• Title/Summary/Keyword: MMP-7

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Effect of Hataedock Method with Coptidis Rhizoma and Glycyrrhiza Uralensis in Allergic Rhinitis-induced Obese Mice (비만 유발 생쥐에서 Th2분화조절을 통한 황련-감초 하태독법의 알레르기성 비염 발현 억제효과)

  • Ahn, Sang Hyun;Jung, A Ram;Kim, Ki Bong
    • The Journal of Pediatrics of Korean Medicine
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    • v.33 no.2
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    • pp.22-31
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    • 2019
  • Objective This study is to learn the effects of Hataedock method using Coptidis rhizoma and Glycyrrhiza uralensis mixed extract on inflammatory response in allergic rhinitis-induced obese NC/Nga mice. Materials and Methods The mice were fed with high fat-diet to be obese, and were divided into 3 groups as follows; allergic rhinitis-induced obese mice group with Hataedock method (CGT, n=10), no treatment group (Ctrl), allergic rhinitis elicited obese mice group (ARE). To induce allergic rhinitis, NC/Nga mice of 3 weeks age were sensitized on 7, 8 and 9 weeks by ovalbumin antigen in intraperitoneal space. After 7 days of final sensitization, allergic rhinitis was initially induced in mice through nasal cavities for 5 days. After 1-week, allergic rhinitis was induced again by the same method. Histological examination was used to identify distribution of IL-4, CD40, STAT6, $Fc{\varepsilon}RI$, substance P, MMP-9, NF-${\kappa}B$ p65, iNOS and COX-2. Results Hataedock method significantly reduced IL-4, STAT6 and CD40 response (p<0.05). In CGT, the inhibition of Th2 differentiation decreased inflammatory mediators such as $Fc{\varepsilon}RI$, substance P, MMP-9, NF-${\kappa}B$ p65, iNOS and COX-2 (all p<0.05). The immunological improvement led reduction of respiratory epithelial damage and mucin secretion in goblet cell. Conclusion The results of this study show that the Hataedock method suppresses the expression of allergic rhinitis by decreasing the inflammatory mediators through the regulation of Th2 differentiation even when the inflammation reaction is increased by obesity. Therefore, Hataedock may have potential preventive measure of allergic rhinitis accompanied by obese.

Silymarin Attenuates Invasion and Migration through the Regulation of Epithelial-mesenchymal Transition in Huh7 Cells (간암세포주에서 상피간엽전환억제를 통한 Silymarin의 침윤 및 전이 억제 효과)

  • Kim, Do-Hoon;Park, So-Jeong;Lee, Seung-Yeon;Yoon, Hyun-Seo;Park, Chung Mu
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.3
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    • pp.337-344
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    • 2018
  • Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

Effects of Dokhwalgisaengtang-gami Water Extract on Osteoclast Differentiation and Osteoblast Function in RANKL-induced RAW 264.7 Cell (독활기생탕가미방(獨活寄生湯加味方)이 파골세포 분화 억제와 조골세포 활성에 미치는 영향)

  • Je, Yun-Mo;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.2
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    • pp.1-16
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    • 2013
  • Objectives: This study was performed to evaluate the effect of Dokhwalgisaengtang-gami water extract(DGG) on osteoporosis. Methods: The osteoclastogenesis and gene expression were determined in RANKL-stimulated RAW 264.7 cell. And osteoblastogenesis was also determined in rat calvarial cell. Results: The results were summarized as followes. 1. DGG decreased the number of TRAP positive cell in RANKL-stimulated RAW 264.7 cell. 2. DGG inhibited TRAP activity in RANKL-stimulated RAW 264.7 cell. 3. DGG decreased the expression of NAFTc1, MITF in RANKL-stimulated RAW 264.7 cell. 4. DGG increased the expression of iNOS, COX-2, IL-6 in RANKL-stimulated RAW 264.7 cell. 5. DGG decreased the expression of cathepsin K, MMP-9, TRAP in RANKL-stimulated RAW 264.7 cell. 6. DGG increased cell proliferation of rat calvarial cell. 7. DGG increased ALP activity in rat calvarial cell 8. DGG increased bone matrix protein, collagen synthesis and nodule formation in rat calvarial cell. Conclusions: It is concluded that DGG might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression. And DGG might increase the bone formation resulted from increase of osteoblast function.

Protective Effect of Mulberry and Lithospermum erythrorhizon Extracts on Anti-aging against Photodamage (오디 및 자초추출물의 피부 광노화 보호효과)

  • Jeong, Yoo Seok;Jung, Hee Kyoung;Hong, Joo-Heon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.11
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    • pp.1744-1752
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    • 2013
  • We investigated the protective effect of UVB inducing photodamage from mulberry extract (ME) and Lithospermum erythrorhizon extract (LE). The contents of total anthocyanin and shikonin as a color compound of ME and LE were 4.92 mg/g and 9.58 mg/g, respectively. The electron donating ability and superoxide radical scavenging activity of ME were 84.32% and 76.34%, respectively. The oxygen radical absorbance capacity of the ME ($545.37{\mu}moles$ TE/g) was higher than LE ($427.18{\mu}moles$ TE/g). MMP-1 production in the HS68 cells were exposed to UVB suppressed by treatment with $200{\mu}g/mL$ of ME (68.6%) and LE (32.7%). ME and LE were applied to a skin aging mouse model, which was induced by the irradiation of UVB to the backs of hairless mice. The value of skin erythema index, wrinkle depth and thickness, epidermis thickness, and collagenous fiber damage in the experiment groups (MEL: ME 3%, MEM: ME 5%, MEH: ME 7%, LEL: LE 3%, LEM: LE 5%, LEH: LE 7%) were remarkably reduced than in the control group (only UVB exposure group), while water capacity increased. The level of total wrinkles depth in the skin was decreased to be 30% of the control group by MEH and LEM. These results suggest that ME and LE are useful cosmetic materials for skin protection against UVB-inducing.

Conditioned Medium of Soybean Extract Treated Osteoblasts Inhibits RANKL Induced Differentiation of Osteoclasts (대두추출물을 처리한 조골세포 조건배양액은 RANKL에 의해 유도된 파골세포 분화를 억제)

  • Park, Kyung-Ho;Ju, Won-Chul;Yeo, Joo-Hong;Lee, Kwang-Gill;Cho, Yun-Hi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.1
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    • pp.64-70
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    • 2010
  • Soybean is of particular interest as a food supplement of isoflavones for inhibiting bone resorption in postmenopausal woman. These beneficial effects of isoflavones are caused by functioning as partial agonists or antagonists of estrogen, of which anti-resorptive effect is mediated indirectly through paracrine factors produced by osteoblasts that act on osteoclasts. In this study, the indirect effect of soybean on osteoclastic differentiation of RAW264.7 cells were investigated. The conditioned medium was collected from MC3T3-E1 osbeoblasts treated with 0.001 mg/mL~0.1 mg/mL soybean extracts for 6 days, mixed in 1:1 ratio with osteoclast medium, and then added into RAW264.7 cells with receptor activator of nuclear factor kappa B ligand (RANKL), a differentiation inducer for 3 days. Of paracrine factors in the conditioned medium, the protein expression of osteoprotegerin (OPG) with soybean extract was specifically higher in a dose dependent manner than with $10^{-9}$ M~$10^{-6}$ M of estrogen, genistein or daidzein standards. In RAW264.7 cells, the conditioned medium with soybean inhibited RANKL induced osteoclastic differentiation as total number of multinucleated tartrateresistant alkaline phosphatase (TRAP)-positive osteoclasts and protein expression of MMP-9 were significantly decreased. Coupled with the low expression of estrogen receptor $\alpha$ and $\beta$ proteins in RANKL treated RAW264.7 cells, we demonstrate that the conditioned medium of soybean treated osteoblasts inhibits RANKL induced differentiation of osteoclasts with the selective expression of OPG in osteoblasts.

Effect of Kyejakjimo-tangkami (Guishaozhimu-tangjiawei) on Osteoarthritis (계작지모양가미방(桂芍知母湯加味方)이 골관절염에 미치는 영향)

  • Hong, Seong-Min;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.23 no.4
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    • pp.39-57
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    • 2013
  • Objectives The purpose of this study is to prove the effect of Kyejakjimotangkami(KMK) on osteoarthritis. Methods We checked antioxidant activity and measured production of $IL-1{\beta}$, IL-6, TNF-${\alpha}$ in RAW 264.7 cell after treat by KMK. Then we measured hind paw weight of Wister Rat with arthritis induced by MIA after KMK oral administration, checked Prostaglandin E2, IL-$1{\beta}$, IL-6, TNF-${\alpha}$, Osteocalcin, TIMP-1, MMP-9, LTB-4 in serum, ran histopathological test and ${\mu}CT$-arthrography. Results 1. DPPH radical Scavenging was increased depend on concentration of KMK ethanol extract in RAW 264.7 cell. 2. Production of NO was significantly decreased by KMK ethanol extract on concentration of $200{\mu}g/ml$ in RAW 264.7 cell. 3. Production of IL-$1{\beta}$ was significantly decreased by KMK ethanol extract on concentration of $200{\mu}g/ml$. And Production of IL-6, TNF-${\alpha}$ were significantly decreased KMK ethanol extract of every concentration in RAW 264.7 cell. 4. Result of checking hind paw weight when administered KMK ethanol extract to Wister Rat with arthritis induced by MIA was significantly higher than control group and similar to normal group. 5. Production of Prostaglandin E2, IL-$1{\beta}$, Osteocalcin, TIMP-1, MMP-9 and LTB-4 in serum was significantly decreased by KMK ethanol extract after administerd to Wister Rat with arthritis induced by MIA. 6. In Hematoxylin & Eosin staining and Safranin-O staining, we could find inflammation of synovial cell, infiltration of macrophage and granulocyte and degeneration of cartilage and bone were decreased in comparison with control group. 7. When checked cartilage volume to examine degree of cartilage degeneration using ${\mu}CT$-arthrography, volume of cartilage was increased in comparison with control group. Conclusions Comparison of the results for this study showed that KMK ethanol extract have anti-inflammatory effectiveness and can protect cartilage and bone. So we expect that KMK can be used as a effective drugs for osteoarthritis.

The Relation of Residual Pleural Thickening with Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases of Pleural Effusion in Patients with Tuberculous Pleuritis (결핵성 흉막염 환자에서 흉수 내 Matrix Metalloproteinases 및 Tissue Inhibitors of Metalloproteinases 농도와 잔여 흉막비후와의 관계)

  • Choi, Youngkwon;An, Chang Hyeok;Kim, Yu Jin;Kyung, Sun Young;Lee, Sang Pyo;Park, Jeong Woong;Jeong, Sung Hwan
    • Tuberculosis and Respiratory Diseases
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    • v.65 no.1
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    • pp.7-14
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    • 2008
  • Background: Residual pleural thickening (RPT) is the most frequent complication of tuberculous pleurisy (TP), and this can happen despite of administering adequate anti-tuberculous (TB) therapy. Yet there was no definite relation between RPT and other variables. The aim of this study was to examine matrix metalloproteinases (MMPs) and the inhibitors of metalloproteinases (TIMPs) and to identify the factors that can predict the occurrence of RPT. Methods: The patients with newly-detected pleural effusions were prospectively enrolled in this study from January 2004 to June 2005. The levels of MMP-1, -2, -8 and -9, and TIMP-1 and -2 were determined in the serum and pleural fluid by ELISA. The residual pleural thickness was measured at the completion of treatment and at the point of the final follow-up with the chest X-ray films. Results: The study included 39 patients with pleural fluid (PF). Twenty-three had tuberculous effusion, 7 had parapneumonic effusion, 7 had malignant effusion and 2 had transudates. For the 17 patients who completed the anti-TB treatment among the 23 patients with TP, 7 (41%) had RPT and 10 (59%) did not. The level of PF TIMP-1 in the patients with RPT ($41,405.9{\pm}9,737.3ng/mL$) was significantly higher than that of those patients without RPT ($29,134.9{\pm}8,801.8$) at the completion of treatment (p=0.032). In 13 patients who were followed-up until a mean of $8{\pm}5$ months after treatment, 2 (15%) had RPT and 11 (85%) did not. The level of PF TIMP-2 in the patients with RPT ($34.4{\pm}6.5ng/mL$) was lower than that of those patients without RPT ($44.4{\pm}15.5$) at the point of the final follow-up (p=0.038). Conclusion: The residual pleural thickening in TP might be related to the TIMP-1 and TIMP-2 levels in the pleural fluid.

Skin Anti-aging Effect of Forsythia viridissima L. Extract (연교추출물의 피부 항노화 효과)

  • Kim, Mi-Jin;Kim, Ja-Young;Jung, Teak-Kyu;Choi, Sang-Won;Yoon, Kyung-Sup
    • KSBB Journal
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    • v.21 no.6 s.101
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    • pp.444-450
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    • 2006
  • Skin anti-aging effect of Forsythia viridissima L. extract was evaluated by using antioxidant assay, expression of type I procollagen, and UVA-induced matrix metalloproteinase-1 in human dermal fibroblasts. Matairesinol-rich Forsythia viridissima L. extract was showed the scavenging activity of radicals and reactive oxygen species with the $IC_{50}$ values of $4.50\;{\mu}m/ml$ against 1,1-diphenyl-2-picrylhydrazly radical and $542.43\;{mu}m/ml$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. The type I procollagen was increased 33.76% by treatment with matairesinol-rich Forsythia viridissima L. extract, and UVA-induced MMP-1 was reduced 35.78% in a dose dependent manner. In the human skin irritation test, 2% matairesinol-rich Forsythia viridissima L. extract did not show any adverse effect. Also, the clinical study indicated that a cream group treated with 0.2% matairesinol-rich Forsythia viridissima L. extract significantly reduced skin wrinkles, as compared with a non-treated cream group (p < 0.05). These results suggest that Forsythia viridissima L. extract may be useful as a potential source of functional anti-aging cosmetics.

The Effect of Deer Antler Herbal Acupuncture Control to Hyper-inflammatory Responses on Synovial Membrane by LPS-induced Arthritis (약용약침(藥茸藥鍼)이 LPS 유발(誘發) 관절염(關節炎)의 윤활관절막내(潤滑關節膜內) 과다염증반응(過多炎症反應) 조절(調節)에 미치는 영향(影響))

  • Chung, Yong-Re;Lee, Seung-Deok;Byun, Hyuk;Park, In-Shik;Jung, Chan-Yung;Lee, Chang-Hwan;Kim, Kap-Sung
    • Journal of Acupuncture Research
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    • v.24 no.4
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    • pp.167-181
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    • 2007
  • Objectives: To evaluate expression of MIF mRNA, MIF, $TNF-{\alpha}$, $IL-6R-{\alpha}$, STAT-3, $NF-{\kappa}B$ p65, COX-2 and iNOS, MMP-9mRNA after injecting deer antler herbal acupuncture solution in a LPS rat model. Methods: The experiment was divided in category of the control group, RA group, and NA group. RA was induced in the mice via injecting 300ug/kg LPS. The deer antler herbal acupuncture solution 50ug/kg was applied on $ST_{35}$(犢鼻) and EX-LE201(內膝眼) for 19days from $3^{rd}$ day of RA inducement. Results: 1. In the deer antler herbal acupuncture solution treated RAW 264.7cell, the mRNA expression of cytokines, RA related inflammation factors, such as the MIF, COX- 2, iNOS, and MMP-g reduced concentration dependently. 2. In the deer antler herbal acupuncture treated mice's synovial membrane, decrease in the cell replication of synovial joint cells, regeneration of blood vessel, fibrosis and fibroblastic cells expansion were observed. 3. Positive reaction of RA-related cytokines MIF, $TNF-{\alpha}$, $IL-6R-{\alpha}$, STAT3, COX-2, iNOS, $NF-\;{\kappa}B$ p65, MMP-9 was reduced. Conclusion : On the basis of the results, it was concluded that deer antler herbal acupuncture extract has significant protecting ability against acute progressive RA by inhibiting the production of MIF, as a top in cytokines related to inflammation.

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Effects on Redox Status and NF-${\kappa}B$ Signaling by Ojunghwan (오정환(五精丸)이 ob/ob mouse에서 Redox Status 및 NF-${\kappa}B$ Signaling에 미치는 영향)

  • Baek, Ki-Beom;Jeong, Ji-Cheon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.5
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    • pp.1202-1209
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    • 2008
  • Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}\;{O_2}^-$) and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the effects of Ojunghwan on the generation of peroxynitrite ($ONOO^-$), nitric oxide (NO) and superoxide anion radical (${\cdot}\;{O_2}^-$), and on the expression of $NF-{\kappa}B$-dependent inflammatory proteins in ob/ob mice. Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received the standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blot was performed using anti-phospho $I{\kappa}B-{\alpha}$, $anti-IKK-{\alpha}$, $anti-NF-{\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 and anti-MMP-9 antibodies, respectively. Ojunghwan inhibited the generation of $ONOO^-$, NO and ${\cdot}\;{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}\;{O_2}^-$ and $PGE_2$ were inhibited in the Ojunghwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas that were improved in the Ojunghwan-administered groups. Ojunghwan inhibited the expression of $phospho-I{\kappa}B-{\alpha}$, $IKK-{\alpha}$, $NF-{\kappa}B$ (p50, p65), COX-2, iNOS, VCAM-1 and MMP-9 genes. These results suggest that Ojunghwan is an effective scavenger of $ONOO^-$, ${\cdot}\;{O_2}^-$, NO and $PGE_2$, and has an inhibitory effect on the expression of $NF-{\kappa}B$-dependent inflammatory genes in ob/ob mice. Therefore, Ojunghwan might be used as a potential therapeutic drug against the inflammation process and inflammation- related diseases.