Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Protective Effects of a Mixed Medicinal Herb Extract (NUC1) on Collagenase-Induced Osteoarthritis in Rabbits

  • Sung-Gyu Lee (Department of Medical Laboratory Science, College of Health Science, Dankook University) ;
  • Hyun Kang (Department of Medical Laboratory Science, College of Health Science, Dankook University)
  • Received : 2023.03.29
  • Accepted : 2023.07.12
  • Published : 2023.11.28
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Abstract

NUC1 (Nutraceutical compound 1) is an ethanol extract composed of a formulation based on medicinal herbs traditionally used for the treatment of arthritis in Korea and China. This study investigated the therapeutic effects of NUC1 on osteoarthritis (OA). The protective effect of NUC1 on OA was tested in a rabbit model of collagenase-induced arthritis (CIA) for 4 weeks. Results were compared among four groups (n = 9 per group): the normal group (untreated), the CIA group (vehicle control), the NUC1 group (CIA rabbits treated with 200 mg/kg NUC1), and the JOINS group (positive control, CIA rabbits treated with 200 mg/kg JOINS tablet). NUC1 significantly inhibited NO production (p < 0.05 at 125 ㎍/ml, p < 0.01 at 250 ㎍/ml, and p < 0.001 at 500 ㎍/ml) and iNOS expression in macrophages, in a concentration-dependent manner. NUC1 also inhibited the release and protein expression of MMP-1, 3, and 13, in TNF-α-induced chondrosarcoma cells in a concentration-dependent manner. In vivo, the MMP-1 and MMP-3 levels in synovial fluids were significantly (p < 0.05) lower in NUC1 group (77.50 ± 20.56 and 22.50 ± 7.39 pg/ml, respectively) than in the CIA group (148.33 ± 68.58 and 77.50 ± 20.46 pg/ml, respectively). Also, in histopathological, NUC1 ameliorated articular cartilage damage in OA by increasing the abundance of chondrocytes and proteoglycan in the articular cartilage. Thus, NUC1 showed promise as a potential therapeutic agent, and it can be generalized to a broader study population in different OA animal models.

Keywords

Acknowledgement

The present study was supported by the research fund of Dankook University in 2022.

References

  1. Orhan C, Juturu V, Sahin E, Tuzcu M, Ozercan IH, Durmus AS, et al. 2021. Undenatured type II collagen ameliorates inflammatory responses and articular cartilage damage in the rat model of osteoarthritis. Front. Vet. Sci. 8: 617789.
  2. Sifre V, Soler C, Segarra S, Redondo JI, Domenech L, Ten-Esteve A, et al. 2022. Improved joint health following oral administration of glycosaminoglycans with native type ii collagen in a rabbit model of osteoarthritis. Animals (Basel). 12. doi: 10.3390/ani12111401.
  3. Goldring MB, Goldring SR. 2010. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann. NY Acda. Sci. 1192: 230-237. https://doi.org/10.1111/j.1749-6632.2009.05240.x
  4. Kraus VB. 1997. Pathogenesis and treatment of osteoarthritis. Med. Clin. North Am. 81: 85-112. https://doi.org/10.1016/S0025-7125(05)70506-X
  5. Dean DD, Martel-Pelletier J, Pelletier JP, Howell DS, Woessner JFJ.1989. Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritis cartilage. J. Clin. Investig. 84: 678-685. https://doi.org/10.1172/JCI114215
  6. Bijlsma JW, Berenbaum F, Lafeber FP. 2011. Osteoarthritis: an update with relevance for clinical practice. Lancet 377: 2115-2126. https://doi.org/10.1016/S0140-6736(11)60243-2
  7. Hawkey C, Laine L, Simon T, Beaulieu A, Maldonado-Cocco J, Acevedo E, et al. 2000. The rofecoxib osteoarthritis endoscopy multinational study group. Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo controlled trial. Arthritis Rheum. 43: 370-377. https://doi.org/10.1002/1529-0131(200002)43:2<370::AID-ANR17>3.0.CO;2-D
  8. Sim WH and Seo BI. 2018. A study on the effect comparative of Acanthopanax stem bark (ASB) and Acanthopanax root bark (ARB) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Kor. J. Herbol. 33: 53-66.
  9. Lee BK, Lee YC, Lee JC. 2010. Inhibitory effect of a decoction of Eucommiae ulmides Oliver and Dipsacus asperoides CY Cheng et TMAi on collagen II-induced arthritis mice. Kor. J. Herbol. 25: 55-63.
  10. Lee JS, Kim IS, Kim JH, Kim JS, Kim DH, Yun CY. 2008. Suppressive effects of Houttuynia cordata Thunb (Saururaceae) extract on Th2 immune response. J. Ethnopharmacol. 117: 34-40. https://doi.org/10.1016/j.jep.2008.01.013
  11. Jo HK, Kim DS, Kim JY, Park YM, Shin DY, Lee HY, et al. 2020. Anti-inflammatory effect of herbal complex HP-04 on degenerative osteoarthritis. Kor. J. Pharmacogn. 51: 122-130.
  12. Lee SG, Jeong HJ, Lee EJ, Kim JB, Choi SW. 2011. Antioxidant and anti-inflammatory activities of ethanol extracts from medicinal herb mixtures. Korea J. Food Sci. Technol. 43: 200-205. https://doi.org/10.9721/KJFST.2011.43.2.200
  13. Lee S. (1590 A.D.). 1978. Bon Cho Gang Mok [Compendium of material medica]. ChungKuK ChungEuiHak. Peking.
  14. Lee SG, Lee EJ, Park WD, Kim JB, Kim EO, Choi SW. 2012. Anti-inflammatory and anti-osteoarthritis effects of fermented Achyranthes japonica Nakai. J. Ethnopharmacol. 142: 634-641. https://doi.org/10.1016/j.jep.2012.05.020
  15. Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65: 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  16. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. 1982. Analysis of nitrate, nitrite and (15N) nitrate in biological fluids. Anal. Biochem. 126: 131-138. https://doi.org/10.1016/0003-2697(82)90118-X
  17. Gogly B, Groult N, Hornebeck W, Godeau G, Pellat B. 1998. Collagen zymography as a sensitive and specific technique for the determination of subpicogram levels of interstitial collagenase. Anal. Biochem. 255: 211-216. https://doi.org/10.1006/abio.1997.2318
  18. Kikuchi T, Sakuta T, Uamaguchi T. 1998. Intra-articular injection of collagenase experimental osteoarthritis in mature rabbits. Osteoarthr. Cartil. 6: 177-186. https://doi.org/10.1053/joca.1998.0110
  19. Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, et al. 2006. Osteoarthritis cartilage histopathology: grading and staging Osteoarthr. Cartil. 14: 13-29. https://doi.org/10.1016/j.joca.2005.07.014
  20. El-Baz FK, Salama AAA, Hussein RA. 2020. Dunaliella salina microalgae oppose thioacetamide-induced hepatic fibrosis in rats. Toxicol. Rep. 7: 36-45. https://doi.org/10.1016/j.toxrep.2019.10.017
  21. Troeberg L, Nagase H. 2011. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim. Biophys. Acta 1824: 133-145. https://doi.org/10.1016/j.bbapap.2011.06.020
  22. Felson DT. 2009. Developments in the clinical understanding of osteoarthritis. Arthritis Res. Ther. 11: 203.
  23. Martel-Pelletier J. 1998. Pathophysiology of osteoarthritis. Osteoarthr. Cartil. 6: 374-376. https://doi.org/10.1053/joca.1998.0140
  24. Benito MJ, Veale DJ, FitzGerald O, van den Berg W, Bresnihan B. 2005. Synovial tissue inflammation in early and late osteoarthritis. Ann. Rheum. Dis. 64: 1263-1267. https://doi.org/10.1136/ard.2004.025270
  25. Deng JS, Chiu CS, Huang SS, Shie PH, Lin TH, Huang GJ. 2011. Antioxidant, analgesic, and anti-inflammatory activities of the ethanol extracts of Taxillus liquidambaricola. J. Ethnopharmacol. 137: 1161-1171. https://doi.org/10.1016/j.jep.2011.07.041
  26. Tchetcerikov I, Lohmander LS, Verzijl N, Huizinga TW, Tekoppele JM, Hanemaaijer R, et al. 2005. MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann. Rheum. Dis. 64: 694-698. https://doi.org/10.1136/ard.2004.022434
  27. Brennan FM, McInnes IB. 2008. Evidence that cytokines play a role in rheumatoid arthritis. J. Clin. Investig. 118: 3537-3545. https://doi.org/10.1172/JCI36389
  28. Jeffery J. 1998. Interstitial collagenases. In Matrix Metalloproteinases: Parks WC, Mecham RP (eds.), pp. 15-38. Academic Press, San Diego, CA, USA.
  29. Visse R, Nagase H. 2003. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ. Res. 92: 827-839. https://doi.org/10.1161/01.RES.0000070112.80711.3D
  30. Birkedal-Hansen H. Moore WG, Bodden MK. 1993. Matrix metalloproteinases: a review. Crit. Rev. Oral Biol. Med. 4: 197-250. https://doi.org/10.1177/10454411930040020401
  31. Goldring MB. 2000. The role of the chondrocyte in osteoarthritis. Arthritis Rheum. 43: 1916-1926. https://doi.org/10.1002/1529-0131(200009)43:9<1916::AID-ANR2>3.0.CO;2-I
  32. Billinghurst RC, Dahlberg L, Ionescu M. 1997. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J. Clin. Investig. 99: 1534-1545. https://doi.org/10.1172/JCI119316
  33. Neuhold LA, Killar L, Zhao W, Sung ML, Warner L, Kulik J, et al. 2001. Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. J. Clin. Investig. 107: 35-44. https://doi.org/10.1172/JCI10564
  34. van den Berg WB. 2000. Pathophysiology of osteoarthritis. Joint Bone Spine 67: 555-556. https://doi.org/10.1016/S1297-319X(00)00216-5
  35. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. 2012. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 64: 1697-1707. https://doi.org/10.1002/art.34453
  36. Cunnane G, Fitzgerald O, Beeton C. 2001. Early joint erosions and serum levels of matrix metalloproteinase 1, matrix metalloproteinase 3, and tissue inhibitor of metalloproteinase 1 in rheumatoid arthritis. Arthritis Rheum. 44: 2263-2274. https://doi.org/10.1002/1529-0131(200110)44:10<2263::AID-ART389>3.0.CO;2-1
  37. Gosset M, Pigenet A, Salvat C, Berenbaum F, Jacques CJ. 2010. Inhibition of matrix metalloproteinase-3 and -13 synthesis induced by IL-1beta in chondrocytes from mice lacking microsomal prostaglandin E synthase-1. J. Immunol. 185: 6244-6252. https://doi.org/10.4049/jimmunol.0903315
  38. Li Y, Yang B, Baia JY, Xiaa S, Maoa M, Lia M, et al. 2019. The roles of synovial hyperplasia, angiogenesis and osteoclastogenesis in the protective effect of apigenin on collagen-induced arthritis. Int. Immunopharmacol. 73: 362-369. https://doi.org/10.1016/j.intimp.2019.05.024
  39. Hussain T, Tan B, Liu G, Oladele OA, Rahu N, Tossou MC. 2016. Health-promoting properties of Eucommia ulmoides: a review. Evid. Based Complement. Alternat. Med. 2016: 5202908.
  40. Choi JW, Huh K, Kim SH, Lee KT, Park HJ, Han YN. 2002. Antinociceptive and anti-rheumatoidal effects of Kalopanax pictus extract and its saponin components in experimental animals. J. Ethnopharmacol. 79: 199-204. https://doi.org/10.1016/S0378-8741(01)00383-X
  41. Fikry EM, Gad AM, Eid AH, Arab HH. 2019. Caffeic acid and ellagic acid ameliorate adjuvant-induced arthritis in rats via targeting inflammatory signals, chitinase-3-like protein-1 and angiogenesis. Biomed. Pharmacother. 110: 878-886. https://doi.org/10.1016/j.biopha.2018.12.041
  42. Du K, Fang X, Li Z. 2021. Ferulic acid suppresses interleukin-1β-induced degeneration of chondrocytes isolated from patients with osteoarthritis through the SIRT1/AMPK/PGC-1α signaling pathway. Immun. Inflamm. Dis. 9: 710-720. https://doi.org/10.1002/iid3.424
  43. Wang H, Yan Y, Pathak JL, Hong W, Zeng J, Qian D, et al. 2023. Quercetin prevents osteoarthritis progression possibly via regulation of local and systemic inflammatory cascades. J. Cell. Mol. Med. 27: 471-592.