PI3K/AKT signaling mediated by G protein-coupled receptors is involved in neurodegenerative Parkinson's disease (Review)

Nakano, Nobuhiko; Matsuda, Satoru; Ichimura, Mayuko; Minami, Akari; Ogino, Mako; Murai, Toshiyuki; Kitagishi, Yasuko

doi:10.3892/ijmm.2016.2833

Cited by 82 publications

(49 citation statements)

References 86 publications

(84 reference statements)

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“…In addition, some authors suggest that honokiol can inhibit nuclear factor kappa light chain enhancer of activated B cells activation in mouse B cells [31], macrophages [4] and lipopolysaccharide-induced microglia cells [52]. It is also believed that honokiol can selectively modulate the phosphoinositide 3-kinase/Akt pathway [18,35,53].…”

Section: Discussionmentioning

confidence: 99%

Expression of vascular endothelial growth factor and glial fibrillary acidic protein in a rat model of traumatic brain injury treated with honokiol: a biochemical and immunohistochemical study

Çetin

Deveci

2019

Folia Morphol

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Background: Traumatic brain injury (TBI) leads to neuronal damage and neurological dysfunction. The aim of our study was to investigate the antioxidative effect of honokiol on TBI in rats with biochemical, histopathological and immunohistochemical methods. Materials and methods: Sprague-Dawley rats were subjected to TBI with a weight-drop device using 300 g/1 m weight/height impact. Forty-five rats were divided into three groups as control group, TBI group and TBI + honokiol group (5 mg/kg/day, i.p.). Honokiol (5 mg/kg) dissolved in dimethyl sulfoxide (DMSO) was intraperitoneally administered to rats for 7 days after the trauma. At the end of experiment, blood samples were taken from the animals and analysed with various biochemical markers. Results: Histopathological examination of the trauma group revealed some degenerated pyramidal cells, dilatation and congestion in blood vessels, hyperplasia in endothelial cells, inflammatory cell infiltration around the vein and disruptions in glial extensions. In TBI + honokiol group, pyramidal neurons showed a decrease in degeneration, slight dilatation in blood vessels, improvement of endothelial cells towards the lumen, and reduction of inflammatory cells in the vessel. In TBI + honokiol group, vascular endothelial growth factor expression was positive in the endothelial and few inflammatory cells of the mildly dilated blood vessels. In the blood brain barrier deteriorated after trauma, it was observed that the glial foot processes were positive expression and extended to the endothelial cells in the TBI + honokiol group. Conclusions: Glial fibrillary acidic protein expression showed a positive reaction in these processes. Considering the important role of antioxidants and inflammatory responses in cerebral damage induced by traumatic head injury, honokiol is thought to be important in decreasing lipid peroxidation, protecting the membrane structure of blood brain barrier, degeneration of neurons and glial cells. (Folia Morphol 2019; 78, 4: 684-694)

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Section: Discussionmentioning

confidence: 99%

Expression of vascular endothelial growth factor and glial fibrillary acidic protein in a rat model of traumatic brain injury treated with honokiol: a biochemical and immunohistochemical study

Çetin

Deveci

2019

Folia Morphol

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“…Furthermore, data suggest that honokiol can inhibit NF‐κB activation in mouse B cells , macrophages and in LPS‐stimulated microglia cells . It is also thought that honokiol may selectively modulate the PI3K/Akt pathway . Treatment with honokiol lowered TNF‐α‐induced phosphorylation of the kinases: p38, ERK1/2 and JNKs .…”

Section: Honokiol and Neuroinflammationmentioning

confidence: 99%

Neuroprotective effects of honokiol: from chemistry to medicine

et al. 2017

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The incidence of neurological disorders is growing in developed countries together with increased lifespan. Nowadays, there are still no effective treatments for neurodegenerative pathologies, which make necessary to search for new therapeutic agents. Natural products, most of them used in traditional medicine, are considered promising alternatives for the treatment of neurodegenerative diseases. Honokiol is a natural bioactive phenylpropanoid compound, belonging to the class of neolignan, found in notable amounts in the bark of Magnolia tree, and has been reported to exert diverse pharmacological properties including neuroprotective activities. Honokiol can permeate the blood brain barrier and the blood-cerebrospinal fluid to increase its bioavailability in neurological tissues. Diverse studies have provided evidence on the neuroprotective effect of honokiol in the central nervous system, due to its potent antioxidant activity, and amelioration of the excitotoxicity mainly related to the blockade of glutamate receptors and reduction in neuroinflammation. In addition, recent studies suggest that honokiol can attenuate neurotoxicity exerted by abnormally aggregated Aβ in Alzheimer's disease. The present work summarizes what is currently known concerning the neuroprotective effects of honokiol and its potential molecular mechanisms of action, which make it considered as a promising agent in the treatment and management of neurodegenerative diseases. © 2017 BioFactors, 43(6):760-769, 2017.

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“…Activation of MAPK and Akt signaling pathways leads to the expression of inflammatory factors and promotes inflammatory processes by promoting oxidative stress responses. Therefore, Akt and MAPK signaling pathways are considered to be crucial mechanisms in controlling inflammatory activity by producing inflammatory mediators . As shown in Figure , to assess whether AS‐6 affected MAPK and Akt phosphorylation of LPS‐activated BV2 cells, the cells were pretreated with AS‐6 in advance LPS activation and phosphorylation of p38, ERK, JNK, and Akt oxidation was assayed.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, Akt and MAPK signaling pathways are considered to be crucial mechanisms in controlling inflammatory activity by producing inflammatory mediators. [22][23][24][25] As shown in Figure 5, to assess whether AS-6 affected MAPK and Akt phosphorylation of LPS-activated BV2 cells, the cells were pretreated with AS-6 in advance LPS activation and phosphorylation of p38, ERK, JNK, and Akt oxidation was assayed. AS-6 reduced p-ERK, p-JNK, p-p38, and p-Akt expression in LPS-stimulated BV2 cells.…”

Section: As-6 Suppresses Erk P38 Jnk and Akt Phosphorylation Inmentioning

confidence: 99%

4‐O‐carboxymethylascochlorin protected against microglial‐mediated neurotoxicity in SH‐SY5Y and BV2 cocultured cells from LPS–induced neuroinflammation and death by inhibiting MAPK, NF‐κB, and Akt pathways

Park

Abekura

et al. 2018

J of Cellular Biochemistry

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In our previous studies, structurally similar compounds of ascochlorin and ascofuranone exhibited anti‐inflammatory activity. Neural inflammation plays a significant role in the commence and advancement of neurodegenerative diseases. It is not known whether 4‐O‐carboxymethylascochlorin (AS‐6) regulates the initial stage of inflammatory responses at the cellular level in BV2 microglia cells. We here investigated the anti‐inflammatory effects of AS‐6 treatment in microglia cells with the microglial protection in neurons. We found that the lipopolysaccharide (LPS)‐stimulated production of nitric oxide, a main regulator of inflammation, is suppressed by AS‐6 in BV2 microglial cells. In addition, AS‐6 dose‐dependently suppressed the increase in COX‐2 protein and messenger RNA levels in LPS‐stimulated BV2 cells. Moreover, AS‐6 inhibited the expression and secretion of proinflammatory cytokines in BV2 microglial cells. At the intracellular level, AS‐6 inhibited LPS‐activated nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) in BV2 microglial cells. AS‐6 negatively affected mitogen‐activated protein kinases (MAPK) and Akt phosphorylation: Phosphorylated forms of ERK, JNK, p38, and Akt decreased. To check whether AS‐6 protects against inflammatory inducer‐mediated neurotoxicity, neuronal SH‐SY5Y cells were coincubated with BV2 cells in conditioned medium. AS‐6 exerted a neuroprotective effect by suppressing microglial activation by LPS or amyloid‐β peptide. AS‐6 is a promising suppressor of inflammatory responses in LPS‐induced BV2 cells by attenuating NF‐κB and MAPKs signaling. AS‐6 protected against microglial‐mediated neurotoxicity in SH‐SY5Y and BV2 cocultured cells from LPS–induced neuroinflammation and death via inhibiting MAPK, NF‐κB, and Akt pathways.

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PI3K/AKT signaling mediated by G protein-coupled receptors is involved in neurodegenerative Parkinson's disease (Review)

Cited by 82 publications

References 86 publications

Expression of vascular endothelial growth factor and glial fibrillary acidic protein in a rat model of traumatic brain injury treated with honokiol: a biochemical and immunohistochemical study

Expression of vascular endothelial growth factor and glial fibrillary acidic protein in a rat model of traumatic brain injury treated with honokiol: a biochemical and immunohistochemical study

Neuroprotective effects of honokiol: from chemistry to medicine

4‐O‐carboxymethylascochlorin protected against microglial‐mediated neurotoxicity in SH‐SY5Y and BV2 cocultured cells from LPS–induced neuroinflammation and death by inhibiting MAPK, NF‐κB, and Akt pathways

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