Isoliquiritigenin Isolated from Licorice<i>Glycyrrhiza uralensis</i>Prevents 6-Hydroxydopamine-Induced Apoptosis in Dopaminergic Neurons

Hwang, Cheol Kyu; Chun, Hong Sung

doi:10.1271/bbb.110842

Cited by 81 publications

(37 citation statements)

References 40 publications

(57 reference statements)

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“…Results from our study have powerful evidence showing that ILG possesses a brain cell-protective function, and this was in line with previous studies in vivo [47–50] and in vitro [26, 51, 52]. Pretreatment of ILG significantly alleviated neurological deficits, cerebral infarct, and brain edema, and these neuroprotective effects are involved in the increases of brain ATP content, energy charge (EC) and total adenine nucleotides (TAN) and preservation of brain Na + K + ATPase activity, SOD, CAT, and GSH-Px, and inhibition of the increase of brain MDA content in a rat cerebral ischemia-reperfusion model [50].…”

Section: Discussionsupporting

confidence: 92%

“…Toxicity of brain cells induced by cocaine and methamphetamine delivery was also able to be attenuated by ILG treatment [47–49]. Consistently, in in vitro studies, ILG protected neuronal cells from glutamate and 6-hydroxydopamine (6-OHDA)-induced neurotoxicity by reducing the production of ROS [51, 52]. Meanwhile, a recent report also showed that ILG treatment could notably alleviate rotenone and sodium nitroprusside (SNP)-induced oxidative stress and nitrosative stress by improving MMP, ATP levels, and neural cell viability [26].…”

Section: Discussionmentioning

confidence: 82%

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Isoliquiritigenin alleviates early brain injury after experimental intracerebral hemorrhage via suppressing ROS- and/or NF-κB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway

Zeng

Chen

Ding

et al. 2017

J Neuroinflammation

292

214

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BackgroundIntracerebral hemorrhage (ICH) induces potently oxidative stress responses and inflammatory processes. Isoliquiritigenin (ILG) is a flavonoid with a chalcone structure and can activate nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant system, negatively regulate nuclear factor-κB (NF-κB) and nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathways, but its role and potential molecular mechanisms in the pathology following ICH remain unclear. The present study aimed to explore the effects of ILG after ICH and underlying mechanisms.MethodsICH model was induced by collagenase IV (0.2 U in 1 μl sterile normal saline) in male Sprague-Dawley rats weighing 280–320 g. Different doses of ILG (10, 20, or 40 mg/kg) was administrated intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling, respectively. Rats were intracerebroventricularly administrated with control scramble small interfering RNA (siRNA) or Nrf2 siRNA at 24 h before ICH induction, and after 24 h, ICH model was established with or without ILG (20 mg/kg) treatment. All rats were dedicated at 24 or 72 h after ICH. Neurological deficits, histological damages, brain water content (BWC), blood-brain barrier (BBB) disruption, and neuronal degeneration were evaluated; quantitative real-time RT-PCR (qRT-PCR), immunohistochemistry/immunofluorescence, western blot, and enzyme-linked immunosorbent assay (ELISA) were carried out; catalase, superoxide dismutase activities and reactive oxygen species (ROS), and glutathione/oxidized glutathione contents were measured.ResultsILG (20 and 40 mg/kg) markedly alleviated neurological deficits, histological damages, BBB disruption, brain edema, and neuronal degeneration, but there was no significant difference between two dosages. ILG (20 mg/kg) significantly suppressed the NF-κB and NLRP3 inflammasome pathways and activated Nrf2-mediated antioxidant system. Gene silencing of Nrf2 aggravated the neurological deficits, brain edema, and neuronal degeneration and increased the protein levels of NF-κB p65, NLRP3 inflammasome components, and IL-1β. ILG delivery significantly attenuated the effects of Nrf2 siRNA interference mentioned above.ConclusionsIntraperitoneal administration of ILG after ICH reduced early brain impairments and neurological deficits, and the mechanisms were involved in the regulation of ROS and/or NF-κB on the activation of NLRP3 inflammasome pathway by the triggering of Nrf2 activity and Nrf2-induced antioxidant system. In addition, our experimental results may make ILG a potential candidate for a novel therapeutical strategy for ICH.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0895-5) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 82%

Isoliquiritigenin alleviates early brain injury after experimental intracerebral hemorrhage via suppressing ROS- and/or NF-κB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway

Zeng

Chen

Ding

et al. 2017

J Neuroinflammation

292

214

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“…4a and 4c). In consideration of ROS elevation believed to initiate a neurotoxic cascade induced by 6-OHDA [20], we further examined if Wnt3a-CM inhibit 6-OHDA-induced cell apoptosis by suppressing ROS production. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Wnt3a protects SH-SY5Y cells against 6-hydroxydopamine toxicity by restoration of mitochondria function

Wei

et al. 2015

Transl Neurodegener

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BackgroundWnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases, including Parkinson’s disease (PD). This study aimed to investigate the neuroprotective effects of actived Wnt/β-catenin signal by Wnt3a on SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA).MethodsWnt3a-conditioned medium (Wnt3a-CM) was used to intervene dopaminegic SH-SY5Y cells treated with 6-OHDA. Cell toxicity was determined by cell viability and lactate dehydrogenase leakage (LDH) assay. The mitochondria function was measured by the mitochondrial membrane potential, while oxidative stress was monitored with intracellular reactive oxygen species (ROS). Western blot analysis was used to detect the expression of GSK3β, β-catenin as well as Akt.ResultsOur results showed that 100 μM 6-OHDA treated for 24 h significantly decreased cell viability and mitochondrial transmembrane potential, reduced the level of β-catenin and p-Akt, increased LDH leakage, ROS production and the ratio of p-GSK3β (Tyr216) to p-GSK3β (Ser9). However, Wnt3a-conditioned medium reversing SH-SY5Y cells against 6-OHDA-induced neurotoxicity by reversing these changes.ConclusionsActivating of Wnt/β-catenin pathway by Wnt3a-CM attenuated 6-OHDA-induced neurotoxicity significantly, which related to the inhibition of oxidative stress and maintenance of normal mitochondrial function.

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“…Previous studies showed that 6-OHDA induces apoptosis [15], [16], as evidenced by the presence of apoptotic bodies. Here, we found that nuclear fragmentation induced by 6-OHDA treatment was dramatically reduced when the cells were pre-treated with phloroglucinol for 1 h, prior to 6-OHDA treatment, with a significant reduction in the apoptotic index from 7.5 to 3 (* p <0.05, Figure 3C).…”

Section: Resultsmentioning

confidence: 99%

Phloroglucinol Attenuates Motor Functional Deficits in an Animal Model of Parkinson's Disease by Enhancing Nrf2 Activity

et al. 2013

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In this study, we investigated whether phloroglucinol (1, 3, 5 - trihydroxybenzene) has therapeutic effects in cellular and animal model of Parkinson's disease (PD). PD is the second most common, chronic and progressive neurodegenerative disease, and is clinically characterized with motor dysfunctions such as bradykinesia, rigidity, postural instability, gait impairment, and resting tremor. In the brains of PD patients, dopaminergic neuronal loss is observed in the Substantia nigra. Although the exact mechanisms underlying PD are largely unknown, mitochondrial dysfunction and oxidative stress are thought to be critical factors that induce the onset of the disease. Here, phloroglucinol administration was shown to attenuate motor functional deficits evaluated with rota-rod and apomorphine-induced rotation tests in 6-hydroxydopamine (6-OHDA)-induced PD animal models. Moreover, phloroglucinol ameliorated the loss of synapses as assessed with protein levels and immunoreactivity against synaptophysin in the midbrain region of the 6-OHDA-lesioned rats. In addition, in SH-SY5Y cultures, the cytotoxicity of 6-OHDA was reduced by pre-treatment with phloroglucinol. The increase in the reactive oxygen species, lipid peroxidation, protein carbonyl formation and 8-hydroxyguanine caused by treatment with 6-OHDA was attenuated by phloroglucinol in SH-SY5Y cells. Furthermore, phloroglucinol treatment rescued the reduced levels of nuclear Nrf2, antioxidant enzymes, i.e., catalase and glutathione peroxidase, in 6-OHDA-treated cells. Taken together, phloroglucinol has a therapeutic potential for treatment of PD.

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Isoliquiritigenin Isolated from LicoriceGlycyrrhiza uralensisPrevents 6-Hydroxydopamine-Induced Apoptosis in Dopaminergic Neurons

Cited by 81 publications

References 40 publications

Isoliquiritigenin alleviates early brain injury after experimental intracerebral hemorrhage via suppressing ROS- and/or NF-κB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway

Isoliquiritigenin alleviates early brain injury after experimental intracerebral hemorrhage via suppressing ROS- and/or NF-κB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway

Wnt3a protects SH-SY5Y cells against 6-hydroxydopamine toxicity by restoration of mitochondria function

Phloroglucinol Attenuates Motor Functional Deficits in an Animal Model of Parkinson's Disease by Enhancing Nrf2 Activity

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