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    18β-Glycyrrhetinic acid가 lipopolysaccharide에 의한 생쥐 뇌조직의 염증성 사이토카인과 해마신경세포 자연사에 미치는 영향 = Effects of 18β-glycyrrhetinic acid on pro-inflammatory cytokines and neuronal apoptosis in the hippocampus of lipopolysaccharide-treated mice

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    https://www.riss.kr/link?id=A102393216

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    Objectives : 18β-Glycyrrhetinic acid (18betaGA) is an metabolite of glycyrrhizin in Glycyrrhiza (licorice). The present study investigated anti-inflammatory and anti-apoptosis effect of 18betaGA on the brain tissue of lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : 18betaGA was administered orally with low (30 ㎎/㎏) and high (100 ㎎/㎏) doses for 3 days prior to LPS (3 ㎎/㎏) injection. Pro-inflammatory cytokines mRNA including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and inflammatory enzyme cyclooxygenase-2 (COX-2) mRNA were measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Histological changes of Cornu ammonis area 1 (CA1) neurons, Bax, Bcl-2, and caspase-3 expression in the hippocampus was also evaluated by immunohistochemistry and Western blotting method. Results : 18betaGA significantly attenuated the up-regulation of TNF-α, IL-1β, IL-6 mRNA, and COX-2 mRNA expression in the brain tissues induced by the LPS injection. 18betaGA also significantly attenuated the reductions of the thickness of CA1 and the number of CA1 neurons. The up-regulation of Bax protein expression in the hippocampal tissue by the LPS injection was significantly attenuated, while the ratio of Bcl-2/Bax expression was increased by 18betaGA treatment. 18betaGA also significantly attenuated the up-regulation of Bax and caspase-3 expression in the CA1 of the hippocampus. Conclusion : This results indicate that 18betaGA has anti-inflammatory and anti-apoptosis effect under neuroinflammation induced by the LPS injection and suggest that 18betaGA may be a beneficial drug for various brain diseases accompanied with the brain tissue inflammation.
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    Objectives : 18β-Glycyrrhetinic acid (18betaGA) is an metabolite of glycyrrhizin in Glycyrrhiza (licorice). The present study investigated anti-inflammatory and anti-apoptosis effect of 18betaGA on the brain tissue of lipopolysaccharide (LPS)-treated...

    Objectives : 18β-Glycyrrhetinic acid (18betaGA) is an metabolite of glycyrrhizin in Glycyrrhiza (licorice). The present study investigated anti-inflammatory and anti-apoptosis effect of 18betaGA on the brain tissue of lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : 18betaGA was administered orally with low (30 ㎎/㎏) and high (100 ㎎/㎏) doses for 3 days prior to LPS (3 ㎎/㎏) injection. Pro-inflammatory cytokines mRNA including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and inflammatory enzyme cyclooxygenase-2 (COX-2) mRNA were measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Histological changes of Cornu ammonis area 1 (CA1) neurons, Bax, Bcl-2, and caspase-3 expression in the hippocampus was also evaluated by immunohistochemistry and Western blotting method. Results : 18betaGA significantly attenuated the up-regulation of TNF-α, IL-1β, IL-6 mRNA, and COX-2 mRNA expression in the brain tissues induced by the LPS injection. 18betaGA also significantly attenuated the reductions of the thickness of CA1 and the number of CA1 neurons. The up-regulation of Bax protein expression in the hippocampal tissue by the LPS injection was significantly attenuated, while the ratio of Bcl-2/Bax expression was increased by 18betaGA treatment. 18betaGA also significantly attenuated the up-regulation of Bax and caspase-3 expression in the CA1 of the hippocampus. Conclusion : This results indicate that 18betaGA has anti-inflammatory and anti-apoptosis effect under neuroinflammation induced by the LPS injection and suggest that 18betaGA may be a beneficial drug for various brain diseases accompanied with the brain tissue inflammation.

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    참고문헌 (Reference)

    1 Liu T, "Tumor necrosis factor-alpha expression in ischemic neurons" 25 : 1481-1488, 1994

    2 Campbell IL, "Transgenic models to study the actions of cytokines in the central nervous system" 5 : 126-135, 1998

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    4 Pollack M, "The role of apoptosis in the normal aging brain, skeletal muscle, and heart" 959 : 93-107, 2002

    5 Oztanir MN, "The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model" 35 : 1221-1228, 2014

    6 Wang L, "The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb" 5 : 310-315, 2015

    7 Akman T, "The Neuroprotective effect of glycyrrhizic acid on an experimental model of focal cerebral ischemia in rats" 38 : 1581-1588, 2015

    8 Aid S, "Targeting cyclooxygenases-1 and -2 in neuroinflammation: Therapeutic implications" 93 : 46-51, 2011

    9 Mizoguchi K, "Specific binding and characteristics of 18β-glycyrrhetinic acid in rat brain" 9 : e95760-, 2014

    10 Jiang Y, "Prevention of constitutive TNF receptor 1 signaling by silencer of death domains" 283 : 543-546, 1999

    1 Liu T, "Tumor necrosis factor-alpha expression in ischemic neurons" 25 : 1481-1488, 1994

    2 Campbell IL, "Transgenic models to study the actions of cytokines in the central nervous system" 5 : 126-135, 1998

    3 Dunn AJ, "The role of cytokines in infection-related behavior" 840 : 577-585, 1998

    4 Pollack M, "The role of apoptosis in the normal aging brain, skeletal muscle, and heart" 959 : 93-107, 2002

    5 Oztanir MN, "The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model" 35 : 1221-1228, 2014

    6 Wang L, "The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb" 5 : 310-315, 2015

    7 Akman T, "The Neuroprotective effect of glycyrrhizic acid on an experimental model of focal cerebral ischemia in rats" 38 : 1581-1588, 2015

    8 Aid S, "Targeting cyclooxygenases-1 and -2 in neuroinflammation: Therapeutic implications" 93 : 46-51, 2011

    9 Mizoguchi K, "Specific binding and characteristics of 18β-glycyrrhetinic acid in rat brain" 9 : e95760-, 2014

    10 Jiang Y, "Prevention of constitutive TNF receptor 1 signaling by silencer of death domains" 283 : 543-546, 1999

    11 Hossein Hosseinzadeh, "Pharmacological Effects of Glycyrrhiza spp. and Its Bioactive Constituents: Update and Review" Wiley-Blackwell 29 (29): 1868-1886, 2015

    12 Hwang IK, "Neuroprotective effects of roasted licorice, not raw form, on neuronal injury in gerbil hippocampus after transient forebrain ischemia" 27 : 959-965, 2006

    13 Harry GJ, "Neuroinflammation and microglia:considerations and approaches for neurotoxicity assessment" 4 : 1265-1277, 2008

    14 Sternberg EM, "Neural-immune interactions in health and disease" 100 : 2641-2647, 1997

    15 Jacotot E, "Mitochondrial membrane permeabilization during the apoptotic process" 887 : 18-30, 1999

    16 Griffin WST, "Microglial interleukin-1βexpression in human head injury: Correlation with neuronal and neuritic β-amyloid precursor protein expression" 176 : 133-136, 1994

    17 Kawakami Z, "Isoliquiritigenin is a novel NMDA receptor antagonist in kampo medicine yokukansan" 31 : 1203-1212, 2011

    18 Ishida T, "Inhibitory effects of glycyrrhetinic Acid on DNA polymerase and inflammatory activities" 2012 : 650514-, 2012

    19 Rivest S, "How the blood talks to the brain parenchyma and the paraventricular nucleus of the hypothalamus during systemic inflammatory and infectious stimuli" 223 : 22-38, 2000

    20 Luo L, "Glycyrrhizin suppresses HMGB1 inductions in the hippocampus and subsequent accumulation in serum of a kainic acid-induced seizure mouse model" 34 : 987-997, 2014

    21 Zhang J, "Glycyrrhizin protects brain against ischemiareperfusion injury in mice through HMGB1-TLR4-IL-17A signaling pathway" 1582 : 176-186, 2014

    22 Lidan Luo, "Glycyrrhizin Attenuates Kainic Acid-Induced Neuronal Cell Death in the Mouse Hippocampus" 한국뇌신경과학회 22 (22): 107-115, 2013

    23 Wang CY, "Glycyrrhizic acid and 18β-glycyrrhetinic acid modulate lipopolysaccharide-induced inflammatory response by suppression of NF-κB through PI3K p110δand p110γinhibitions" 59 : 7726-7733, 2011

    24 Kao TC, "Glycyrrhizic acid and 18beta-glycyrrhetinic acid inhibit inflammation via PI3K/Akt/GSK3beta signaling and glucocorticoid receptor activation" 58 : 8623-8629, 2010

    25 Kim SR, "Glycyrrhetinic acid inhibits Porphyromonas gingivalis lipopolysaccharide-induced vascular permeability via the suppression of interleukin-8" 62 : 145-154, 2013

    26 Cacquevel M, "Cytokines in neuroinflammation and Alzheimer's disease" 5 : 529-534, 2004

    27 Szelényi J, "Cytokines and the central nervous system" 54 : 329-338, 2001

    28 Kronfol Z, "Cytokines and the brain: implications for clinical psychiatry" 157 : 683-694, 2000

    29 Minghetti L, "Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases" 63 : 901-910, 2004

    30 Rosenberg PB, "Clinical aspects of inflammation in Alzheimer's disease" 17 : 503-514, 2005

    31 Whiteley W, "Blood markers for the prognosis of ischemic stroke: a systematic review" 40 : e380-e389, 2009

    32 Gross A, "Bcl-2family members and the mitochondria in apoptosis" 13 : 1899-1911, 1999

    33 Gibson ME, "BAX contributes to apoptotic-like death following neonatal hypoxia-ischemia: evidence for distinct apoptosis pathways" 7 : 644-655, 2001

    34 Nagata S, "Apoptotic DNA fragmentation" 256 : 12-18, 2000

    35 Tatton WG, "Apoptosis in Parkinson's disease: signals for neuronal degradation" 53 : S61-S72, 2003

    36 Zhou J, "18β-glycyrrhetinic acid suppresses experimental autoimmune encephalomyelitis through inhibition of microglia activation and promotion of remyelination" 5 : 13713-, 2015

    37 Kim ME, "18β-Glycyrrhetinic acid from licorice root impairs dendritic cells maturation and Th1 immune responses" 35 : 329-335, 2013

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    연월일 이력구분 이력상세 등재구분
    2026 평가 재인증평가 신청대상 (재인증)
    2020-01-01 등재 등재학술지 유지 (재인증) KCI등재
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    기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
    2016 0.57 0.57 0.54
    KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
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