• 대한한의학회지
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• 제27권1호
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• pp.220-228
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• 2006

Objectives : Interleukin-1 (IL-1)${\beta}$ in articular chondrocytes regulates differentiation, apoptosis, and inflammatory responses. It is still controversial, So, we investigated IL- $1{\beta}$ induces chondrocytes dedifferentiation and death. Also, we studied the role of the mitogen-activated protein kinase (MAPK) subtypes on IL-$1{\beta}$-induced dedifferentiation and apoptosis. Methods : To evaluation of dedifferentiation by chemokines of chondrocytes, we assessed such as proteoglycan, collagen, MMP-3 and MMP-13 by RT-PCR analysis. Also, to assess of apoptosis effect by chemokines, we measured annexin V/propidium iodode (PI) and sub G1 cells in chondrocytes by flowcytometric analysis Results : IL-$1{\beta}$ treatment did not affect activation of ERK-1/2, but stimulation of p38 kinase. Inhibition of phospho ERK-1/2 with PD98059 enhanced IL-1b-induced dedifferentiation, and apoptosis up to 13.5%, whereas inhibition of phospho p38 kinase with SB203580 inhibited dedifferentiation, and apoptosis. Conclusions : Our results indicate that SB203580, p38 kinase inhibitor, inhibits IL-$1{\beta}$-induced dedifferentiation, and apoptosis by the inhibition of type II collagen expression and proteoglycan synthesis of rabbit articular chondrocytes.

• 동의생리병리학회지
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• 제20권2호
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• pp.436-441
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• 2006

Rheumatoid arthritis is a chronic, systemic, and inflammatory autoimmune disorder that affects 1% of the adult population worldwide. Osteoarthritis is a multifactorial disease with high morbidity that is characterized by degradation of the matrix and destruction of articular cartilage. In this study, we examined the inhibition effect of Trachelospermi Caulis on the inflammation($TNF-{\alpha}$, $IL-1{\beta}$, NO), cartilage protection(MMP-13), and cell death in arthritis. RAW 264.7 and SW 1353 cells were cultivated in DMAE(GibcoBRL, USA) with 5% FBS and Fungizone in $37^{\circ}C$, 5% CO2. THP-1 cells were cultivated in RPMI(GibcoBRL, USA) with 5% FBS and Fungizone in $37^{\circ}C$, 5% CO2. Activity of caspase-3, XIAP, Cytochrome C in the cell was examined by using western blot. The results obtained were as Follows; Concentration of nitric oxide in Trachelospermi Caulis treatment group significantly decreased compared with that of non-treatment group (P<0.05). In treated group, Concentration of Trachelospermi Caulis was not significantly associated with cell death. Concentration of $TNF-{\alpha}$ and $IL-1{\beta}$ in Trachelospermi Caulis treatment group decreased significantly compared with that of none treatment group (P<0.05). Relative density of MMP-13 in Trachelospermi Caulis treatment group decreased significantly compared with that of none treatment group and dose-response relationship was observed. After treatment of staurosporin in SW1353 which increases cell death, in Trachelospermi Caulis treated group, the cell death was effectively decreased. In conclusion, these results suggest that Trachelospermi Caulis inhibit inflammation and cell death in arthritis. More researches about effect of Trachelospermi Caulis are considered to need.

• Nutrition Research and Practice
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• 제12권1호
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• pp.29-40
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• 2018

BACKGROUND/OBJECTIVES: Ultraviolet radiation (UV) is a major cause of skin photoaging. Previous studies reported that ethanol extract (PET) of Prunus persica (L.) Batsch flowers (PPF, peach flowers) and its subfractions, particularly the ethylacetate (PEA) and n-butanol extracts (PBT), have potent antioxidant activity and attenuate the UV-induced matrix metalloproteinase (MMP) expression in human skin cells. In this study, we investigated the protective activity of PPF extract against UV-induced photoaging in a mouse model. MATERIALS/METHODS: Hairless mice were treated with PET or a mixture of PEA and PBT either topically or orally along with UV irradiation. Histological changes and biochemical alterations of mouse skin were examined. Major phenolic compounds in PPF extract were analyzed using an ACQUITY UPLC system. RESULTS: The overall effects of topical and oral treatments with PPF extract on the UV-induced skin responses exhibited similar patterns. In both experiments, the mixture of PEA and PBT significantly inhibited the UV-induced skin and epidermal thickening, while PET inhibited only the UV-induced epidermal thickening. Treatment of PET or the mixture of PEA and PBT significantly inhibited the UV-induced MMP-13 expression, but not type I collagen expression. Topical treatment of the mixture of PEA and PBT with UV irradiation significantly elevated catalase, superoxide dismutase (SOD) and glutathione-peroxidase (GPx) activities in the skin compared to those in the UV irradiated control group, while oral treatment of the mixture of PEA and PBT or PET elevated only catalase and SOD activities, but not GPx. Thirteen phytochemical compounds including 4-O-caffeoylquinic acid, cimicifugic acid E and B, quercetin-3-O-rhamnoside and kaempferol glycoside derivatives were identified in the PPF extract. CONCLUSIONS: These results demonstrate that treatment with PET or the mixture of PEA and PBT, both topically or orally, attenuates UV-induced photoaging via the cooperative interactions of phenolic components having anti-oxidative and collagen-protective activities.

• 생약학회지
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• 제39권1호
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• pp.1-6
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• 2008

AIF has been formulated using three herbs known to have anti-inflammatory and anti-osteolytic effects. In this study, the potential therapeutic effects of AIF for osteoarthritis were assessed in vitro and in vivo. The effects of AIF on the cartilage and bone protection (MMP-13 expression, GAG degradation, OPG release) were examined, in vitro. In addition, the therapeutic effect of AIF was evaluated using a chemical-induced osteoarthritis rat model. Rats were injected with iodoacetate intraarticularly in one knee joint and treated with the oral administration of 100 mg/kg AIF-glucosamine once a day for 3 weeks. And then, destruction of cartilage and bone was evaluated by histopathological assessment. AIF significantly inhibited the production of MMP13 and GAG in a dose dependent manner in vitro. Also, AIF increased the production of OPG. In OA rat model, the AIF-glucosamine treated group reduced cartilage destruction, compared to vehicle or glucosamine treated group. AIF showed potent protective effects for the destruction of cartilage and bone, in vitro and in vivo. These results suggest that AIF contains effective compound(s) which may modify the progression of arthritis.

• Journal of Periodontal and Implant Science
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• 제33권4호
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• pp.585-597
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• 2003

Porphyromonas gingivalis has been implicated as an important periodontophathic bacterium in the etiology and progression of periodontal diseases. It has been reported that P.gingivalis may mediate periodontal destruction not only directly through its virulence factors, but also indirectly by including complex host mediated inflammatory reponses. The purpose of this study was t o evaluate the effects of P.gingivalis on the bone formation and resorption by osteoblasts. For this purpose, after determining the concentration below which sonicated P.gingivalis extracts (SPEs) have no cytotoxicity on mouse calvarial primary osteoblastic (POB) cells, we investigated the effects of SPEs on the alkaline phosphatase (ALP) activity, matrix metalloproteinase (MMP) expression (MMP-2, -9, 13), and prostaglandin $E_2$ ($PGE_2$) release in POB cells by treatment with SPEs below that concentration. The results were as follows; 1. SPEs showed no cytotoxic effect on POB cells up to a concentration of 1 ${\mu}m$/ml. 2. The treatment with SPEs reduced ALP activity in a dose-dependent manner in POB cells, In addition, when we investigated the effect of SPEs (1 ${\mu}m$/ml) on ALP activity for different exposure periods, statistically significant inhibition of ALP activity was shown at 2 days of exposure, and further significant inhibition occurred by extending the periods of exposure. 3. The treatment with SPEs stimulated the gene expression of MMP-9 in POB cells. 4. The pre-treatment with SPEs increased the amount of $PGE_2$ released in POB cells. In summary, the present study shows that P.gingivalis could inhibit osteogenesis and stimulate bone resorption not only by reducing ALP activity but also by increasing MMP-9 mRNA expression in osteoblasts, possibly through an endogenous $PGE_2$ pathway. In addition, our results suggest that if P.gingivalis affects osteoblasts in early differentiation stage, such effects by P. gingivalis could be irreversible.

• Journal of Microbiology and Biotechnology
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• 제28권7호
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• pp.1199-1208
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• 2018

Osteoarthritis is a disease that affects the articular cartilage and osseous tissue, and can be worsened by aging, overweight status, and post-traumatic arthritis. The present study aimed to evaluate the effect of ID-CBT5101 (tyndallized Clostridium butyricum) on bone metabolism and the inflammatory response in a monosodium iodoacetate-induced rat model of osteoarthritis. ID-CBT5101 was administered orally at doses of $10^8$ or $10^{10}CFU/day$ for 2 weeks before direct injection of monosodium iodoacetate ($3mg/50{\mu}l$ of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral ID-CBT5101 for another 4 weeks. We evaluated the treatment effects based on serum biomarkers, mRNA expression, morphological and histopathological analyses of the knee joints, and weight-bearing distribution analysis. Compared with those in control rats, the ID-CBT5101 treatments significantly reduced the serum concentration of inflammation and bone metabolism markers (i.e., COX-2, IL-6, $LTB_4$, and COMP), and significantly increased the concentration of $IFN-{\gamma}$ and glycosaminoglycans. In addition, the ID-CBT5101 treatments inhibited the mRNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases (i.e., MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and TIMP-2). Furthermore, the ID-CBT5101 treatments effectively preserved the knee cartilage and synovial membrane, and significantly decreased the amount of fibrous tissue. Moreover, compared with that of the negative control group, the ID-CBT5101 treatments increased the weight-bearing distribution by ${\geq}20%$. The results indicate that ID-CBT5101 prevented and alleviated osteoarthritis symptoms. Thus, ID-CBT5101 may be a novel therapeutic option for the management of osteoarthritis.

• 한국식품영양과학회지
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• 제45권5호
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• pp.634-641
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• 2016

본 연구에서는 오디추출복합물(mulberry extract complex, MEC)의 퇴행성관절염 증상 완화 및 개선 효과 가능성을 탐색하기 위하여 monosodium iodoacetate(MIA)로 유도한 퇴행성관절염 in vivo 실험모델을 이용하였다. 연골의 주요 구성성분인 glycosaminoglycan(GAG) 및 collagen의 농도를 실험동물의 연골에서 측정한 결과 MIA로 인해 감소하였던 GAG 및 collagen의 농도가 MEC를 경구 투여한 실험군에서 농도 의존적으로 증가하였다. 또한 교원질 합성을 억제하고 분해를 촉진하는 matrix metalloproteinase-2, 9, 13의 농도를 측정한 결과는 MEC의 농도에 따라 감소하는 결과를 보여주었다. 연골 손상 지표인 cartilage oligomeric matrix protein과 C-terminal telopeptide 2의 측정결과에서는 대조군보다 유의성 있는 감소를 나타내어 MEC가 퇴행성관절염의 진행 억제에 도움을 줄 수 있을 것으로 생각된다. 관절염 지수 평가에서도 MEC는 모든 농도에서 대조군보다 유의성 있게 개선되는 결과를 나타내었다. 이상의 실험 결과를 통하여 MEC가 퇴행성관절염에서 나타나는 연골 구성성분의 분해를 억제하고, 여러 중요한 퇴행성관절염 진행 인자를 효과적으로 억제하여 결국 연골파괴 감소와 더불어 통증을 줄여줌으로써 퇴행성관절염에 대한 증상 완화 및 개선 효과가 있을 수 있는 건강기능식품의 원료로 활용될 수 있을 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2087-2093
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• 2012

Previous evidence showed ${\beta}1$, 3-N-acetylglucosaminyltransferase 8 (${\beta}3GnT8$), which can extend polylactosamine on N-glycans, to be highly expressed in some cancer cell lines and tissues, indicating roles in tumorigenesis. However, so far, the function of ${\beta}3GnT8$ in laryngeal carcinoma has not been characterized. To test any contribution, Hep-2 cells were stably transfected with sense or interference vectors to establish cell lines that overexpressed or were deficient in ${\beta}3GnT8$. Here we showed that cell proliferation was increased in ${\beta}3GnT8$ overexpressed cells but decreased in ${\beta}3GnT8$ knockdown cells using MTT. Furthermore, we demonstrated that change in ${\beta}3GnT8$ expression had significant effects on tumor growth in nude mice.We further provided data suggesting that overexpression of ${\beta}3GnT8$ enhanced the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the mRNA and protein levels, associated with shedding of tissue inhibitors of metalloproteinase TIMP-2. In addition, it caused increased production of transforming growth factor beta 1 (TGF-${\beta}1$), whereas ${\beta}3GnT8$ gene knockdown caused the reverse effect. The results may indicate a novel mechanism by which effects of ${\beta}3GnT8$ in regulating cellular proliferation are mediated, at least in partvia targeting MMPs/TIMPs and TGF-${\beta}1$ in laryngeal carcinoma Hep-2 cells. The finding may lay a foundation for further investigations into the ${\beta}3GnT8$ as a potential target for therapy of laryngeal carcinoma.

• 한국식품저장유통학회지
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• 제19권5호
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• pp.792-798
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• 2012

신선초 추출물의 접촉성 아토피 피부염 완화효과를 확인하고 이의 소재를 개발하기 위한 목적으로 신선초 DW 추출물, 50% 에탄올 추출물, 100% 에탄올 추출물을 DNFB로 아토피를 유도한 마우스 동물모델에 각각 처리하여 in vivo 실험과 in vitro 실험을 실시하였다. 그 결과, 신선초 추출물을 처리한 군의 귀 손상정도가 대조군에 비해 감소되었으며, 귀 조직을 HE 염색으로 전체 귀 두께와 상피 두께를 측정하였을 때에도 대조군에 비해 상당한 감소를 나타냈다. 또한 RT-PCR로 염증 분자마커인 MMP series의 mRNA 발현수준을 검토한 결과, 신선초 추출물은 MMPs에 비의존적으로 마우스 아토피 피부염의 완화작용에 작용하는 것으로 나타났다. 마지막으로 염증반응을 유도한 마우스 비장조직세포에서 염증성 cytokine인 IL-4는 신선초 녹즙에서 농도 의존적으로 감소되었으며, IL-13 또한 신선초 녹즙과 에탄올 추출물에서 상당한 억제효과가 있음을 확인하였다. 이상의 결과로 신선초 추출물의 항아토피 활성을 확인 하였으며, 관련 제품 개발에 유용한 소재가 될 가능성을 확인하였다.

• Journal of Chest Surgery
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• 제44권6호
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• pp.387-391
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• 2011

Background: The relationship between the degree of expression of matrix metalloproteinases or tissue inhibitor of metalloproteinases and venous reflux remains to be investigated. Materials and Methods: Primary varicose vein tissues were obtained from 23 patients, 18 females and 5 males, aged from 19 to 73. Cephalic or basilic veins were obtained for the control group from 10 patients who underwent vascular access for maintenance hemodialysis. Two operative techniques (high ligation with stripping or endovenous laser coagulation) were used. The expression of matrix metalloproteinase-2 and 13 and tissue inhibitor of metalloproteinase-4 in the varicose vein group and control group was assessed semi-quantitatively by immunohistochemical slides stained with primary antibodies. Results: Twenty (87%) of the varicose vein group patients had greater or lesser saphenous vein diseases with reflux. The focal weak (+) stain for matrix metalloproteinases-2, and 13, and tissue inhibitor of matrix metalloproteinase-4 was dominant in the varicose vein group; the focal or diffuse strong stain (++ or +++) was prevalent in the control group. The differences were statistically significant (p<0.01). The degree of reflux and the duration of symptoms were not significantly related to the expression of MMP-13 (p=0.317 and p=0.654, respectively). Conclusion: Further study should be performed to investigate the relationship between the clinical characteristics related to venous hypertension or reflux and expression of MMPs and TIMP in varicose veins.