• Title/Summary/Keyword: MMP-12

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Methyl Linderone Suppresses TPA-Stimulated IL-8 and MMP-9 Expression Via the ERK/STAT3 Pathway in MCF-7 Breast Cancer Cells

  • Yoon, Jae-Hwan;Pham, Thu-Huyen;Lee, Jintak;Lee, Jiyon;Ryu, Hyung-Won;Oh, Sei-Ryang;Oh, Jae-Wook;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.30 no.3
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    • pp.325-332
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    • 2020
  • Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects of ML on the metastasis of human breast cancer cells. We used 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated MCF-7 cells as the cell model to study the effects of ML on invasion and migration. ML was found to reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Moreover, it inhibited two metastasis-related factors, matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8), at the mRNA and protein expression levels, in TPA-treated MCF-7 cells. The mechanism by which ML exerted these effects was through the inhibition of translocation of activator protein-1 (AP-1) and signal transducer and activator of transcription-3 (STAT3), mediated via phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, our findings indicated that ML attenuated the TPA-stimulated invasion and migration of MCF-7 cells by suppressing the phosphorylation of ERK and its downstream factors, AP-1 and STAT3. Therefore, ML is a potential agent for the treatment of breast cancer metastasis.

Effect of Cheongawongagam Extract on the Ovariectomized Rat Model of Osteoporosis (청아원가감 추출물이 난소적출로 유발된 흰쥐의 골다공증 모델이 미치는 영향)

  • Yun, Gee Won;Lee, Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.34 no.1
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    • pp.14-23
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    • 2020
  • This study was conducted to evaluate the efficacy of Cheongawongagam on osteoporosis rat. A total of 35 rats were divided into seven groups; Normal control(SD-Nr), experimental control group(OVX-CTL), positive control group(OVX-17β-E2) and herb extracts group[Eucommia ulmoides(OVX-EU-E), Juglandis semen(OVX-JR-SE), Acanthopanax senticosus(OVX-AS-E) extract and Cheongawongagam extracts(OVX-JAEG-E)]. All control group, and herb extracts group were ovariectomized. After the 3 weeks recovery period, herb extract group were orally administered 200 mg / kg of the EU-E, JR-SE, AS-E and JAEG-E for 12 weeks. In the OVX-CTL, 17β-estradiol(E2) was administered subcutaneously on the back of the rats at a dose of 0.03 ug/sc. Their body weight, serum total cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Leukotriene B4 (LTB4), calcium (Ca), estradiol, osteocalcin, and deoxypyridinoline (DPD) concentration were measured. Also, we investigated mRNA expression of inflammatory cytokine, MMP-2, MMP-9, and bone tissue. As a result, total cholesterol was significantly decreased in the OVX-AS-E and OVX-JAEG-E. ALP was significantly increased and osteocalcin, DPD was significantly decreased in OVX-JAEG-E. The expression of inflammatory mediators (TNF-α, IL-1β, LTB4, COX-2, NOS-2), inflammatory cytokines IL-1β and MMP-9 mRNA were significantly decreased in OVX-JAEG-E. Histologic examination of the femur showed that bone mineral density, and bone mass were increased and bone marrow were decreased in the OVX-JAEG-E group. The above experiment shows that cheongawongagam extract were effective in the prevention and treatment of osteoporosis.

Effects of Porcine Placenta Extract Ingestion on Ultraviolet B-induced Skin Damage in Hairless Mice

  • Hong, Ki-Bae;Park, Yooheon;Kim, Jae Hwan;Kim, Jin Man;Suh, Hyung Joo
    • Food Science of Animal Resources
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    • v.35 no.3
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    • pp.413-420
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    • 2015
  • The aim of our study was to evaluate the potential benefits of an oral supplement containing porcine placenta extract (PPE) on skin parameters related to cutaneous physiology and aging. PPEs were administered orally to hairless mice for 12 wk. The effects of oral PPE administration on skin water-holding capacity and Transepidermal Water Loss (TEWL) were similar to those of oral collagen (HYCPU2) administered as a positive control. Magnified photographs and replica images showed a reduction in UVB-induced wrinkle formation after collagen and PPE treatments. PPE treatments ameliorated the thicker skin surface that results from UVB exposure, based on a histological examination of skin tissue. The groups that were orally administered PPE (0.05%, OL; 0.1%, OH group) showed significantly reduced Matrix Metaloproteinase-2 (MMP-2) mRNA expression levels compared with the UVB control (Con), by 33.5% and 35.2%, respectively. The mRNA expression of another collagen-degrading protein, MMP-9, was also significantly lower in the groups that received oral administration of PPE (especially in the OH group) than in the control group. Additionally, oral administration of PPE significantly upregulated tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2 mRNA expression levels compared with expression levels in the control group (p<0.05). This indicates that orally administered PPE activated the expression of Timp-1 and -2, inhibitors of MMP, which is responsible for collagen degradation in skin. Taken together, we propose that long-term oral administration of PPE might have a beneficial effect with respect to skin photo-aging.

Study on the Anti-aging Activity of Gentianae sino-ornata Ethanol Extract (용담화 에탄올 추출물의 항노화 작용 연구)

  • Choi, Hyung-Wook;Li, Shun-Hua;Kim, Eun-Joo;Kim, Soo-Kyung;Lee, Jang-Cheon;Lim, Kyu-Sang
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.28 no.2
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    • pp.1-12
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    • 2015
  • Objective : The goal of this study is to identify the effects of extract ofGentianae sino-ornata(GSO) on the anti-oxidative activity of skin.For this purpose, several functions of GSO were analyzed in terms of skin-lightening activity and wrinkle improvement. Methods : Cell viability was measured by neutral red (NR) assay, and GSO showed highly efficacy in DPPH radical scavenging activity. The level of tyrosinase and matrix metalloproteinase-1 (MMP-1) in media was analyzed by ELISA kit, and the expressions of p-JNK and p-ERK was measured by Western blot. To elucidate inhibitory effects of GSO on melanin synthesis, I determined the tyrosinase activity and melanin production in B16F10 cells. Results : MMP-1 production in UVB-stimulated HDF cells was inhibited by GSO treatments, and also GSO inhibited protein expression levels of p-JNK and p-ERK. GSO significantly reduced tyrosinase activity and melanin synthesis in B16F10 cells. Conclusions : From these results, GSO appears to be effective on skin elasticity increase, wrinkle improvement, whitening as anti-aging activity.

Compound K attenuates stromal cell-derived growth factor 1 (SDF-1)-induced migration of C6 glioma cells

  • Kim, Hyuck;Roh, Hyo Sun;Kim, Jai Eun;Park, Sun Dong;Park, Won Hwan;Moon, Jin-Young
    • Nutrition Research and Practice
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    • v.10 no.3
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    • pp.259-264
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    • 2016
  • BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established. MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C $(PKC){\alpha}$ and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis. RESULTS: CK significantly reduced the phosphorylation of $PKC{\alpha}$ and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions. CONCLUSIONS: CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including $PKC{\alpha}$, ERK1/2, and MMPs.

UV Protection and Whitening Effects of Collagen Isolated from Outer Layer of the Squid Todarodes pacificus (동해 오징어 (Todarodes pacificus) 껍질 유래 콜라겐의 UV 보호능 및 미백효과)

  • Kwon, Min-Chul;Qadir, Syed Abdul;Kim, Hyo-Sung;Ahn, Ju-Hee;Cho, Nam-Hyun;Lee, Hyeon-Yong
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.41 no.1
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    • pp.7-12
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    • 2008
  • To develop a whitening agent, cytotoxicity of the soluble collagen isolated from Todarodes pacificus (CIT) was evaluated. CIT tested for cytotoxicity on human dermal fibroblast (CCD-986sk) was exhibited very low cytotoxicity. Because tyrosinase is the key enzyme for melanin biosynthesis, the use of various tyrosinase inhibitors is a common practice for whitening purpose in cosmetics. Tyrosinase inhibitory activity and melanin production assay were measured to confirm the whitening effect. The inhibitory effect of MMP-1 in UV-irradiated human dermal fibroblast was also performed. CIT showed strong inhibition potency on tyrosinase by 51.5% at 0.2 mg/mL which increased the inhibition by increasing the concentration of CIT, and showed 69.1% inhibition at 1.0 mg/mL. CIT showed strong inhibition effect on melanin production with 82% at 1.0 mg/mL. The CIT also reduced about 76% expression of MMP-1 in UV-irradiated CCD-986sk cell at 1.0 mg/mL. From the preliminary observations, we suggest that the collagen isolated from CIT could be a potential source of natural skin-whitening and anti-aging agents for the photo-damaged skin.

Protective Effect of KR-31378 on Oxidative Stress in Cardiac Myocytes

  • Kim Mi-Young;Lee Sunkyung;Yi Kyu Yang;Yoo Sung Eun;Lee Dong-Ha;Lim Hong;Kim Ho Soon;Lee Soo Hwan;Baik Eun Joo;Moon Chang-Hyun;Jung Yi-Sook
    • Archives of Pharmacal Research
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    • v.28 no.12
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    • pp.1358-1364
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    • 2005
  • In this study, we investigated whether a novel anti-ischemic $K_{ATP}$ opener KR-31378 [(2S,3S,4R)­N'-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2 -methly-2-dimethoxymethly-2H-benzopyran-4-yl)­N'-benzylguanidine] has protective effect against oxidative stress-induced death in heart-derived H9c2 cells. Cell death was induced by BSO, butionine sulfoximine, which inhibits GSH synthesis and subsequently increases reactive oxygen species (ROS) level. Cell death was quantitatively determined by measuring lactate dehydrogenase (LDH) activity and stained by Hoechst 33258. BSO-induced ROS production and mitochondrial membrane potential (MMP) were measured using 2',7'-dichlorofluorescein diacetate oxidation and rhodamine 123, respectively. Both the LDH release and the ROS elevation induced by treatment of H9c2 cells with 10 mM BSO, were significantly decreased by KR-31378. These protective effect and antioxidant effect of KR-31378 appeared to be independent on $K_{ATP}$ channel opening. Cells exposed to BSO showed an early reduction in MMP, and this reduction in MMP was significantly reversed by treatment with KR-31378. Caspase-3 activity in BSO treated H9c2 cells was remarkably increased, and this increased caspase-3 activity was significantly reversed by KR-31378. In conclusion, our results suggest that KR-31378 can produce cardioprotective effect against oxidative stress-induced cell death through antioxidant mechanism.

Anti-aging and Anti-oxidative Effect of Naesohwangryun-tang(NSHRT) (내소황련탕(內疎黃連湯)의 항노화 및 항산화 효능 연구)

  • Oh, Sol-Ra;Nam, Sang-Woo;Song, Young-Chae;Kim, Hee-Taek;Kim, Yong-Min;Lee, Chun-Il
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.34 no.4
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    • pp.12-23
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    • 2021
  • Objectives : This study is to investigate the anti-aging and antioxidant effects of Naesohwangryeon-tang(NSHRT) extract in Hs68 fibroblasts. Methods : The fibroblast cell line Hs68 cells were used and MTT analysis was performed to measure the cell viability of Naesohwangryeon-tang, and then MMP-1 was induced with the cytokine TNF-𝛼 to confirm the anti-aging effect through real-time PCR and ELISA. In addition, ROS was induced with the TNF-𝛼 to confirm the anti-oxidant effect through DCF-DA. The signaling pathway according to the antioxidant effect was performed by western blot. Results : Naesohwangryeon-tang did not show cytotoxicity at all concentrations(100-800㎍/㎖) treated on Hs68 cells, and the inhibitory effect of MMP-1 was also confirmed. In addition, it was confirmed that the intracellular ROS increased by TNF-α was decreased by Naesohwangryeon-tang, and it was confirmed that the expression of NQO1 was increased in a concentration-dependent manner of Naesohwangryeon-tang. Conclusions : These results suggest that Naesohwangryeon-tang can be used as an anti-aging material by demonstrating the anti-aging and antioxidant effects of Naesohwangryeon-tang.

Development of a new mini straw for cryopreservation of boar semen

  • Almubarak, Areeg;Osman, Rana;Lee, Seongju;Yu, Iljeoung;Jeon, Yubyeol
    • Journal of Animal Reproduction and Biotechnology
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    • v.37 no.2
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    • pp.113-120
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    • 2022
  • Sperm cryopreservation is a fundamental process for the long-term conservation of livestock genetic resources. Yet, the packaging method has been shown, among other factors, to affect the frozen-thawed (FT) sperm quality. This study aimed to develop a new mini-straw for sperm cryopreservation. In addition, the kinematic patterns, viability, acrosome integrity, and mitochondrial membrane potential (MMP) of boar spermatozoa frozen in the developed 0.25 mL straw, 0.25 mL (minitube, Germany), or 0.5 mL (IMV technologies, France) straws were assessed. Post-thaw kinematic parameters were not different (experiment 1: total motility (33.89%, 32.42%), progressive motility (19.13%, 19.09%), curvilinear velocity (42.32, 42.86), and average path velocity (33.40, 33.62) for minitube and the developed straws, respectively. Further, the viability (38.56%, 34.03%), acrosome integrity (53.38%, 48.88%), MMP (42.32%, 36.71%) of spermatozoa frozen using both straw were not differ statistically (p > 0.05). In experiment two, the quality parameters for semen frozen in the developed straw were compared with the 0.5 mL IMV straw. The total motility (41.26%, 39.1%), progressive motility (24.62%, 23.25%), curvilinear velocity (46.44, 48.25), and average path velocity (37.98, 39.12), respectively, for IMV and the developed straw, did not differ statistically. Additionally, there was no significant difference in the viability (39.60%, 33.17%), acrosome integrity (46.23%, 43.23%), and MMP (39.66, 32.51) for IMV and the developed straw, respectively. These results validate the safety and efficiency of the developed straw and highlight its great potential for clinical application. Moreover, both 0.25 mL and 0.5 mL straws fit the present protocol for cryopreservation of boar spermatozoa.

A Comparative Study of Rose Hip Extracts on Osteoarthritis in Cartilage Cells (In vitro 실험모델에서 생산지에 따른 로즈힙 추출물의 골관절염 억제효과 비교 연구)

  • Nam, Da-Eun;Lee, Min-Jae;Kang, Namgil;Park, Geumduck;Lee, Jeongmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.12
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    • pp.1663-1670
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    • 2012
  • The inhibitory effects of rose hip (Rosa canina L.) water extracts from two different manufactures on osteoarthritis was comparatively investigated in primary cultures of rat cartilage cells. To identify the effects of rose hip extracts against $H_2O_2$ (300 ${\mu}M$, 2 hr) treatment, cell survival was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell survival increased by rose hip extracts in the range of 100 to 600 ${\mu}g/mL$ of $H_2O_2$ treatment. To determine the anti-inflammatory effects of rose hip extracts, tumor necrosis factor alpha (TNF-${\alpha}$), nitric oxide (NO), and Cox-2 expression were measured after lipopolysaccharide (LPS) activation. TNF-${\alpha}$ level with rose hip extract treatment was decreased by 27.4% and 31.9% at 600 ${\mu}g/mL$ of $H_2O_2$ treatment. Nitric oxide was inhibited by rose hip extract at 100~600 ${\mu}g/mL$ of $H_2O_2$ treatment in a dose-dependent manner. In addition, Cox-2 protein expression was dose-dependently decreased while Cox-1 had no change in expression level. The severity of osteoarthritis is controlled by a balance between anabolic and catobolic factors in an articulation, therefore the expression of these factors plays a critical role in preventing osteoarthritis. In measuring anabolic factors, the genetic expression of collagen type I increased with rose hip treatment, while the genetic expression of collagen II did not change. In addition, the genetic expression of aggrecan (proteoglycan core protein) was significantly increased. while the genetic expression of matrix metalloproteinase (MMP) 3, 7 and 13, known catabolic factors, was significantly inhibited by treatment with rose hip extract. The expression of MMP13 was especially highly influenced. In conclusion, rose hip water extracts show inhibitory effects on cell death by $H_2O_2$ mediated oxidative stress, which is related to inhibitory effects on inflammation due to TNF-${\alpha}$, NO, and Cox-2. The ability of rose hip extracts to ameliorate inflammation in primary cultures of cartilage cells seems to associate with an increased genetic expression of specific anabolic factors, collagen type I and aggrecan, and a decreased expression of catabolic factors, MMPs (3, 7, and 13). However, there were no significant differences between rose hip extracts from the two manufacturers.