Diammonium Glycyrrhizinate Attenuates Aβ1–42‐Induced Neuroinflammation and Regulates MAPK and NF‐κB Pathways In Vitro and In Vivo

Zhao, Hui; Wang, Su‐Lei; Lai, Qi; Jin, Jiali; Li, Hui; Xu, Yun; Zhu, Xiaolei

doi:10.1111/cns.12043

Cited by 63 publications

(42 citation statements)

References 25 publications

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“…Among the kinases, MAPKs may be the key participators in the neurodegeneration seen in AD [22,23]. ERK and JNK, which are members of the MAPK superfamily, are closely associated with amyloid deposition and tau phosphorylation in AD and diabetes [24][25][26]. Liraglutide decreases inflammatory stress by inhibiting activation of JNK [27].…”

Section: Discussionmentioning

confidence: 99%

The Neuroprotection of Liraglutide on Alzheimer-Like Learning and Memory Impairment by Modulating the Hyperphosphorylation of Tau and Neurofilament Proteins and Insulin Signaling Pathways in Mice

Xiong

Zheng

Wang

et al. 2013

JAD

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The aim of this study was to investigate the effect of liraglutide on Alzheimer-like learning and memory impairment in mice, which were intracerebroventricularly (i.c.v.) injected with streptozotocin (STZ). Twenty-four mice were randomly divided into three groups: control (CON), AD model (STZ), and liraglutide-treated (LIR). The results show that both hyperphosphorylated tau and neurofilament proteins had deceased protein glycosylation and the tau bound to microtubules was lower in the STZ group compared to the CON group. The expression of JNK phosphorylation was higher and the number of Fluoro-Jade-B-positive degenerative neurons was increased in the STZ group as compared to both the CON and liraglutide groups. Escape latency in the STZ group was longer than that in both the CON and LIR groups, while the number of hidden platform crossings in path length was less than that in the other two groups. Liraglutide decreased the hyperphosphorylation levels of tau and neurofilament proteins, increased protein O-glycosylation, increased tau bound to microtubules, and also significantly improved the learning and memory ability of the mice. These results suggest that the effects of liraglutide on decreasing the hyperphosphorylation of tau and neurofilament proteins by enhancing O-glycosylation of neuronal cytoskeleton protein, improving the JNK and ERK signaling pathway, and reducing neural degeneration may be related to its protective effects on AD-like learning and memory impairment induced by i.c.v. injection of STZ. Our results indicate that GLP-1 analogs represent a novel treatment strategy for Alzheimer's disease.

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Section: Discussionmentioning

confidence: 99%

The Neuroprotection of Liraglutide on Alzheimer-Like Learning and Memory Impairment by Modulating the Hyperphosphorylation of Tau and Neurofilament Proteins and Insulin Signaling Pathways in Mice

Xiong

Zheng

Wang

et al. 2013

JAD

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“…Glycyrrhizic acid (GA), a triterpenoid saponin glycoside from the roots and rhizomes of licorice has been suggested to possess significant anti-inflammatory potential. Diammonium glycyrrhizinate (DG) (Table 1), the salt form of glycyrrhizin acid (GA), has been shown to inhibit Aβ 1–42 induced activation of p65 and MAPK signaling pathways in microglial cells and attenuate memory deficits in Aβ 1-42 induced AD in mice [78]. Xanthoceraside (Table 1), a triterpenoid saponin extracted from the husks of Xanthoceras sorbifolia Bunge has been shown to suppress MAPK and NF-κB signaling and inhibit the release of nitric oxide (NO) and pro-inflammatory cytokines in Aβ peptide induced microglial cells [79].…”

Section: Nf-κb As a Therapeutic Target For Neurodegenerative Diseasesmentioning

confidence: 99%

Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer’s disease and multiple sclerosis

Srinivasan

Lahiri

2015

Expert Opinion on Therapeutic Targets

142

116

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INTRODUCTION Advances in molecular pathogenesis suggest that the chronic inflammation is a shared mechanism in the initiation and progression of multiple neurodegenerative diseases with diverse clinical manifestations such as Alzheimer’s disease (AD) and multiple sclerosis (MS). Restricted cell renewal and regenerative capacity makes the neural tissues extremely vulnerable to the uncontrolled inflammatory process leading to irreversible tissue damage. AREAS COVERED A predominant consequence of increased inflammatory signaling is the upregulation of the transcription factor, nuclear factor-kappa B (NF–κB) with subsequent neuroprotective or deleterious effects depending on the strength of the signal and the type of NF–κB dimers activated. We discuss the interplay between neuroinflammation and neurodegeneration keeping in focus NF-κB signaling as the point of convergence of multiple pathways associated with the development of the neurodegenerative pathologies, AD and MS. EXPERT OPINION Considerable interest exists in developing efficient NF-κB inhibitors for neurodegenerative diseases. The review includes an overview of natural compounds and rationally designed agents that inhibit NF–κB and mediate neuroprotection in AD and MS. The key chemical moieties of the natural and the synthetic compounds provide efficient leads for the development of effective small molecule inhibitors that selectively target NF–κB activation; this would result in the desired benefit to risk therapeutic effects.

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“…LPS binds mostly to toll-like receptor 4 (TLR4), a transmembrane receptor, consequently inducing intracellular signaling, which results in the activation of MAPKs and NF-jB signaling (Rousseau et al 2013). Interestingly, MAPKs including JNK, p38 and ERK1/2 have been described as the key regulators of proinflammatory cytokine production during inflammation induced by LPS (Zhao et al 2013). Recently it has been shown that microglia activation can also be governed by mechanisms involving caspase signaling.…”

Section: R E T R a C T E Dmentioning

confidence: 99%

Retracted: Anti‐inflammatory properties of tianeptine on lipopolysaccharide‐induced changes in microglial cells involve toll‐like receptor‐related pathways

Ślusarczyk

Trojan

Głombik

et al. 2016

Journal of Neurochemistry

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Accumulating evidence suggests that activation of microglia plays a key role in the pathogenesis of depression. Activated microglia produce a wide range of factors whose prolonged or excessive release may lead to brain disorders. Thus, the inhibition of microglial cells may be beneficial in the treatment of depressive diseases. Tianeptine is an atypical antidepressant drug with proven clinical efficacy, but its mechanism of action remains still not fully understood. In the present study, using microglial cultures we investigated whether tianeptine modifies microglial activation after lipopolysaccharide (LPS) stimulation and which intracellular pathways are involved in the activity of this antidepressant. Our study shows that tianeptine attenuated the LPS-evoked inflammatory activation of microglia by decreasing the expression of proinflammatory cytokines such as IL-1b, IL-18, IL-6 and tumor necrosis factor a (TNF-a), the release of nitric oxide (NO) and reactive oxygen species (ROS) as well as the expression of inducible nitric oxide synthase. Analyses of signaling pathways demonstrate that tianeptine led to the suppression of LPS-induced TLR4 expression and ERK1/2 phosphorylation. Furthermore, our study reveals the inhibitory impact of tianeptine on caspase-3-induced PKCd degradation and consequently on the activation of NF-jB factor in microglial cells. Taken together, present results show anti-inflammatory properties of tianeptine in microglial cultures stimulated by LPS. This study provides evidence that the inhibition of microglial activation may underlie the therapeutic activity of tianeptine. Keywords: antidepressant drugs, cytokines, inflammation, intracellular pathways, microglia, tianeptine. J. Neurochem. (2016) 136, 958-970. Increasing evidence indicates that microglia, the resident immune cells in the central nervous system (CNS), may be considered the main mediators of inflammation-associated disorders. These cells manage the innate and adaptive immune responses in various pathological processes including brain trauma, ischemia, stroke and infections, as well as during CNS repair (Graeber and Streit 2010;Yang et al. 2011). It has been observed that active microglia can clear Received September 29, 2015; revised manuscript received November 16, 2015; accepted November 17, 2015. Address correspondence and reprint requests to Agnieszka BastaKaim, Department of Experimental Neuroendocrinology, Polish Academy of Sciences, 12 Sme z tna St., 31-343 Krak ow, Poland. E-mail: basta@if-pan.krakow.plAbbreviations used: AP-1, activator protein-1; CD40, cluster of differentiation 40; DCFH, 2 0 ,7 0 -dichlorodihydrofluorescin; DCFH-DA, 2 0 ,7 0 -dichlorofluorescin diacetate; DMEM, Dulbecco's modified Eagle medium; FAM, fluorescein amidite; FBS, fetal bovine serum; HBSS, Hank's Balanced Salt Solution; HPA, hypothalamus-pituitary-adrenal; IL-18, interleukin 18; IL-1b, interleukin 1b; IL-6, interleukin 6; JNK, cJun N-terminal kinase; LDH, lactate dehydrogenase; MCP-1, monocyte chemoattractant protein-1;...

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Diammonium Glycyrrhizinate Attenuates Aβ_1–42‐Induced Neuroinflammation and Regulates MAPK and NF‐κB Pathways In Vitro and In Vivo

Abstract: DG protects Aβ(1-42) -induced AD models in vitro and in vivo through reducing activation of microglia and inflammation, which may be involved in MAPK and NF-κB pathways.

Cited by 63 publications

References 25 publications

The Neuroprotection of Liraglutide on Alzheimer-Like Learning and Memory Impairment by Modulating the Hyperphosphorylation of Tau and Neurofilament Proteins and Insulin Signaling Pathways in Mice

The Neuroprotection of Liraglutide on Alzheimer-Like Learning and Memory Impairment by Modulating the Hyperphosphorylation of Tau and Neurofilament Proteins and Insulin Signaling Pathways in Mice

Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer’s disease and multiple sclerosis

Retracted: Anti‐inflammatory properties of tianeptine on lipopolysaccharide‐induced changes in microglial cells involve toll‐like receptor‐related pathways

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