem J. 1960;74:70-1.
  28. Neuman RE, Logan MA. The determination of collagen and elastin in tissues. J Biol Chem. 1950;186:549-56.
  29. Neuman RE, Logan MA. The determination of hydroxyproline. J Biol Chem. 1950;184:299-306.
  30. Homer KA, Denbow L, Beighton D. Spectrophotometric method for the assay of glycosaminoglycans and glycosaminoglycan depolymerizing enzymes. Anal Biochem. 1993;214:435-41.
  31. James B, Wyngaarden C. Textbook of Medicine. Philadelphia:WA Saunders. 1992:1508-15.
  32. 楊維傑 編著. 黃帝內經素問譯解. 台北市:台聯國風出版社. 1984:95-6, 328-36.
  33. 張仲景. 金櫃要略方論. 湖北:東方書店. 1950:30-9.
  34. 巢元方. 諸病源候論. 北京:人民衛生出版社. 1982:5-8.
  35. 王燾. 外臺秘要方. 서울:大星文化社. 1983:424.
  36. 陳無擇. 三因方. 大連:國風出版社. 1977:2-3.
  37. 金定濟. 診療要覽. 서울:東洋醫學硏究所. 1974:459-60.
  38. 김동현, 김형민, 류종훈, 엄재영, 김상찬, 양재하 외 3 명. 한방약리학. 서울:신일상사. 2006:86-7, 110-11, 150-52, 430-37.
  39. 김인락, 김호철, 국윤범, 박성주, 박용기, 박지하 외 12 명. 本草學. 서울:圖書出版 永林社. 2007:311-12, 374-77, 448-51, 486-7, 548-9.
  40. Gupta AK, Chow M. Prednicarbate(Dermatop): profile of a corticosteroid. J Cutan Med Surg. 2004;8:244-7.
  41. Abdel Salam OM, Baiuomy AR, EI batran S, Arbid MS. Evaluation of the anti inflammatory, anti nociceptive and gastric effects of Ginkgo biloba in the rat. Pharmacol Res. 2004;49:133-42.
  42. Chi YM, Nakamura M, Zhao AY, Yoshizawa T, Yan WM, Hashimoto F et al, Anti inflammatory activity of 4, 4' dihydroxy alpha truxillic acid. Biol Pharm Bull. 2006;29:489-93.
  43. Mirshafiey A, Cuzzocrea S, Rehm B, Mazzon E, Saadat F, Sotoude M. Treatment of experimental arthritis with M2000, a novel designed non steroidal anti inflammatory drug. Scand J Immunol. 2005;61:435-41.
  44. Ganguly S, Mula S, Chattopadhyay S, Chatterjee M. An ethanol extract of Piper betle Linn: mediates its anti inflammatory activity via down regulation of nitric oxide. J Pharm Pharmacol. 2007;59:711-8.
  45. 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.
  46. 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.
  47. Kontny E, Rudnicka W, Kowalczewski J, Marcinkiewicz J, Maslinski W. Selective inhibition of cyclooxygenase 2 generated prostaglandin$E_2$, synthesis in rheumatoid arthritis synoviocytes by taurine chloramine. Arthritis Rheum. 2003;48:1551-5.
  48. Fogel Petrovic M, Long JA, Knight DA, Thompson PJ, Upham JW. Activated human dendritic cells express inducible cyclo oxygenase and synthesize prostaglandin$E_2$, but not prostaglandin$E_2$. Immunol Cell Biol. 2004; 82:47-54.
  49. 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.
  50. Haraoui B, Thonar EJ, Martel Pelletier J, Goulet JR, Raynauld JP, Ouellet M et al, Serum keratan sulfate levels in rheumatoid arthritis: inverse correlation with radiographic staging. J Rheumatol. 1994;21:813-7.
  51. Thonar EJ, Lenz ME, Klintworth GK, Caterson B, Pachman LM, Glickman P et al. Quantification of keratan sulfate in blood as a marker of cartilage catabolism. Arthritis Rheum. 1985;28:1367-76.
  52. 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.
  53. 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.