• Title/Summary/Keyword: MMP-2 activity

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Effects of salmon DNA fraction in vitro and in a monosodium iodoacetate-induced osteoarthritis rat model

  • Ra, Ho Jong;Oh, Mi Young;Kim, Hee Ju;Lee, Seung Yong;Eom, Dae Woon;Lee, Suk Kyu;Kim, Su-Nam;Chung, Kyu Sung;Jang, Hyuk Jai
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.163-172
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    • 2018
  • PRF001 is a fragmented DNA polymer extracted from the testes of salmon. The purpose of this study was to assess the anti-inflammatory effect of PRF001 in vitro as well as the protective effect of PRF001 intake against arthritis in a rat model. In vitro, cell survival and inflammatory markers after $H_2O_2$ treatment to induce cell damage were investigated in CHON-001 cells treated with different concentrations of PRF001. In vivo, osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA) into the knee joints of rats. After consumption of PRF001 (10, 50, or 100 mg/kg) for 4 weeks, inflammatory mediators and cytokines in articular cartilage were investigated. In vitro, the levels of inflammatory markers, $IL-1{\beta}$, $TNF-{\alpha}$, COX-2, iNOS, and PGE2, were significantly suppressed by PRF001 treatment. In vivo, the inflammatory mediators and cytokines, $IL-1{\beta}$, p-Erk1/2, $NF-{\kappa}B$, $TNF-{\alpha}$, COX-2, and PGE2, as well as MMP3 and MMP7, which have catabolic activity in chondrocytes, were decreased in the MIA-induced osteoarthritic rats following intake of PRF001. Histological analysis revealed that PRF001 had a protective effect on the articular cartilage. Altogether, these results demonstrated that the anti-inflammatory property of PRF001 contributes to its protective effects in osteoarthritis through deregulating $IL-1{\beta}$, $TNF-{\alpha}$, and subsequent signals, such as p-Erk1/2, $NF-{\kappa}B$, COX-2, PGE2, and MMPs.

Effects of Sotosaja-hwan on the Generation of ROS, RNS, and on the Expression of NF-${\kappa}B$-dependent Proteins in ob/ob Mouse (소도사자환이 ob/ob mouse에서 ROS/ RNS 생성 억제 및 NF-${\kappa}B$ 의존성 단백질에 미치는 영향)

  • Bang, Yong-Suk;Jeong, Ji-Cheon
    • The Journal of Korean Medicine
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    • v.30 no.1
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    • pp.51-63
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    • 2009
  • Objectives: 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 $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: 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 standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-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 blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan 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 PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

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Analgesic Effect and Inhibition of Prostaglandin $E_2$ Activity and Pro-inflammatory Cytokines Production by Ethyl Alcohol Extract from New Herbal Formula (신규 생약 복합추출물에 의한 Prostaglandin $E_2$ 활성억제, 염증성 Cytokine 생성 저해 및 진통 작용에 관한 연구)

  • Kwon, Soon-Yong;Lee, Hwa-Sung;Lee, Soon-Hyuck;Im, Gun-Il;Kim, Si-Na;Kim, Hee-Seok;Hwang, Sung-Wan;Hwang, Sung-Yeoun
    • Korean Journal of Pharmacognosy
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    • v.37 no.3
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    • pp.136-142
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    • 2006
  • New herbal formula (NHF) is the ethanol extract mixture of Puerariae radix, Artemisia capillaries and Perilla frutescens. We have Investigated the effects on anti-inflammation by NHF and attempted acetic acid induced writhing to verify the analgesic effect. Macrophages and chondrocytes were obtained from mouse and rabbit. Inflammation was induced bγ interleukin-1, tumor necrosis $factor-{\alpha}$, $interferon-{\gamma}$, and lipopolysaccharide. NHF showed strong inhibitory efficacy against cytokine-induced proteoglycan degradation, $PGE_2$ production, NO production, and MMP-9 expression in rabbit articular chondrocyte. In the writhing test, NHF exhibited a dose-dependent inhibition of writhing. Futhermore, NHF increased the activity of SOD. NHF have anti-inflammatory and analgesic activities, and could be a good herbal medicine candidate for curing of osteoarthritis.

Hepato-Protective Activities of Jasminum officinale L. var. grandiflorum Aqueous Extract via Activation of AMPK in HepG2 Cells (AMPK 활성화를 통한 소형화(素馨花) (Jasminum officinale L. var. grandiflorum) 열수 추출물의 HepG2 간세포 보호 활성)

  • Sang Mi Park;Dae Hwa Jung;Byung Gu Min;Kyung Hwan Jegal;Sung Hui Byun;Jae Kwang Kim;Sang Chan Kim
    • Herbal Formula Science
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    • v.31 no.4
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    • pp.231-243
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    • 2023
  • Objectives : Jasminum officinale L. var. grandiflorum is used as a traditional or folk remedy in China to treat arthritis, hepatitis, duodenitis, conjunctivitis, gastritis, and diarrhea. In this study, we aimed to study the hepatocyte protective activity and molecular mechanism of Jasminum officinale L. var. grandiflorum aqueous extract (JGW) using HepG2 hepatocyte cell lines. Methods : HepG2 cells were pretreated with diverse concentrations of JGW, and then the cells were exposed to tert-butyl hydroperoxide (tBHP) for inducing oxidative stress. Hydrogen peroxide (H2O2) production, glutathione (GSH) concentration, mitochondrial membrane potential (MMP) and cell viability were measured to investigate hepato-protective effects of JGW. Phosphorylation of AMP-activated protein kinases (AMPK), acetyl coenzyme A carboxylase (ACC) and effects of compound C on cell viability were examined to observe the role of AMPK on JGW-mediated cytoprotection. Results : Pretreatment with JGW (10-300 ㎍/mL) significantly suppressed cytotoxicity induced by tBHP in a concentration dependent manner and reduced the expression of cleaved PARP and cleaved caspase-3 proteins related to apoptosis in HepG2 cells. In addition, pretreatment with JGW significantly prevented the increase in H2O2 production, GSH depletion, and lower MMP induced by tBHP. Treatment with JGW (30 minutes of incubation and concentrations of 100 and 300 ㎍/mL) increased the phosphorylation of AMPK and ACC and treatment with compound C, a chemical inhibitor of AMPK, inhibited the cytoprotective effect of JGW. Conclusions : Our results demonstrated that JGW may protect hepatocytes from oxidative stress via activation of AMPK.

Epigallocatechin-3-gallate Inhibits Tax-dependent Activation of Nuclear Factor Kappa B and of Matrix Metalloproteinase 9 in Human T-cell Lymphotropic Virus-1 Positive Leukemia Cells

  • Harakeh, Steve;Diab-Assaf, Mona;Azar, Rania;Hassan, Hani Mutlak Abdulla;Tayeb, Safwan;Abou-El-Ardat, Khalil;Damanhouri, Ghazi Abdullah;Qadri, Ishtiaq;Abuzenadah, Adel;Chaudhary, Adeel;Kumosani, Taha;Niedzwiecki, Aleksandra;Rath, Mathias;Yacoub, Haitham;Azhar, Esam;Barbour, Elie
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1219-1225
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    • 2014
  • Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol molecule from green tea and is known to exhibit antioxidative as well as tumor suppressing activity. In order to examine EGCG tumor invasion and suppressing activity against adult T-cell leukemia (ATL), two HTLV-1 positive leukemia cells (HuT-102 and C91-PL) were treated with non-cytotoxic concentrations of EGCG for 2 and 4 days. Proliferation was significantly inhibited by 100 ${\mu}M$ at 4 days, with low cell lysis or cytotoxicity. HTLV-1 oncoprotein (Tax) expression in HuT-102 and C91-PL cells was inhibited by 25 ${\mu}M$ and 125 ${\mu}M$ respectively. The same concentrations of EGCG inhibited NF-kB nuclearization and stimulation of matrix metalloproteinase-9 (MMP-9) expression in both cell lines. These results indicate that EGCG can inhibit proliferation and reduce the invasive potential of HTLV-1-positive leukemia cells. It apparently exerted its effects by suppressing Tax expression, manifested by inhibiting the activation of NF-kB pathway and induction of MMP-9 transcription in HTLV-1 positive cells.

Induction of apoptotic cell death in human bladder cancer cells by ethanol extract of Zanthoxylum schinifolium leaf, through ROS-dependent inactivation of the PI3K/Akt signaling pathway

  • Park, Cheol;Choi, Eun Ok;Hwangbo, Hyun;Lee, Hyesook;Jeong, Jin-Woo;Han, Min Ho;Moon, Sung-Kwon;Yun, Seok Joong;Kim, Wun-Jae;Kim, Gi-Young;Hwang, Hye-Jin;Choi, Yung Hyun
    • Nutrition Research and Practice
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    • v.16 no.3
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    • pp.330-343
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    • 2022
  • BACKGROUND/OBJECTIVES: Zanthoxylum schinifolium is traditionally used as a spice for cooking in East Asian countries. This study was undertaken to evaluate the anti-proliferative potential of ethanol extracts of Z. schinifolium leaves (EEZS) against human bladder cancer T24 cells. MATERIALS/METHODS: Subsequent to measuring the cytotoxicity of EEZS, the anti-cancer activity was measured by assessing apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). In addition, we determined the underlying mechanism of EEZS-induced apoptosis through various assays, including Western blot analysis. RESULTS: EEZS treatment concentration-dependently inhibited T24 cell survival, which is associated with apoptosis induction. Exposure to EEZS induced the expression of Fas and Fas-ligand, activated caspases, and subsequently resulted to cleavage of poly (ADP-ribose) polymerase. EEZS also enhanced the expression of cytochrome c in the cytoplasm by suppressing MMP, following increase in the ratio of Bax:Bcl-2 expression and truncation of Bid. However, EEZS-mediated growth inhibition and apoptosis were significantly diminished by a pan-caspase inhibitor. Moreover, EEZS inhibited activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and the apoptosis-inducing potential of EEZS was promoted in the presence of PI3K/Akt inhibitor. In addition, EEZS enhanced the production of ROS, whereas N-acetyl cysteine (NAC), a ROS scavenger, markedly suppressed growth inhibition and inactivation of the PI3K/Akt signaling pathway induced by EEZS. Furthermore, NAC significantly attenuated the EEZS-induced apoptosis and reduction of cell viability. CONCLUSIONS: Taken together, our results indicate that exposure to EEZS exhibits anti-cancer activity in T24 bladder cancer cells through ROS-dependent induction of apoptosis and inactivation of the PI3K/Akt signaling pathway.

In Vitro Cytotoxicity, Skin Regeneration, Anti-wrinkle, Whitening and In Vivo Skin Moisturizing Effects of Oncheongeum (온청음 물 추출물의 세포독성, 피부재생, 주름개선, 미백 및 보습 효과)

  • An, Tteul-E-Bom;Kim, Dong-Chul
    • The Journal of Korean Obstetrics and Gynecology
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    • v.29 no.1
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    • pp.14-34
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    • 2016
  • Objectives: The objective of this study was to evaluate the effects of cytotoxicity, skin regeneration, anti-wrinkle, whitening and skin moisturizing of Oncheongeum (OCE).Methods: The cytotoxicity of OCE lyophilized aqueous extracts (yield=13.82%) was observed against human normal fibroblast cells and B16/F10 murine melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium Bromide (MTT) assay, and skin regeneration and anti-wrinkle effects were also evaluated through the assay of collagen type I synthesis compared to the transformation of the growth factor (TGF)-β1, hyaluronidase, collagenase and matrix metalloproteinase (MMP)-1 inhibitory assays compared to oleanolic acid (OA), and elastase inhibitory effects compared to phosphoramidon disodium salt (PP). In addition, OCE’s whitening effects were measured by a tyrosinase inhibitory assay and melanin formation test in B16/F10 murine melanoma cells compared to arbutin, and skin moisturizing effects were observed through a mouse skin water content test, respectively. Results: No OCE treatment-related cytotoxic effects appeared on human normal fibroblasts and B16/F10 murine melanoma cells. OCE concentration-dependently increased the collagen Type I synthesis on human normal fibroblast cells, and also effectively inhibited hyaluronidase, elastase, collagenase and MMP-1 activities. In addition, OCE inhibited melanin production of B16/F10 murine melanoma cells and activity of tyrosinase. And significant and dose-dependent increases of skin water content were detected in OCE-treated mouse skin compared to vehicle control skins. Conclusions: OCE showed favorable and sufficient effects in skin regeneration, anti-wrinkle, whitening and skin moisturizing in this experiment. But more detail mechanisms and studies on the skin protective efficiency of in vivo are needed with the screening of active biological compounds in individual OCE herbs.

First Evidence that Sika Deer (Cervus nippon) Velvet Antler Extract Suppresses Migration of Human Prostate Cancer Cells

  • Tang, YuJiao;Jeon, Byong-Tae;Wang, Yanmei;Choi, Eun-Ju;Kim, Yon-Suk;Hwang, Jin-Woo;Park, Pyo-Jam;Moon, Sang Ho;Kim, Eun-Kyung
    • Food Science of Animal Resources
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    • v.35 no.4
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    • pp.507-514
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    • 2015
  • Deer velvet antler (DVA) is one of the most popular medicines in China. Numerous studies have demonstrated that velvet antler possess biological effects. However, data regarding its anti-migration activity on prostate cancer is scarce. In this study, we investigated the inhibitory effect of top DVA (T-DVA) on the expression of prostate-specific antigen (PSA) and migration-related genes in the human prostate cancer cell, LNCaP. The T-DVA down-regulated the expression of PSA. In addition, the RadiusTM assay revealed that T-DVA inhibited the migration behavior of prostate cancer cells. Furthermore, the expression of matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) was also decreased with T-DVA. On the contrary, T-DVA increased the tissue inhibition of metallo-proteinase (TIMP)-1 and (TIMP)-2. Taken together, our findings indicate that the T-DVA possesses anti-migration activity on prostate cancer cells. This is the first study of DVA to report the anti-migration activity on prostate cancer.

BIOLOGICAL ACTIVITES OF PLANT LEAF EXTRACTS; AVAILABILITY OF STAR FRUIT LEAF EXTRACT AGAINST SKIN AGING

  • Yoshihito Kawashima;Zhou, Yan-Yang;Naoko Kishida;Nobuaki Ohto;Daisuke Araho;Yoko Ito;Toshimitsu Kambara;Zhou, Wan-Hua
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.645-658
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    • 2003
  • We evaluated activities of various plant leaf extracts and found the availability against skin aging in the leaf extract of star fruit (Averrhoa carambola L), and developed Star Fruit Leaf Extract BG30 as an ingredient of cosmetics. Star Fruit Leaf Extract BG30 was found to show scavenging activities of reactive oxygen species and an inhibitory effect on the activity of matrix metalloproteinase-1. It showed increasing activity of type I collagen and recovery effect from damage of UV-B irradiation in human fibroblast. We performed the separation of the active principal from Star Fruit Leaf Extract BG30 to give isofurcatin 2"-Ο-$\alpha$-L-rhamnopyranoside, which showed increasing activity of type I collagen. To examine the anti-wrinkle effect of Star Fruit Leaf Extract BG30, seven volunteers applied a Star Fruit Leaf Extract BG30 1 % cream in double blind manner to one-side of the corner of their eye and the placebo cream to the opposite side. Clinical evaluation of wrinkling was performed every week for 5 weeks using a silicone rubber replica. A statistically significant improvement of Star Fruit Leaf Extract BG30-treated site was seen in decreased wrinkles. Star Fruit Leaf Extract BG30 results in clinically visible improvement in wrinkling when used topically for 5 weeks.

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Effects of Ginsenoside-$Rg_1$ on Post-thawed Miniature Pig Sperm Motility, Mitochondria Activity, and Membrane Integrity

  • Hwang, You Jin;Kim, Dae Young
    • Journal of Embryo Transfer
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    • v.28 no.1
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    • pp.63-71
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    • 2013
  • In this study, we used flow a cytometric assay to evaluate plasma membrane integrity and mitochondrial activity in post-thawed sperm that was supplemented with ginsenoside-$Rg_1$. Varying concentrations of ginsenoside-$Rg_1$ (0, 25, 50 and $100{\mu}M/ml$) were used in the extender during cryopreservation to protect the DNA of thawed sperm, thereby increasing the viability and motility rate as evaluated using a computer-assisted sperm analysis (CASA) method. The results derived from CASA were used to compare the fresh, control, and ginsenoside-$Rg_1$ groups. Sperm motility and the number of progressively motile sperm were significantly (p<0.05) higher in the $50{\mu}M/ml$ ginsenoside-Rg1 group ($61.0{\pm}4.65%$) than in the control ($46.6{\pm}7.02%$), $25{\mu}M/ml$ ($46.2{\pm}4.76%$), and $100{\mu}M/ml$ ginsenoside-$Rg_1$ ($52.0{\pm}1.90%$) groups. However, the velocity distribution of post-thawed sperm did not differ significantly. Membrane integrity and MMP staining as revealed using flow cytometry were significantly (p<0.05) higher ($91.6{\pm}0.82%$) in the $50{\mu}M/ml$ ginsenoside-$Rg_1$ group than in the other groups. Here, we report that ginsenoside-$Rg_1$ affects the motility and viability of boar spermatozoa. Moreover, ginsenoside-$Rg_1$ can be used as a protective additive for the suppression of intracellular mitochondrial oxidative stress caused by cryopreservation.