Korean Journal of Medicinal Crop Science (한국약용작물학회지)

The Korean Society of Medicinal Crop Science (한국약용작물학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Supercritical Fluid Extract, Shikonin and Acetylshikonin from Lithospermum erythrorhizon on Chondrocytes and MIA-Induced Osteoarthritis in Rats

지치의 초임계추출물, Shikonin 및 Acetylshikonin의 연골세포 및 MIA 유도 관절염 모델에서의 효과

  • Kim, Geum Soog (Department of Herbal Crop Research, NIHHS, RDA) ;
  • Kim, Hwa Jin (YD Life Science Research Institute, YD Life Science Co. Ltd.) ;
  • Lee, Dae Young (Department of Herbal Crop Research, NIHHS, RDA) ;
  • Choi, Seung Min (YD Life Science Research Institute, YD Life Science Co. Ltd.) ;
  • Lee, Seung Eun (Department of Herbal Crop Research, NIHHS, RDA) ;
  • Noh, Hyung Jun (Department of Herbal Crop Research, NIHHS, RDA) ;
  • Choi, Jong Gil (YD Life Science Research Institute, YD Life Science Co. Ltd.) ;
  • Choi, Soo Im (YD Life Science Research Institute, YD Life Science Co. Ltd.)
  • 김금숙 (농촌진흥청 국립원예특작과학원 인삼특작부) ;
  • 김화진 ((주)와이디생명과학연구소) ;
  • 이대영 (농촌진흥청 국립원예특작과학원 인삼특작부) ;
  • 최승민 ((주)와이디생명과학연구소) ;
  • 이승은 (농촌진흥청 국립원예특작과학원 인삼특작부) ;
  • 노형준 (농촌진흥청 국립원예특작과학원 인삼특작부) ;
  • 최종길 ((주)와이디생명과학연구소) ;
  • 최수임 ((주)와이디생명과학연구소)
  • Received : 2013.10.10
  • Accepted : 2013.11.26
  • Published : 2013.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

This study investigates the effect of supercritical fluid extract (CMPB803-C) of Lithospermum erythrorhizon, shikonin and acetylshikonin isolated from Lithospermum erythrorhizon on IL-$1{\beta}$-induced chondrocytes and monosodium iodoacetate (MIA)-induced osteoarthritis in rat. Shikonin ($50{\mu}m$) and acetylshikonin ($3{\mu}M$) treatment reduced significantly the mRNA expression and enzyme activity of matrix metalloproteinase (MMP)-1, -3 and -13 in IL-$1{\beta}$-induced SW1353 chondrosarcoma cells. The chondro-protective effects of CMPB803-C and acetylshikonin were than analyzed in a rat OA model using a single intra-articular injection of MIA (1mg) in the right knee joint. CMPB803-C (200mg/kg) or acetylshikonin (5mg/kg) was orally administered daily for two weeks starting after 1 week of MIA injection. In the histological observation, CMPB803-C and acetylshikonin clearly improved OA lesions being comparable to or better that control group. Our results demonstrated that CMPB803-C and acetylshikonin as active compound of Lithospermum erythrorhizon have a strong chondro-protective effect in OA rats, which likely attributes to its anti-inflammatory activity and inhibition of MMPs production.

Keywords

References

  1. Ahn YH, Jin YH, Choe CY, Lee MK and Lee S. (2009). Ecological characteristics of Lithospermum erythrorhizon population in habitats. Korean Journal of Pharmacognosy. 40:289-297.
  2. Alaaeddine N, Okais J, Ballane L and Baddoura RM. (2012). Use of complementary and alternative therapy among patients with rheumatoid arthritis and osteoarthritis. Journal of Clinical Nursing. 21:198-204. https://doi.org/10.1111/j.1365-2702.2011.03826.x
  3. Altman RD. (2008). The future of herbal medicine in the treatment of osteoarthritis. Osteoarthritis and Cartilage. 16:S10-S11.
  4. Andujar I, Recio MC, Giner RM and Ríos JL. (2013). Traditional chinese medicine remedy to jury: The pharmacological basis for the use of shikonin as an anticancer therapy. Current Medicinal Chemistry. 20:2892-2898. https://doi.org/10.2174/09298673113209990008
  5. Bar-Yehuda S, Rath-Wolfson L, Del Valle L, Ochaion A, Cohen S, Patoka R, Zozulya G, Barer F, Atar E, Pina-Oviedo S. Perez-Liz G. Castel D and Fishman P. (2009). Induction of an anti-inflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 Treatment. Arthritis & Rheumatism. 60:3061-3071. https://doi.org/10.1002/art.24817
  6. Berenbaum F. (2013). Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis). Osteoarthritis and Cartilage. 21:16-21. https://doi.org/10.1016/j.joca.2012.11.012
  7. Billinghurst RC, Wu W, Ionescu M, Reiner A, Dahlberg L, Chen J, van Wart H and Poole AR. (2000). Comparison of the degradation of type II collagen and proteoglycan in nasal and articular cartilages induced by interleukin-1 and the selective inhibition of type II collagen cleavage by collagenase. Arthritis & Rheumatism. 43:664-672. https://doi.org/10.1002/1529-0131(200003)43:3<664::AID-ANR24>3.0.CO;2-D
  8. Bove SE, Calcaterra S, Huber C, Guzman RE, Schrier DJ and Kilgore KS. (2003). Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compound in a model of monosodium iodoacetate induced osteoarthritis. Osteoarthritis and Cartilage. 11:821–830. https://doi.org/10.1016/S1063-4584(03)00163-8
  9. Burrage PS, Mix KS and Brinckerhoff CE. (2006). Matrix metalloproteinases: Role in arthritis. Frontiers in Bioscience. 11:529-543. https://doi.org/10.2741/1817
  10. Chang YS, Kuo SC, Weng SH, Jan SC, Ko FN and Teng CM. (1993). Inhibition of platelet aggregation by shikonin derivatives isolated from Arnebia euchromoma. Planta Medica. 59:401-404. https://doi.org/10.1055/s-2006-959718
  11. Cheng HW, Chen FA, Hsu HC and Chen CY. (1995). Photochemical decomposition of alkannin/shikonin enantiomers. International Journal of Pharmaceutics. 120:137-144. https://doi.org/10.1016/0378-5173(94)00367-E
  12. Cheng YW, Chang CY, Lin KL, Huc CM, Lin CH and Kang JJ. (2008). Shikonin derivatives inhibited LPS-induced NOS in RAW264.7 cells via down-regulation of MAPK/NF-kB signaling. Journal of Ethnopharmacology. 120:264-271. https://doi.org/10.1016/j.jep.2008.09.002
  13. Chung HS, Kang M, Cho C, Park S, Kim H, Yoon YS, Kang J, Shin MK, Hong MC and Bae H. (2005). Inhibition of lipopolysaccharide and interferon-gamma-induced expression of inducible nitric oxide synthase and tumor necrosis factor-alpha by Lithospermi radix in mouse peritoneal macrophages. Journal of Ethnopharmacology. 102:412-417. https://doi.org/10.1016/j.jep.2005.06.028
  14. Combe R, Bramwell S and Field MJ. (2004). The monosodium iodoacetate model of osteoarthritis. Neuroscience Letter. 370:236-240. https://doi.org/10.1016/j.neulet.2004.08.023
  15. Guzman RE, Evans MG, Bove S, Morenko B and Kilgore K. (2003). Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial Joints: An animal model of osteoarthritis. Toxicologic Pathology. 31:619-624. https://doi.org/10.1080/01926230390241800
  16. Han J, Weng X and Bi K. (2008). Antioxidants from a Chinese medicinal herb-Lithospermum erythrorhizon. Food Chemistry. 106:2-10. https://doi.org/10.1016/j.foodchem.2007.01.031
  17. Huh JE, Park YC, Seo BK, Lee JD, Baek YH, Choi DY and Park DS. (2012). Cartilage protective and chondrogenic capacity of WIN-34B, a new herbal agent, in the collagenaseinduced osteoarthritis rabbit model and in progenitor cells from subchondral bone. Evidence-Based Complementary and Alternative Medicine. 2013:1-12.
  18. Hwang SY, Hwang BY, Kang SS, Kim CM, Park JH, Bae KH, Son KH, Lee SH, Chang SY, Kang SJ, Ro JS and Lee KS. (2000). Isolation and quantitative analysis of acetylshikonin from Lithospermi Radix. Korean Journal of Pharmacognosy. 31:295-299.
  19. Jhun HJ, Ahn K and Lee SC. (2010). Estimation of the prevalence of osteoarthritis in Korean adults based on the data from the fourth Korea national health and nutrition examination survey. Anesthesia and Pain Medicine. 5:201-206.
  20. Kim GS, Jeong TS, Kwon BM, Kim YO, Cha SW, Song KS and Baek NI. (2009). Inhibitory effect of acetylshikonin from Lithospermum erythrorhizon on LDL oxidation and FPTase activity. Journal of Applied Biological Chemistry. 52:221-225. https://doi.org/10.3839/jabc.2009.038
  21. Kim GS, Park CG, Lee KH, Choi J, Lee SE, Noh HJ, Lee JH and Kim SY. (2011). Investigation of shikonin pigments and antioxidant activity of the roots from Lithospermum erythrorhizon according to the different growth stages and areas of cultivation. Korean Journal of Medicinal Crop Science. 19:435-440. https://doi.org/10.7783/KJMCS.2011.19.6.435
  22. Kim JY and Kim SH. (2008). Shikonin, acetylshikonin, and isobutyroylshikonin inhibit VEGF-induced angiogenesis and suppress tumor growth in lewis lung carcinoma-bearing mice. Yakugaku Zasshi. 128:1681-1688. https://doi.org/10.1248/yakushi.128.1681
  23. Kim YO, Hong SJ and Yim SV. (2010). The efficacy of shikonin on cartilage protection in a mouse model of rheumatoid arthritis. Korean Journal of Physiology & Pharmacology. 14:199-204. https://doi.org/10.4196/kjpp.2010.14.4.199
  24. Li D, Yuan T, Zhang X, Xiao Y, Wang R, Fan Y and Zhang X. (2012) Icariin: A potential promoting compound for cartilage tissue engineering. Osteoarthritis and Cartilage. 20:1647-56. https://doi.org/10.1016/j.joca.2012.08.009
  25. Lee HH, Yoon JS and Song SY. (2010). Protective effect of Lithospermum erythrorhizon on galactosamine induced liver injury. Korean Journal of Microscopy. 40:29-35.
  26. Pan YM, Liang Y, Wang HS and Liang M. (2004). Antioxidant activities of several Chinese medicine herbs. Food Chemistry. 88:347-350. https://doi.org/10.1016/j.foodchem.2004.02.002
  27. Piecha D, Weik J, Kheil H, Becher G, Timmermann A, Jaworski A, Burger M and Hofmann MW. (2010). Novel selective MMP-13 inhibitors reduce collagen degradation in bovine articular and human osteoarthritis cartilage explants. Inflammation Research. 59:379-389. https://doi.org/10.1007/s00011-009-0112-9
  28. Rajasekar S, Park da J, Park C, Park S, Park YH, Kim ST, Choi YH and Choi YW. (2012). In vitro and in vivo anticancer effects of Lithospermum erythrorhizon extract on B16F10 murine melanoma. Journal of Ethnopharmacology. 21:335-345.
  29. Shingleton WD, Ellis AJ, Rowan AD and Cawston TE. (2000). Retinoic acid combines with interleukin-1 to promote the degradation of collagen from bovine nasal cartilage: Matrix metalloproteinase-1 and 13 are involved in cartilage breakdown. Journal of Cellular Biochemistry. 79:519-531. https://doi.org/10.1002/1097-4644(20001215)79:4<519::AID-JCB10>3.0.CO;2-U
  30. Staniforth V, Wang SY, Shyur LF and Yang NS. (2004). Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human TNF-${\alpha}$ promoter in vivo. The Journal of Biological Chemistry. 279:5877-5885. https://doi.org/10.1074/jbc.M309185200
  31. Tian L, Wang Z, Wu H, Wang S, Wang Y, Wang Y, Xu J, Wang L, Qi F, Fang M, Yu D and Fang X. (2011). Evaluation of the anti-neuraminidase activity of the traditional Chinese medicines and determination of the anti-influenza a virus effects of the neuraminidase inhibitory TCMs in vitro and in vivo. Journal of Ethnopharmacology. 137:534-542. https://doi.org/10.1016/j.jep.2011.06.002
  32. Wang JP, Raung SL, Chang LC and Kuo SC. (1995). Inhibition of hind-paw edema and cutaneous vascular plasma extravasation in mice by acetylshikonin. European Journal of Pharmacology. 272:87-95. https://doi.org/10.1016/0014-2999(94)00627-J
  33. Weng XC, Xiang GQ, Jiang AL, Liu YP, Wu LL, Dong XW and Duan S. (2000). Antioxidant properties of components extracted from pucoon(Lithospermum erythrorhizon Sieb. et Zucc.). Food Chemistry. 69:143-146. https://doi.org/10.1016/S0308-8146(99)00236-8

Cited by

  1. Potential of Pseudoshikonin I Isolated from Lithospermi Radix as Inhibitors of MMPs in IL-1β-Induced SW1353 Cells vol.17, pp.8, 2016, https://doi.org/10.3390/ijms17081350