Regulatory mechanism of Angelica Gigas extract powder on matrix metalloproteinases in vitro and in vivo model

참당귀 추출분말이 in vitro and in vivo model에서 MMPs 조절 기전

  • Kwon, Jin-Hwan (Natural Products Medical Research Institute, Nutragen Co.) ;
  • Han, Min-Seok (Natural Products Medical Research Institute, Nutragen Co.) ;
  • Lee, Yong-Moon (College of Pharmacy, Chungbuk National University)
  • 권진환 (뉴트라젠 천연물의학연구소) ;
  • 한민석 (뉴트라젠 천연물의학연구소) ;
  • 이용문 (충북대학교 약학대학 생물분석화학교실)
  • Received : 2015.10.21
  • Accepted : 2015.11.13
  • Published : 2015.12.25


The precise mechanism underlying the therapeutic efficacy of an extraction powder of Angelica gigas (AGE) for the treatment of degenerative osteoarthritis was investigated in primary cultured rabbit chondrocytes and in a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. The treatment with AGE (50 μg/mL) effectively inhibited NF-B activation. The anti-inflammatory mechanism was clarified by gelatin zymography and western blotting measurements of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activities. The AGE (50 μg/mL) treatment significantly reduced MMP-9 activity. The constituents of AGE— decursinol, decursin, and decursinol angelate—were determined by LC-MS/MS after a 24 hr treatment of rabbit chondrocytes. The contents of the major products, decursin and decursinol angelate, were 3.62±0.47 and 2.14 ±0.36 μg/mg protein, respectively in AGE-treated (50 μg/mL) rabbit chondrocytes. An in vivo animal study on rats fed a diet containing 25, 50, and 100 mg/kg AGE for 3 weeks revealed a significant inhibition of the MMPs in the MIA-induced rat articular cartilage. The genetic expression of arthritic factors in the articular cartilage was examined by RT-PCR of collagen Type I, collagen Type II, aggrecan, and MMP (MMP3, MMP-9, MMP13). Specifically, AGE up-regulated the expression of collagen Type I, collagen Type II, and aggrecan and inhibited MMP levels at all tested concentrations. Collectively, AGE showed a strong specific site of action on MMP regulation and protected against the degeneration of articular cartilage via cellular regulation of MMP expression both in vitro and in vivo.


Angelica gigas;osteoarthritis;MMPs;Decursin;Decursinol angelate;ectract


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