• Title/Summary/Keyword: MMP-10

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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.

Effects of Fructus Amomi Amari, Eucommiae Cortex, Bombyx Batryticatus Extract on Improving Symptoms of Late-onset Hypogonadism (익지인(益智仁), 두충(杜沖), 백강잠(白殭蠶) 혼합추출물이 남성갱년기 증상 개선에 미치는 영향)

  • Park, Sun Young;Ahn, Sang Hyun;Kim, Ho Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.33 no.2
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    • pp.89-101
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    • 2019
  • In recent times, the number of men with late-onset hypogonadism has increased, and interest on this topic has also increased. This study was conducted to investigate effects of the mixture extract of Fructus amomi Amari, Eucommiae cortex, Bombyx batryticatus on improve late-onset hypogonadism. The experimental subjects consisted of three groups: a control group consisting of 8-week-old male ICR mice that had undergone no treatment, an aging-elicited group (AE group) consisting of 50-week-old ICR male mice that had undergone no treatment, and a Mixed herbal extract treatment group (MT group) consisting of 50-week-old ICR male mice that had undergone the mixture extract of Fructus amomi Amari, Eucommiae cortex, Bombyx batryticatus treatment (0.1 g/kg/day) for 6 months. After the experiment, the mice from all the experimental groups were dissected, and they were analyzed through histochemical and immunohistochemical methods. The mixture extract of Fructus amomi Amari, Eucommiae cortex, Bombyx batryticatus reduces aging-induced cell damage and oxidative stress and increases the secretion of serotonin and B-endorphin in aged mice, and promotes spermatogenesis in seminiferous tubules and reduces apoptosis and oxidative stress, and increases androgen receptor, $17{\beta}-HSD$ and GnRH, increases the ratio of smooth muscle to collagen fibers in the corpus cavernosum, increases eNOS, decreases PDE-5 and oxidative stress in aged mice, so it improves depression, reproductive, sexual problems caused by Late-onset hypogonadism. the mixture extract of Fructus amomi Amari, Eucommiae cortex, Bombyx batryticatus inhibits the induction of osteoporosis by increasing decreased bone matrix distribution due to aging, increasing the activities of OPC and OPN, which are produced in osteoblasts, and decreasing RANKL, MMP-3 activity, increasing OPG activity. It also reduces muscle damage, oxidative stress, inflammation and apoptosis of muscle tissue, and increases Myo-D in the sartorius muscle of aged mice for improving muscle atrophy caused by by Late-onset hypogonadism.

Ginsenosides Rk1 and Rg5 inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition and suppress migration, invasion, anoikis resistance, and development of stem-like features in lung cancer

  • Kim, Hyunhee;Choi, Pilju;Kim, Taejung;Kim, Youngseok;Song, Bong Geun;Park, Young-Tae;Choi, Seon-Jun;Yoon, Cheol Hee;Lim, Won-Chul;Ko, Hyeonseok;Ham, Jungyeob
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.134-148
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    • 2021
  • Background: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Panax ginseng Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF-β1) and self-renewal in A549 cells is relatively unknown. Methods: We treated TGF-β1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties. Results: EMT is induced by TGF-β1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-β1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-β1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-β1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells. Conclusions: Rk1 and Rg5 regulate the EMT inducing TGF-β1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

Korean Red Pine (Pinus densiflora) Bark Extract Attenuates Aβ-Induced Cognitive Impairment by Regulating Cholinergic Dysfunction and Neuroinflammation

  • Go, Min Ji;Kim, Jong Min;Kang, Jin Yong;Park, Seon Kyeong;Lee, Chang Jun;Kim, Min Ji;Lee, Hyo Rim;Kim, Tae Yoon;Joo, Seung Gyum;Kim, Dae-Ok;Heo, Ho Jin
    • Journal of Microbiology and Biotechnology
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    • v.32 no.9
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    • pp.1154-1167
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    • 2022
  • In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta1-42 (Aβ1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aβ-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aβ and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1β. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aβ1-42-induced cognitive impairment in mice.

Corni Fructus Inhibits Wrinkle Formation by Reduced Advanced glycation end product (AGEs) (산수유의 최종당화산물 억제로 인한 주름 개선효과)

  • Lee, AhReum;Kim, SooHyun;Kim, SuJi;Kim, KyeongJo;Kwon, Ojun;Choi, JoonYoung;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.32 no.5
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    • pp.1-6
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    • 2017
  • Objectives : Corni Fructus (CF) is traditional herbal medicine used on polyuria, low back pain, and tinnitus. This study aimed to evaluate inhibits skin wrinkle formation effect of CF. Methods : To evaluate the produce inhibition effect of CF, SD-rats were distributed into four groups; normal rats (Nor), AGEs (advenced glycation end product)-induced rats (Con), AGEs-induced rats treated with 100mg/kg CF (CF). To induce AGEs, streptozotocin (50mg/kg) was administered intraperitoneally and after 3 days oral administrated 100mM methyl glyoxal for 3 weeks. Results : The oral administration of CF suppressed the reactive oxygen specis (ROS) in serum. The AGEs in skin tissues was significantly reduced through treatment of CF. Furthermore, the expressions of AGEs related proteins such as polyclonal anti-$N^e$-(carboxymethyl)lysine (CML), anti-$N^e$-(carboxyethyl)lysine (CEL), AGE receptors (RAGE) were decreased in CF treated group compared with the control group in skin tissues. Inflammation-related proteins such as Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) reduced in CF treatment group than control group. AGE-induced rats exhibited that the significant decreased collagen however, CF treatment (100mg/kg of body weight) up regulated collagen by improved the expression levels of skin fibril-related genes such as Matrix metalloproteinase (MMP-1). Conclusion : Taken together, our study suggests that CF regulates ROS to prevent accumulation of AGEs and inhibits skin wrinkles. Our finding indicate that CF may be an effective agent for inhibits AGEs formation, and improved skin wrinkle.