Paeoniflorin inhibits tributyltin chloride-induced apoptosis in hypothalamic neurons via inhibition of MKK4-JNK signaling pathway
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Paeoniflorin inhibits tributyltin chloride-induced apoptosis in hypothalamic neurons via inhibition of MKK4-JNK signaling pathway. / Cong, Chao; Kluwe, Lan; Li, Shengnan; Liu, Xiaofei; Liu, Yang; Liu, Huicong; Gui, Wenjia; Liu, Te; Xu, Lianwei.
in: J ETHNOPHARMACOL, Jahrgang 237, 12.06.2019, S. 1-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Paeoniflorin inhibits tributyltin chloride-induced apoptosis in hypothalamic neurons via inhibition of MKK4-JNK signaling pathway
AU - Cong, Chao
AU - Kluwe, Lan
AU - Li, Shengnan
AU - Liu, Xiaofei
AU - Liu, Yang
AU - Liu, Huicong
AU - Gui, Wenjia
AU - Liu, Te
AU - Xu, Lianwei
N1 - Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2019/6/12
Y1 - 2019/6/12
N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin (PF) exerts a significant protective effect against neurotoxicity and mitochondrial damage in neurons. However, the mechanisms underlying PF-mediated rescue remain elusive. Therefore, we endeavored to further research the molecular mechanisms underlying PF-mediated inhibition of tributyltin chloride (TBTC)-induced apoptosis of neurons.AIM OF THE STUDY: To investigate the influence and possible mechanism of action of PF in TBTC-induced neurodegenerative disease.MATERIALS AND METHODS: First, primary hypothalamic neurons were treated with tributyltin chloride (150 μg/L) and PF (25, 50, and 100 μM). 17β-estradiol (1 nM) was used as a positive control. Subsequently, CCK-8 assay was performed. The level of apoptosis was examined by flow cytometry and the function of mitochondria was reflected by MMP levels. The mRNA expression levels of B-cell lymphoma-2 (Bcl-2), together with Bax, were examined using qRT-PCR. The protein levels of mitogen-activated protein kinase kinase 4 (MKK4), c-Jun N-terminal kinase (JNK), Bcl-2, Bax, and Caspase-3 were examined using western blotting. Finally, pretreatment with JNK agonist, anisomycin, was done to observe the change in expressions of MKK4 and JNK.RESULTS: Paeoniflorin treatment reduced TBTC-induced damage and neuron loss in a dose-dependent manner. Decrease in mitogen-activated protein kinase (MAPK) as well as JNK levels were reversed by treatment with paeoniflorin via inhibition of JNK activation. Furthermore, ratio of levels of Bcl-2/Bax increased while the activation of caspase-3 was suppressed. In addition, pretreatment with JNK agonist, anisomycin effectively suppressed TBTC-induced cytotoxicity in hypothalamic neuron.CONCLUSIONS: PF can potentially be used to prevent and/or treat neurodegenerative diseases and neural injury by inhibiting MKK4-JNK signaling pathway.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin (PF) exerts a significant protective effect against neurotoxicity and mitochondrial damage in neurons. However, the mechanisms underlying PF-mediated rescue remain elusive. Therefore, we endeavored to further research the molecular mechanisms underlying PF-mediated inhibition of tributyltin chloride (TBTC)-induced apoptosis of neurons.AIM OF THE STUDY: To investigate the influence and possible mechanism of action of PF in TBTC-induced neurodegenerative disease.MATERIALS AND METHODS: First, primary hypothalamic neurons were treated with tributyltin chloride (150 μg/L) and PF (25, 50, and 100 μM). 17β-estradiol (1 nM) was used as a positive control. Subsequently, CCK-8 assay was performed. The level of apoptosis was examined by flow cytometry and the function of mitochondria was reflected by MMP levels. The mRNA expression levels of B-cell lymphoma-2 (Bcl-2), together with Bax, were examined using qRT-PCR. The protein levels of mitogen-activated protein kinase kinase 4 (MKK4), c-Jun N-terminal kinase (JNK), Bcl-2, Bax, and Caspase-3 were examined using western blotting. Finally, pretreatment with JNK agonist, anisomycin, was done to observe the change in expressions of MKK4 and JNK.RESULTS: Paeoniflorin treatment reduced TBTC-induced damage and neuron loss in a dose-dependent manner. Decrease in mitogen-activated protein kinase (MAPK) as well as JNK levels were reversed by treatment with paeoniflorin via inhibition of JNK activation. Furthermore, ratio of levels of Bcl-2/Bax increased while the activation of caspase-3 was suppressed. In addition, pretreatment with JNK agonist, anisomycin effectively suppressed TBTC-induced cytotoxicity in hypothalamic neuron.CONCLUSIONS: PF can potentially be used to prevent and/or treat neurodegenerative diseases and neural injury by inhibiting MKK4-JNK signaling pathway.
KW - Animals
KW - Apoptosis/drug effects
KW - Cells, Cultured
KW - Female
KW - Glucosides/pharmacology
KW - Hypothalamus/cytology
KW - JNK Mitogen-Activated Protein Kinases/metabolism
KW - MAP Kinase Kinase 4/metabolism
KW - Monoterpenes/pharmacology
KW - Neurons/drug effects
KW - Neuroprotective Agents/pharmacology
KW - Rats, Sprague-Dawley
KW - Signal Transduction/drug effects
KW - Trialkyltin Compounds/toxicity
U2 - 10.1016/j.jep.2019.03.030
DO - 10.1016/j.jep.2019.03.030
M3 - SCORING: Journal article
C2 - 30878547
VL - 237
SP - 1
EP - 8
JO - J ETHNOPHARMACOL
JF - J ETHNOPHARMACOL
SN - 0378-8741
ER -
