• Title/Summary/Keyword: MMP-10

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Anti-proliferative Effects of Celastrol, A Quinine Methide Triterpene Extracted from the Perennial Vine Tripterygium wilfordii, on Obesity-related Cancers (미역줄나무 뿌리 추출물인 셀라스트롤의 비만관련 암증식 억제효과)

  • Park, Sunmi;Moon, Hyun-Seuk
    • Journal of Food Hygiene and Safety
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    • v.31 no.1
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    • pp.59-66
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    • 2016
  • It has been generally accepted that obesity and overweight are associated with metabolic diseases and cancer incidence. In fact, obesity increased risks of cancers i.e. breast, liver, pancreatic and prostate. Celastrol is a pentacyclic triterpenoid isolated from Thunder god vine, was used as a Chinese traditional medicine for treatment of inflammatory disorders such as arthritis, lupus erythematosus and Alzheimer's disease. Also, celastrol has various biological properties of chemo-preventive, neuro-protective, and anti-oxidant effects. Recent studies demonstrated that celastrol has anti-proliferation effects in different type of obesity-related cancers and suppresses tumor progression and metastasis. Anticancer effects of celastrol include regulation of $NF-{\kappa}B$, heat shock protein, JNK, VEGF, CXCR4, Akt/mTOR, MMP-9 and so on. For these reasons, celastrol has shown to be a promising anti-tumor agent. In this review, we will address the anticancer activities and multiple mechanisms of celastrol in obesity-related cancers.

Ameliorative effect of onion (Allium Cepa L.) flesh and peel on amyloid-β-induced cognitive dysfunction via mitochondrial activation (미토콘드리아 활성화를 통한 양파(Allium Cepa L.) 과육 및 과피의 Amyloid-β 유도성 인지손상에 대한 개선효과)

  • Park, Seon Kyeong;Lee, Uk;Kang, Jin Yong;Kim, Jong Min;Shin, Eun Jin;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.52 no.3
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    • pp.263-273
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    • 2020
  • In this study, in order to confirm the ameliorative effects of onion (Allium cepa L.) flesh and peel on amyloidbeta (Aβ)-induced cognitive dysfunction, we evaluated their in vitro neuroprotection and in vivo cognitive functions. As the result of in vitro neuroprotection, the protective effect of the ethyl acetate fraction of onion flesh (EOF) on Aβ-induced cytotoxicity was similar to that of the ethyl acetate fraction of onion peel (EOP). In the behavioral tests, the EOF and EOP effectively improved the Aβ-induced learning and memory impairments. For this reason, it could be concluded that the EOF and EOP improved the antioxidant activities (superoxide dismutase, oxidized glutathione/total glutathione, and malondialdehyde) in brain tissue. In addition, the EOF and EOP effectively activated mitochondrial functions by protecting the mitochondrial membrane potential, ATP, mitochondria-mediated protein (BAX and cytochrome c), and caspase 3/7 activities. The EOF and EOP also improved the cholinergic system (acetylcholinesterase and acetylcholine). Therefore, we suggest that onion could be used for management of Aβ-induced cognitive dysfunction.

The Sanguinarine Apoptosis Induction of Hep3B Human Hepatocellular Carcinoma Cells is Dependent on the Activation of Caspase (Sanguinarine에 의한 Hep3B 인체 간암세포의 apoptosis 유도에 관한 연구)

  • Han, Min Ho;Choi, Sung Hyun;Hong, Su Hyun;Park, Dong Il;Choi, ung Hyun
    • Journal of Life Science
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    • v.27 no.11
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    • pp.1340-1348
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    • 2017
  • Sanguinarine is a benzophenanthridine alkaloid derived from the roots of Sanguinaria canadensis L., which is used for the purpose of treating various diseases. Although studies of anticancer activities have been performed using various cancer cell lines, the phenomenon of inducing apoptosis in cancer cells by using sanguinarine requires more research. Therefore, this study investigated the anti-cancer activities and related mechanisms of sanguinarine used with Hep3B human hepatocellular carcinoma cells in terms of the regulation of apoptosis. Sanguinarine inhibited the proliferation of Hep3B cells in a concentration-dependent manner, which was associated with the induction of apoptosis. Sanguinarine also increased the activity of caspase-3, which is a typical effector caspase, and the activities of caspase-8 and caspase-9, which are key when initiating extrinsic and intrinsic apoptosis pathways, respectively. In addition, sanguinarine increased the expression of death receptor-related genes and pro-apoptotic BAX, which belongs to the Bcl-2 family, while suppressing the expression of anti-apoptotic Bcl-2. Sanguinarine promoted the truncation of Bid and enhanced the release of cytochrome c from the mitochondria to the cytoplasm due to a loss of mitochondrial membrane potential. Furthermore, the reduction of a survival rate that was induced by sanguinarine and the induction of apoptosis disappeared with the inhibition of artificial caspase activity. Therefore, the results of the study indicated that sanguinarine-induced apoptosis in Hep3B cells involves both extrinsic and intrinsic pathways; such apoptosis is a caspase-dependent phenomenon.

Apoptotic Cell Death of Human Leukemia U937 Cells by Essential Oil purified from Schisandrae Semen (오미자 종자 정유에 의한 인체백혈병 U937 세포의 apoptosis 유도)

  • Choi, Yung Hyun
    • Journal of Life Science
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    • v.25 no.2
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    • pp.249-255
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    • 2015
  • Schisandrae fructus [Schizandra chinensis (Turcz.) Baillon] is a medicinal herb widely used for treating various inflammatory and immune diseases in East Asian countries. The Schisandrae Semen essential oil (SSeo) from this plant has pharmacological activities, including antioxidant, antimicrobial, and antitumoral activities. Nevertheless, the biological activities and underlying molecular mechanisms of the potential anti-cancer effects of this oil remain unclear. In the present study, we investigated the potential inhibition of apoptosis signaling pathways by SSeo in human leukemia U937 cells and evaluated the underlying molecular mechanism. Exposure to SSeo resulted in a concentration-dependent growth inhibition due to apoptosis, which was verified by DNA fragmentation, the presence of apoptotic bodies, and an increase in the sub-G1 ratio. Induction of apoptotic cell death by SSeo was correlated with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family (including X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and surviving) and anti-apoptotic Bcl-2, and with up-regulation of death receptor (DR) 4 and DR5, depending on dosage. SSeo treatment also induced Bid truncation, mitochondrial dysfunction, proteolytic activation of caspase-3, -8 and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase. Taken together, these findings suggest that SSeo may be a potential chemotherapeutic agent for use in the control of human leukemia cells. Further studies are needed to identify its active compounds.

Induction of Apoptosis in Human Colon Carcinoma HCT116 Cells Using a Water Extract of Lepidium virginicum L. (콩다닥냉이 추출물에 의한 HCT116 대장암세포의 사멸 유도에 관한 연구)

  • Chae, Yang-Hui;Shin, Dong-Yeok;Park, Cheol;Lee, Yong-Tae;Moon, Sung-Gi;Choi, Yung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.5
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    • pp.649-659
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    • 2011
  • To examine the anti-cancer effects of Lepidium virginicum L., the anti-proliferative and pro-apoptotic effects of a water extract of L. virginicum leaves (WELVL) and of L. virginicum roots (WELVR) were investigated in HCT116 human colon carcinoma cells. The treatment of HCT116 cells with WELVL and WELVR resulted in the inhibition of growth and morphological changes in a concentration-dependent manner by inducing apoptosis. The growth inhibition and apoptosis induction by WELVR was stronger than that of WELVL thus, we determined that WELVR was the more optimal extract for this study. The increased apoptotic events in HCT116 cells caused by WELVR were associated with an up-regulation of Fas ligand, Bax, and Bad expression, a down-regulation of Bcl-2, Bcl-$_XL$, and Bid expression, and a decrease in the mitochondrial membrane potential (MMP, ${\Delta}{\psi}m$). WELVR treatment induced the proteolytic activation of caspase-3, -8, and -9, and the degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase (PARP), ${\beta}$-catenin, and phospholipase C-${\gamma}1$ (PLC-${\gamma}1$). In addition, apoptotic cell death induced by WELVR was correlated with a down-regulation of inhibitors of the apoptosis protein (IAP) family, such as the X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and cIAP-2. These findings suggest that the WELVR-induced inhibition of cell proliferation is associated with the induction of apoptotic cell death. WELVR may be a potential chemotherapeutic agent for the control of HCT116 human colon carcinoma cells.

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).

Association of a Methanol Extract of Rheum undulatum L. Mediated Cell Death in AGS Cells with an Intrinsic Apoptotic Pathway

  • Hong, Noo Ri;Park, Hyun Soo;Ahn, Tae Seok;Jung, Myeong Ho;Kim, Byung Joo
    • Journal of Pharmacopuncture
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    • v.18 no.2
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    • pp.26-32
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    • 2015
  • Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying concentrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at $70{\mu}g/mL$, 15.94% at $140{\mu}g/mL$, 26.56% at $210{\mu}g/mL$ and 38.08% at $280{\mu}g/mL$). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.

Inhibitory Effect of Rosa multiflora hip Extract on UVB-induced Skin Photoaging in Hs68 Fibroblasts (자외선으로 유도된 Hs68 섬유아세포의 노화 반응에 대한 영실추출물의 억제 효능)

  • Park, Ji-Eun;Kim, Hyoung Ja;Kim, Su-Nam;Kang, Seung Hyun;Kim, Youn Joon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.4
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    • pp.351-359
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    • 2015
  • Acute and chronic ultraviolet (UV) irradiation triggers severe skin photoaging processes, which directly disrupt the normal three-dimensional integrity of skin. UV light stimulates the expression of matrix metalloproteinases (MMPs) which degrade constituents of extracellular matrix (ECM) proteins. These MMPs reduce collagen synthesis and decrease skin elasticity and integrity, resulting in wrinkle formation. In this study, we identified Rosa multiflora hip extract (RME) as an effective anti-photoaging ingredient. First, cell proliferation activity of RME was verified using Hs68 human dermal fibroblast cell line. RME downregulated MMPs expression through the inhibition of activator protein (AP)-1. In addition, type I and IV collagen expressions were increased with RME treatment and UVB-induced inflammatory responses were also reduced after RME treatment. In conclusion, R. multiflora hip extract may effectively improve UVB-induced skin aging and wrinkle formation which may provide as an anti-aging, anti-wrinkle, and anti-inflammation ingredient in cosmetic industry.

Stillbirth rates and their association with swine leucocyte antigen class II haplotypes in Microminipigs

  • Imaeda, Noriaki;Ando, Asako;Matsubara, Tatsuya;Takasu, Masaki;Nishii, Naohito;Miyamoto, Asuka;Ohshima, Shino;Kametani, Yoshie;Suzuki, Shingo;Shiina, Takashi;Ono, Tetsushi;Kulski, Jerzy K.;Kitagawa, Hitoshi
    • Animal Bioscience
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    • v.34 no.11
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    • pp.1749-1756
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    • 2021
  • Objective: Microminipig (MMP) is a miniature pig with an extra small body size for experimental use. In the present study, the occurrence of stillbirths and their genetic association with swine leukocyte antigen (SLA) class II haplotypes were evaluated in a population of MMPs. Methods: The occurrences of stillbirth and genetic association with SLA class II haplotypes using 483 stillborn and 2,246 live piglets, and their parents were compared among the three groups of newborn piglet litters; an all stillborn (AS) group consisting of only stillborn piglet litters, a partial stillborn (PS) group consisting of stillborn and live piglet litters, and an all alive (AA) group consisting of only live piglet litters. Results: The incidence of stillborn piglets was 483/2,729 (17.7%). Distributions of litter sizes, numbers of stillborn piglets in a litter, parities, and gestation periods were distinct among the three groups. The frequencies of low resolution haplotype (Lr)-0.7 or Lr-0.23 were higher in the AS group than in the PS or AA groups. In sires, the frequency of Lr-0.7 associated with the AS group was significantly higher in the AS group than with the AA group. In dams, the frequency of Lr-0.23 was significantly higher in the AS group than in the PS or AA groups, whereas the frequency of Lr-0.7 was not significantly different. Conclusion: The incidence of stillborn piglets in MMPs appears to be higher than those in other pig breeds. Several traits related with stillbirths such as the number of stillborn piglets and parities of the AS group were different from those of the PS and AA groups. Specific SLA class II haplotypes were associated significantly with a high incidence of stillbirths and could be used as genetic markers to adopt breeding strategies to lower the rate of stillbirth in MMPs.

Non-enzymatic softening of Calendula officinalis L. petals and its anti-skin aging effect for food materialization (식품소재화를 위한 Calendula officinalis L. 꽃잎의 항피부노화 기능성 규명 및 비효소적 연화 기술 연구)

  • Lim, Seokwon;Choi, Sungbin;Lee, Pomjoo;Kim, Hyung-sup;Lee, Da-young;Byun, Sanguine
    • Korean Journal of Food Science and Technology
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    • v.51 no.3
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    • pp.243-247
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    • 2019
  • Calendula (Calendula officinalis L.) petals are edible flowers which have been used as a decorative ingredient in dishes or as a medicinal food. In this study, the anti-skin aging potential of calendula petals was investigated. Additionally, the texture was softened by non-enzymatic methods to broaden their application as a food or cosmetic agent. Treatment of calendula prevented ultraviolet-induced matrix metalloproteinase-1 expression in skin cells. We investigated whether heating-based processing could soften calendula petals. The results from the punctual test demonstrated significant changes in the hardness of calendula petals depending on the pH, heating temperature, and time. Although there were minor differences among various processing conditions, the largest alteration in hardness was observed when the petals were softened by incubation at $80^{\circ}C$ and pH 2.3 for 120 min. Collectively, these results show that the application of proper processing conditions can soften calendula petals without using enzymes.