• Title/Summary/Keyword: MMP-1 inhibition

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Effect of Antioxidation and Inhibition of Matrix Metalloproteinase-1 from Ligularia fischeri (곰취의 항산화와 UVA에 의한 MMP-1 발현 저해효과)

  • Na, Young;Kim, Jin-Hwa;Sim, Gwan-Sub;Lee, Bum-Chun;Pyo, Hyeong-Bae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.3 s.58
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    • pp.129-134
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    • 2006
  • In this study, we examined the effects of antioxidant, lipid peroxidation inhibition and suppression of UVA-induced MMP-1 expression in human dermal fibroblasts. Ligularia fischeri extract showed free radical scavenging effect by 82.3% at 5 mg/mL and superoxide radical scavenging effect by 79.3% at 5 mg/mL in the kanthine/xanthine oxidase system, respectively. At the concentration of $500{\mu}g/mL$, L. fischeri extract showed 97% inhibition on lipid peroxidation of linoleic acid. UVA induced MMP expression in human dermal fibroblasts was reduced 35% by treatment with $100{\mu}g/mL$ of L. fischeri extract. These results suggest that L. fischeri extract can be used for an anti-aging agent by antioxidation, lipid peroxidation inhibition and reducing UVA-induced MMP-1 production.

Cinnamic acid derivatives as potential matrix metalloproteinase-9 inhibitors: molecular docking and dynamics simulations

  • Mohammad Hossein Malekipour;Farzaneh Shirani;Shadi Moradi;Amir Taherkhani
    • Genomics & Informatics
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    • v.21 no.1
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    • pp.9.1-9.13
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    • 2023
  • Matrix metalloproteinase-9 (MMP-9) is a zinc and calcium-dependent proteolytic enzyme involved in extracellular matrix degradation. Overexpression of MMP-9 has been confirmed in several disorders, including cancers, Alzheimer's disease, autoimmune diseases, cardiovascular diseases, and dental caries. Therefore, MMP-9 inhibition is recommended as a therapeutic strategy for combating various diseases. Cinnamic acid derivatives have shown therapeutic effects in different cancers, Alzheimer's disease, cardiovascular diseases, and dental caries. A computational drug discovery approach was performed to evaluate the binding affinity of selected cinnamic acid derivatives to the MMP-9 active site. The stability of docked poses for top-ranked compounds was also examined. Twelve herbal cinnamic acid derivatives were tested for possible MMP-9 inhibition using the AutoDock 4.0 tool. The stability of the docked poses for the most potent MMP-9 inhibitors was assessed by molecular dynamics (MD) in 10 nanosecond simulations. Interactions between the best MMP-9 inhibitors in this study and residues incorporated in the MMP-9 active site were studied before and after MD simulations. Cynarin, chlorogenic acid, and rosmarinic acid revealed a considerable binding affinity to the MMP-9 catalytic domain (ΔGbinding < -10 kcal/ mol). The inhibition constant value for cynarin and chlorogenic acid were calculated at the picomolar scale and assigned as the most potent MMP-9 inhibitor from the cinnamic acid derivatives. The root-mean-square deviations for cynarin and chlorogenic acid were below 2 Å in the 10 ns simulation. Cynarin, chlorogenic acid, and rosmarinic acid might be considered drug candidates for MMP-9 inhibition.

The Effects of Paeonia Lactiflora Pallas on Inhibition of Oxygen Free Radical, Anti-inflammation and MMP-1 Inhibitory Activity (적작약 꽃 추출물의 활성산소 억제와 항염증 및 MMP-1 발현 억제능 효과에 관한 연구)

  • Leea, Jae-Nam;Kim, Young-Sam
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.3
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    • pp.797-806
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    • 2018
  • This study attempted to investigate the effects of Paeonia Lactiflora Pallas (P. lactiflora) on the inhibition of oxygen free radical, anti-inflammation and MMP-1 inhibitory activity and examine its possibility as a functional cosmetic material. For test methods, the inhibition of oxygen free radical after measuring reactive oxygen species (ROS) in the cell, cytotoxicity assessment and anti-inflammation were measured, and MMP-1 inhibitory effects in the HDF cell were measured. According to the test, the inhibition of ROS was confirmed in RAW 264.7 and HDF cells. In terms of cytotoxicity assessment, 90% or higher cell viability was detected at $5/10{\mu}g/mL$ Paeonia Lactiflora Pallas extract while it was 80% or higher at other concentration levels in both RAW 264.7 and HDF cells. In addition, NO production was inhibited in the RAW 264.7 cell while MMP-1 was significantly inhibited in the HDF cell. The above results reveal a possibility of Paeonia Lactiflora Pallas extract as a functional cosmetic material after confirming the inhibition of ROS synthesis in the cell, antioxidant and anti-inflammatory effects by inhibiting NO synthesis, low toxicity on skin cells and anti-aging effect through MMP-1 inhibition.

Essential Role for c-jun N-terminal Kinase on tPA-induced Matrix Metalloproteinase-9 Regulation in Rat Astrocytes

  • Lee, Sun-Ryung
    • Animal cells and systems
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    • v.10 no.2
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    • pp.79-83
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    • 2006
  • Tissue plasminogen activator (tPA) is used to lyse clots and reperfuse brain in ischemic stroke. However, sideeffects of intracerebral hemorrhage (ICH) and edema limit their clinical application. In part, these phenomena has been linked with elevations in matrix metalloproteinase-9 (MMP-9) in neurovascular unit. However little is known about their regulatory signaling pathways in brain cells. Here, I examine the role of MAP kinase pathways in tPA-induced MMP-9 regulation in rat cortical astrocytes. tPA $(1-10\;{\mu}g/ml)$ induced dose-dependent elevations in MMP-9 and MMP-2 in conditioned media. Although tPA increased phosphorylation in two MAP kinases (ERK, JNK), only inhibition of the JNK pathway by the JNK inhibitor SP600126 significantly reduced MMP-9 upregulation. Neither ERK inhibition with U0126 nor p38 inhibition with SB203580 had any significant effects. Taken together, these results suggest that c-jun N-terminal kinase (JNK) plays an essential role for tPA-induced MMP-9 upregulation.

Anti-microbial, Anti-inflammatory and Anti-oxidative Effects of Herbal Medicine Extracts as Anti-gingivitis Ingredients (치주 질환 예방 및 치료용 소재로서 수종의 생약성분 추출물에 관한 항균, 항염, 항산화 효능 연구)

  • Lee, Dong-Jae;Han, Il-Min;Kim, Woo-Jung;Cho, In-Sik
    • Journal of dental hygiene science
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    • v.10 no.1
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    • pp.25-29
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    • 2010
  • This study was to estimate the effect of herbal medicines on periodontal disease. To screen effective materials for periodontal disease, we performed a series of test for 15 herbal medicine extracts. MIC test for P. gingivalis, IL-$1{\alpha}$ inhibition test, MMP-1 inhibition test and SOD activation test were carried out for herbal medicine extracts, respectively. The results are as followings : 1) Eunhang, Youkdoogu, Daewhang, Hoobak, Goojulcho, Yongacho, Mokhyang, Sesin, Sancho and Hoehyang extracts were effective for reduce P. gingivalis, 2) Eunhang, Jacyak, Youkdoogu, Hagocho, Hoobak, Guaru and Sanyak extracts showed high IL-$1{\alpha}$ inhibition rates, 3) Eunhang and Youkdoogu extracts have effects on MMP-1 inhibition, 4) Eunhang, Sanyak and Youkdoogu extracts effectively activate SOD. Especially, Eunhang extract has high performance through all estimations and can effectively prevent and treat periodontal disease.

The Anti-wrinkle Effects and Whitening Effects of Galla Rhois (오배자의 항 주름 효과 및 미백 효과에 미치는 실험적 연구)

  • Park, Jin-Mee;Park, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.1
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    • pp.135-148
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    • 2010
  • Recently, the demands for the effective and safe depigmentating and anti-aging agents of the skin have increased due to the medical, pharmaceutical and cosmetic reasons. The aim of this study is to search Galla Rhois (GR) inhibitory activity against aging process of skin in vitro. GR was screened for their inhibitory activity against elastase. GR (final concentration 1 mg/ml) appeared over 40% of inhibition of elastase activity. So we investigated anti wrinkle effects of GR look through MMP-1 inhibition activity. Also Extracts of GR showed higher anti-tyrosinase activity than arbutin (final concentration 1 mg/ml). These results suggest that GR could be potential sources of anti-aging and whitening effects for the skin. Objective : Galla Rhois extracts, Elastase (pancreatic from porcine pancreas), N-Succinyl-(Ala)3-p-nitroanilide, Ursolic acid, mushroom tyrosinase, L-tyrosine, arbutin, Amicon Ultra, Hand Hold UV lamp, MMP-1 primary antibody, MMP-1 secondary antibody Result : 1. GR appeared over 40% of elastase inhibitory activity. 2. GR had MMP-1 inhibition activity. 3. GR showed higher anti-tyrosinase activity than arbutin. Conclusion : According to above results, it is supposed that Galla Rhois could be strong potential sources of anti-aging and whitening effects for the skin.

Inhibition of MMP-1 Expression and Collagen Synthesis Activity of Ultrasonication Processed Ginseng Flower Buds Extract (초음파 처리 인삼화뢰 추출물의 콜라겐 합성작용 및 MMP-1 발현저해)

  • Kim, Shin Jung;Nam, Yun Min;Kim, Yong Min;Ko, Sung Kwon
    • Korean Journal of Pharmacognosy
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    • v.46 no.2
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    • pp.154-159
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    • 2015
  • This study was to evaluate the effect of isopropyl alcohol fraction of ultrasonication processed ginseng flower buds(GFB-IF) on the collagen synthesis activity and inhibition of MMP-1 suppression in UV-irradiated human dermal fibroblasts. The higher contents of ginsenoside Rg2(8.234%), Rh1(5.749%), F4(3.881%) in isopropyl alcohol fraction of ginseng flower buds obtained by ultrasonication process at 600W(100℃) for 16 hours. GFB-IF had collagen synthesis effect. GFB-IF induced a significant dose-dependent decrease in the expression for MMP-1 protein. These results suggest that GFB-IF is a potential candidate for the prevention and treatment of wrinkle improving.

Inhibition of Matrix Metalloproteinases-12 (MMP-12) and Anti-oxidant Effect of Xanthohumol from Hop (Humulus lupulus L.)

  • Lee, Keyong Ho;Yoon, Won Ho
    • Natural Product Sciences
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    • v.18 no.4
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    • pp.261-265
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    • 2012
  • Xanthohumol was isolated from hops (Humulus lupulus L.), and then investigated anti-oxidant effect by AAPH-induced LLC-PK1 cell and oxygen radical absorbance capacity (ORCA) assays and MMP-12 inhibitory effect by direct MMP-12 inhibition assay. The treatment of xanthohumol protected LLC-PK1 cells from AAPH-induced cell damage such as cell viability, SOD and GSH-px reduction in a dose dependant manner (0.1, 1, and $5{\mu}M$), the SOD value was 2.98, 4.51, and 5.77 U/mg protein, and GSH-px value was 30.12, 49.32, and 60.11 U/mg protein. ORAC value of xanthohumol was showed as 4320, 12004, and $14209{\mu}M$ TE/g at the concentration 0.1, 1, and $5{\mu}M$, respectively. The change of SOD and GSH-px values was significantly correlated with the results of ORAC assay, that is, AAPH-induced cell and ORCA assays. In addition, inhibition of MMP-12 that is known to play an important role in skin aging was 14%, 37%, 46%, and 79% at the concentration of 0.01, 0.1, 1, and $5{\mu}M$, respectively. On the basis of these results, xanthohumol from hops (Humulus lupulus L.) showed interesting biological and pharmacological activity such as anti-oxidant effect and anti-aging.

The effect of L-carnitine in the expression of matrix metalloproteinases by human dermal fibroblasts

  • Yoon, Eun-Jeong;Lee, Kyoung-Eun;Sim, Kwan-Sup;Lee, Bum-Chun;Pyo, Hyeong-Bae;Choe, Tae-boo
    • Proceedings of the SCSK Conference
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    • 2003.09b
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    • pp.12-25
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    • 2003
  • L-camitine ($\beta$ -hydroxy-${\gamma}$ -trimethyl-ammoniumbutyric acid) is a small water-soluble molecule important in mammalian fat metabolism. It is essential for the normal oxidation of fatty acids by the mitochondria, and is involved in the trans-esterification and excretion of acyl-CoA esters. In this paper, to investigate the relationship between aging and L-camitine, we investigated the effects of in vitro MMP inhibition and activity and expression of UVA-induced MMP 1 in human skin fibroblasts. Fluorometric assays of the proteolytic activities of MMP-l were performed using fluorescent collagen substrates. ELISA (enzyme linked immuno sorbent assay), gelatin-substrate zymography, and RT-PCR ELISA techniques were used for the effects of L-camitine on MMP expression and activity, MMP mRNA expression in UVA irradiated fibroblast. L-camitine inhibited the activities of MMP-l in a dose-dependent manner and the $IC_{50}$/ values calculated from semi-log plots were 2.45mM, and L-carnitine showed strong inhibition on MMP-2 (gelatinase) activity in UVA irradiated fibroblast by zymography. Also, UVA induced MMP expression was reduced 40% by treated with L-carnitine, and MMP-l mRNA expression was reduced dose-dependent manner. Therefore L-carnitine was able to significantly inhibition the MMP activity, regulation of MMP expression in protein and mRNA level. All these results suggest that L-carnitine may be useful as new anti-aging cofactor for protection against UVA induced MMP expression and activity.

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Baicalin suppresses lipopolysaccharide-induced matrix metalloproteinase expression: action via the mitogen-activated protein kinase and nuclear factor κB-related protein signaling pathway

  • Ko, Seon-Yle
    • International Journal of Oral Biology
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    • v.46 no.1
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    • pp.51-59
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    • 2021
  • Periodontal disease is an inflammatory disease that affects the destruction of the bone supporting the tooth and connective tissues surrounding it. Periodontal ligament fibroblasts (PDLFs) induce overexpression of matrix metalloproteinase (MMP) involved in periodontal disease's inflammatory destruction. Osteoclasts take part in physiological bone remodeling, but they are also involved in bone destruction in many kinds of bone diseases, including osteoporosis and periodontal disease. This study examined the effect of baicalin on proteolytic enzymes' production and secretion of inflammatory cytokines in PDLFs and RAW 264.7 cells under the lipopolysaccharide (LPS)-induced inflammatory conditions. Baicalin inhibited the expression of the protein, MMP-1 and MMP-2, without affecting PDLFs' cell viability, suggesting its possibility because of the inhibition of phosphorylation activation of mitogen-activated protein kinase's p38, and the signal transduction process of nuclear factor κB (NFκB)-related protein. Also, baicalin reduced the expression of MMP-8 and MMP-9 in RAW 264.7 cells. This reduction is thought to be due to the inhibition of the signal transduction process of NFκB-related proteins affected by inhibiting p65RelA phosphorylation. Also, baicalin inhibited the secretion of nitric oxide and interleukin-6 induced by LPS in RAW 264.7 cells. These results suggest that baicalin inhibits connective tissue destruction in periodontal disease. The inhibition of periodontal tissue destruction may be a therapeutic strategy for treating inflammatory periodontal-diseased patients.