• Title/Summary/Keyword: Matrix metalloproteinases

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Effect of Inonotus obliquus Extract on the Expression MMPs and HAS-2 (차가버섯 추출물의 MMPs 발현 저해 및 HAS-2 발현 증가효과)

  • Lee, So-Hun;Park, Sun-Hee;Lee, Kang-Hyuk;Park, Soo-Jin;Kim, Young-Heui
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.37 no.3
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    • pp.237-245
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    • 2011
  • In order to investigate the possibility of Inonotus obliquus extract as an active ingredient for wrinkle-care cosmetics, we prepared 70 % ethanolic extract of Inonotus obliquus and measured its DPPH radical scavenging activity and elastase inhibitory activity. We also evaluated the effect of Inonotus obliquus extract on expression of MMPs and HAS-2 in fibroblast and HaCaT cell, respectively. Inonotus Obliquus extract showed DPPH radical scavenging activity and elastase inhibitory activity in a dose-dependant manner ($SC_{50}$ = 91 ${\mu}g$/mL, $IC_{50}$=124 ${\mu}g$/mL). Inonotus obliquus extract inhibited the expression of MMP-1 mRNA 50 ~ 79 % at concentrations of 5 ~ 25 ${\mu}g$/mL, and reduced the expression of MMP-2 around 20 % at a concentration of 10 ${\mu}g$/mL. And it also reduced the expression of MMP-9 54 ~ 70 % in tconcentrations of 5 to 25 ${\mu}g$/mL. Furthermore, Inonotus obliquus extract increased HAS-2 mRNA expression in a dose-dependent manner in concentrations of 5 to 25 ${\mu}g$/mL without cytotoxicity. These results suggested that Inonotus Obliquus extract could be useful as an active ingredient for wrinkle-care cosmetics.

Inhibition of Hydrogen Sulfide-induced Angiogenesis and Inflammation in Vascular Endothelial Cells: Potential Mechanisms of Gastric Cancer Prevention by Korean Red Ginseng

  • Choi, Ki-Seok;Song, Heup;Kim, Eun-Hee;Choi, Jae-Hyung;Hong, Hua;Han, Young-Min;Hahm, Ki-Baik
    • Journal of Ginseng Research
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    • v.36 no.2
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    • pp.135-145
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    • 2012
  • Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide ($H_2S$) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating $H_2S$ generation. Because the incubation of endothelial cells with $H_2S$ has been known to enhance their angiogenic activities, we hypothesized that the amelioration of $H_2S$-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the $H_2S$ generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine ${\beta}$-synthase and cystathionine ${\gamma}$-lyase, enzymes that are essential for $H_2S$ synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this $H_2S$-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate $H_2S$-induced angiogenesis, implying that antagonistic action against $H_2S$-induced angiogenesis may be the mechanism underlying the gastric cancer preventive effects of KRGE in H. pylori infection.

Target Proteins Involved in Aging Mechanism as an Aging Molecular Marker (노화 분자마커로서 노화기전에 관여하는 타켓 단백질)

  • Kim, Moon-Moo
    • Journal of Life Science
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    • v.26 no.8
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    • pp.983-989
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    • 2016
  • All cells composing of our body undergo their destiny such as proliferation, differentiation, necrosis, apoptosis and senescence depending on their circumstance with time. The errors occurring in these processes develop several aberrations in phenotypes including cancer, inflammation, aging and diseases. New strategy and approach are required to screen anti-aging compounds derived from natural products. Therefore, here we explain the target proteins to play a key role in aging mechanism. In the first place, matrix metalloproteinases (MMPs) are involved in metastasis, chronic inflammation and skin aging as an aging marker. In particular, histone deacetylases (HDACs) give a great attention to aging researchers who try to extend the life span of animal model. In addition, we describe the signaling pathway related to senescence which p53, IGF-1 and SIRT1 play an important role in. Furthermore, autophagy is involved in the signaling pathway associated with aging. Several new compounds modulating the signaling pathway of senescence are introduced in this review. Here, we try to provide a new insight in the molecular basis for the aging mechanism and development of aging marker. In addition, the compounds introduced here could be available for pharmaceutical applications for the prevention and the treatment of diseases related to aging.

Inhibition of Inflammatory-cytokines Production and Prostaglandin E2 Activity by Puerariae Radix Extracts (갈근 추출물에 의한 염증성 Cytokine 생성 억제 및 Prostaglandin E2 활성 저해에 관한 연구)

  • Kim, Si-Na;Kim, Hee-Seok;Nam, Gyeong-Sug;Hwang, Sung-Wan;Hwang, Sung-Yeoun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.1
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    • pp.28-34
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    • 2006
  • The ethanol extracts of Puerariae Radix inhibited cyclooxygenase-2 (COX-2) activity in bone marrow derived mast cells (BMMC). COX-2 is responsible for the production of large amounts of proinflammatory prostaglandins (PGs) at the inflammatory site. We have investigated the anti-inflammatory effect of ethyl acetate fraction from $70\%$ ethanol extract of Puerariae Radix (EPR), and attempted acetic acid induced writhing to verify the analgesic effect. Inflammation was induced by interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a), $inteferon-\gamma$ $(IFN-\gamma)$ and lipopolysaccharide (LPS). EPR showed strong inhibitory efficacy against cytokine-induced proteoglycan degradation, prostaglandin $E_2\;(PGE_2)$ production, nitric oxide (NO) production, and matrix-metalloproteinases (MMPs) expression in mouse macrophage and rabbit articular chondrocyte. In the writhing test, EPR $(200\~400\;mg/kg)$ exhibited a dose-dependent inhibition of writhing. The results indicate that EPR have anti-inflammatory and analgesic activities, and could be a good herbal medicine candidate for treating of osteoarthritis (OA).

Effects of Autoclaved Morinda officinalis Root Extract on the Suppressive Efficacy of MMP-1 Enzyme (고온고압 처리된 파극천 추출물의 MMP-1 발현 억제 효능 증진)

  • Kang, Jung Wook;Oh, Jung Young;Bae, Jun Tae;Kim, Jin Hwa;Lee, Geun Soo;Pyo, Hyeong Bae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.1
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    • pp.35-43
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    • 2015
  • Morinda officinalis (Rubiaceae) is a medicinal herb that has traditionally been used for the treatment of skin inflammation. The present study was to investigate the inhibitory efficacy of matrix metalloproteinases-1 (MMP-1) of the extracts of the root of M. officinalis, which was autoclaved at $132^{\circ}C$ and $1.2kgf/cm^2$ for 15 min using an autoclave. The composition of the extracts were compared with that prepared without autoclaved treatment. Total phenol and flavonoid contents were analyzed for the autoclaved M. officinalis root extract (AME) and M. officinalis root extract (ME). Results showed that the autoclaved AME contained total phenol and flavonoid contents 1.5-fold times more than those from ME. AME showed DPPH and superoxide radical scavenging activities as 79.25% and 94.5%, respectively, at the concentration of $500{\mu}g/mL$. In anti-inflammatory assay, AME inhibited the activity of COX-2 and 5-LOX metabolites. In addition, AME showed higher an inhibition rate in MMP-1 expression than ME in UVA-irradiated human dermal fibroblast (HDF) without any significant cytotoxicity. UVB-induced cytotoxicity and cell death were effectively suppressed by AME. In conclusion, autoclaving the M. officinalis root increased the phenol and flavonoid contents. The extracts of the autoclaved M. officinalis enhanced the antioxidant, anti-inflammatory and anti-MMP-1 effects. Thus, the extracts could be an useful active ingredient in cosmetics.

Anti-invasion Effects of Calystegia soldanella Solvent Extracts and Partitioned Fractions on PMA-stimulated Fibrosarcoma Cells (갯메꽃 추출물과 유기용매 분획물의 암전이 억제 효과)

  • Son, Jaemin;Kim, Junse;Kim, Hojun;Seo, Youngwan
    • Journal of Life Science
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    • v.29 no.3
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    • pp.287-294
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    • 2019
  • Calystegia soldanella is distributed in coastal sand dunes and has high environmental adaptability; it is also known to be effective for anti-oxidant, anti-pyretic, anti-septic, and diuretic action. This study investigated the effect of crude extracts and organic solvent fractions of C. soldanella on MMP-2 and MMP-9 expression, MMP activity, and cell mobility in phorbol-12-myristate-13-acetate (PMA)-induced fibrosarcoma HT-1080 cells. C. soldanella was twice extracted, once with methylene chloride (MC) and once with methanol (MeOH). After the MC and MeOH extracts were combined, their suppressive effects on MMP-2 and MMP-9 expression, MMP enzymatic activity, and gene and protein expression were measured by gelatin zymography, enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction, and western blot method. Cell mobility for the HT-1080 cells was observed by wound healing assay. The combined crude extracts showed a significant suppressive effects on MMP-2 and MMP-9 expression. To explore active inhibitory elements, the combined extracts were fractionated according to polarity into with n-hexane, 85% aqueous methanol, n-butanol, and water. Across these four solvent fractions, MMP-2 and MMP-9 activity and cell mobility in the HT-1080 cells were all strongly inhibited by the n-hexane fraction. These results suggest that C. soldanella extract and organic solvent fractions could be used as potent MMP inhibitors for effective anti-cancer treatments to suppress cancer invasion and metastasis.

Protective effect of Artemisiae Capillaris Herba water extract on liver injury induced by thioacetamide (인진호 열수 추출물이 thioacetamide에 의해 유발된 간손상에 미치는 간보호 효과)

  • Kim, Min Ju;Lee, Jin A;Shin, Mi-Rae;Park, Hae-Jin;Roh, Seong-Soo
    • Journal of Nutrition and Health
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    • v.54 no.4
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    • pp.412-421
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    • 2021
  • Purpose: Thioacetamide (TAA) produces reactive oxygen species (ROS) in the liver, and the generated ROS induces liver injury through inflammatory reactions. The current study was undertaken to investigate the hepatoprotective effect of Artemisiae Capillaris Herba water extract (AC), imparted via its antioxidant activity, in an animal model of TAA-induced liver injury. Methods: Animal experiments were conducted in 5 groups: normal, control (TAA 200 mg/kg), SM (TAA 200 mg/kg + silymarin 100 mg/kg), ACL (TAA 200 mg/kg + AC 100 mg/kg), ACH (TAA 200 mg/kg + AC 200mg/kg). TAA (intraperitoneal) and treatment compounds (per oral) were administered for 3 days. Serum levels of ammonia concentration and myeloperoxidase (MPO) activity were subsequently measured. Liver tissues were subjected to western blot analysis for measuring the oxidative stress (NADPH oxidase), anti-oxidative activity (Nrf2, heme oxygenase-1 [HO-1], superoxide dismutase [SOD], catalase, and GPx-1/2), tissue inhibitors of metalloproteinase (TIMP)-1, and matrix metalloproteinases (MMPs) protein expressions. Results: Serum ammonia levels and MPO activity were significantly increased in the TAA-induced control group, whereas groups administered AC treatment showed markedly reduced levels. Western blot analysis revealed significantly increased NOX2 and p22phox expressions, (oxidative stress-related factors) in the TAA-induced control group. These levels were determined to be significantly decreased after AC exposure. Moreover, antioxidant-related factors including Nrf2, HO-1, SOD, catalase, and GPx-1/2 were significantly decreased in the control group and increased in the AC treated groups. In addition, MMP expressions were significantly suppressed in the AC treatment group due to increased levels of TIMP-1. Conclusion: Taken together, these data indicate that exposure to AC reduces the oxidative stress by inhibiting the expression of NADPH oxidase (NOX2 and p22phox) through the Nrf2 signaling pathway. We therefore propose the potential of AC for the prevention and treatment of TAA-induced liver injury.

Protective Effect of Dioscoreae Rhizoma Extracts in MIA-induced Rat. (MIA로 유발된 골관절염 동물모델에서 산약 추출물의 골관절염 개선 효과)

  • Kim, Min Ju;Park, Hae-Jin;Kim, Kyeong Jo;Lee, Jin A;Shin, Mi-Rae;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.34 no.4
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    • pp.27-35
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    • 2019
  • Objectives : Osteoarthritis is characterized by degeneration of articular cartilage, which is characterized by chronic pain, stiffness and decrease range of motion. The present study was designed to compare the therapeutic effect of Dioscoreae Rhizoma water extract (DRW) and Dioscoreae Rhizoma 30% ethanol extract (DRE) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : Osteoarthritis was induced by injection of MIA ($50{\mu}{\ell}$ with $80mg/m{\ell}$) into the knee joint cavity of rats. After adaptation period for seven days, rats were divided by 5 groups (n=10/group): normal group, control group, positive control (indomethacin 5 mg/kg), DRW 200 mg/kg treated group, DRE 200 mg/kg treated group (n=10/group). The hind paw weight distribution was measured with the changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$) in articulation tissue. Also, the cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factoralpha ($TNF{\alpha}$), interleukin-6 (IL-6), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated by western blot analysis. Results : The administration of DRW and DRE significantly decreased the hind paw weight distribution. The ROS and $ONOO^-$ levels of cartilaginous tissue were significantly decreased in DRW and DRE compared to control group. The results showed that DRE decreased inflammatory cytokines such as iNOS and $TNF{\alpha}$. Also DRE decreased MMP-1 and increased TIMP-1. Conclusions : Based on the above results, Dioscoreae Rhizoma extract seems to have the therapeutic effect on osteoarthritis via suppression of inflammation.

Improvement Effect of Corni Fructus 30% Ethanol Extract by MIA-Induced Osteoarthritis Animal Model (MIA로 골관절염 유발된 동물모델에서 산수유(山茱萸) 30% Ethanol 추출물의 개선 효과)

  • Kim, Min Ju;Lee, Jin A;Shin, Mi-Rae;Park, Hae-Jin;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.35 no.1
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    • pp.35-44
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    • 2020
  • Objectives : The objective of this study was to investigate the therapeutic effect of Corni Fructus 30% ethanol extract (CFE) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : The subjects were divided into 4 groups ; Normal group (N, n=10), MIA-induced osteoarthritis control group (Con, n=10), indomethacin 5 mg/kg treated group (INDO, n=10), CFE 200 mg/kg treated group (CFE, n=10). Blood and articulation tissues were collected after two weeks of drug administration. Oxidative stress was analyzed with reactive oxygen species (ROS), peroxynitrite (ONOO-). And the Nuclear factor erythroid-2 (Nrf2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, glutathione peroxidase-1/2 (GPx-1/2), Nuclear Factor Kappa B p65 (NF-κBp65), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), Interleukin 1β (IL-1β), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated by western blot. Results : The administration of CFE showed a significant reduction of changes in relative hind paw weight distribution. Reactive oxygen species (ROS) and peroxy nitrite (ONOO-) levels of articulation tissues were significantly decreased in CFE compared to the control group. Western blot measurements of Nrf2, HO-1, SOD, catalase, GPx-1/2 showed that the CFE group was increased compared to the Con group. And western blot measurements of NF-κBp65, COX-2, iNOS, TNFα, IL-6, IL-1β showed that the CFE group was reduced compared to the Con group. Also CFE group decreased MMP-1 and increased TIMP-1. Conclusion : Based on the above results, it can be seen that osteoarthritis is improved when Corni Fructus 30% ethanol extract treated.

Cordycepin Inhibits LPS-induced Cell Migration and Invasion in Human Colorectal Carcinoma HCT116 cells through Down-regulation of Prostaglandin E2-EP4 Receptor (LPS 유도된 HCT116 인간 대장암세포에서 cordycepin의 prostaglandin E2-EP4 receptor 감소 조절을 통한 세포의 이동과 전이 억제 효과)

  • Jung Eun Kim;Bo-Ram Kim;Su Hui Seong;Jin-Ho Kim;Ha-Nul Lee;Chan Seo;Ji Min Jung;Su A Im;Kyung-Min Choi;Jin-Woo Jeong
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2023.04a
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    • pp.50-50
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    • 2023
  • Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

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