Inhibition of nuclear factor κB is associated with neuroprotective effects of glycyrrhizic acid on glutamate-induced excitotoxicity in primary neurons

Cherng, Jaw-Ming; Lin, Hsiang‐Ju; Hung, Man-Shan; Lin, Yu; Chan, Ming‐Huan; Lin, Jung‐Chung

doi:10.1016/j.ejphar.2006.06.080

Cited by 80 publications

(57 citation statements)

References 41 publications

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“…A more recent study indicated that GA supplementation suppressed the development of 1,2-dimethyhydrazine (DMH)-induced precancerous lesions in Wistar rat colon. It also reduced the infiltration of mast cells, attenuated the expression of Ki-67, NF-κB/ p65, COX-2, inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF), while enhancing the expression of p53, connexin-43, caspase-9, and cleaved caspase-3, which suggested the induction of apoptosis [43], also agreeing with other studies [29,42]. GA reportedly induced G0/G1 phase arrest, apoptosis, and DNA damage in WEHI-3 leukemia cells by increasing reactive oxygen species (ROS) levels and caspase-3 activity in these cells [44].…”

Section: Glycyrrhizin and Glycyrrhetic Acidsupporting

confidence: 79%

“…These investigators also observed inhibition of NF-κB and cyclooxygenase-2 (COX-2) activities and decreased prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) levels, which appears to be a common observation. The evidence suggested that the anticancer effects of GA were mediated through the blockade of NF-κB activation by interfering with the phosphorylation or degradation of IκB [29]. A more recent study indicated that GA supplementation suppressed the development of 1,2-dimethyhydrazine (DMH)-induced precancerous lesions in Wistar rat colon.…”

Section: Glycyrrhizin and Glycyrrhetic Acidmentioning

confidence: 99%

“…It was reported to exert protection against carbon tetrachloride-induced liver injury in mice [25], liver damage associated with aflatoxin-induced oxidative stress [26] and other types of liver damage induced by oxidative stress [27]. These licorice compounds also can induce interferon production [26,28] and protect against neurotoxicity by modulating the binding of nuclear factorkappaB to its molecular targets [29].…”

Section: Glycyrrhizin and Glycyrrhetic Acidmentioning

confidence: 99%

“…The effects of GA were examined in an UVBirradiation-induced skin tumor study and results indicated that feeding mice GA before UVB irradiation (180 mJ/cm 2 twice per week) resulted in delayed tumor appearance and decreased multiplicity and size [29]. Mice fed GA for 2 weeks before a single UVB exposure (180 mJ/cm 2 ) exhibited decreased UVB-induced thymine dimer-positive cells, reduced expression of proliferative cell nuclear antigen (PCNA), and exhibited fewer TUNEL (terminal deoxynucleotidyl transferasemediated dUTP nick end labeling)-positive cells.…”

Section: Glycyrrhizin and Glycyrrhetic Acidmentioning

confidence: 99%

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Chemopreventive Effects of Licorice and Its Components

Bode

Dong

2015

Curr Pharmacol Rep

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Section: Glycyrrhizin and Glycyrrhetic Acidsupporting

confidence: 79%

Section: Glycyrrhizin and Glycyrrhetic Acidmentioning

confidence: 99%

Section: Glycyrrhizin and Glycyrrhetic Acidmentioning

confidence: 99%

Section: Glycyrrhizin and Glycyrrhetic Acidmentioning

confidence: 99%

See 2 more Smart Citations

Chemopreventive Effects of Licorice and Its Components

Bode

Dong

2015

Curr Pharmacol Rep

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“…GA, one of the triterpenoid saponin glycoside, was found to protect PC12 cells from 1-methyl-4-phenylpyridinium-induced cytotoxicity (11). GA alters inflammatory processes by modulating NF-κB activities (12) and by blocking the activation of NF-κB in primary neurons (13). Furthermore, it was reported that the neuroprotective effects of GA in PC12 cells is via modulation of the PI3K/Akt pathway (14).…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizic acid induces apoptosis in WEHI-3 mouse leukemia cells through the caspase- and mitochondria-dependent pathways

et al. 2012

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Abstract. Leukemia, one of the causes of cancer-related death in humans, is an aggressive malignancy via the rapid growth of abnormal white blood cells. The aim of this study was to determine the anti-leukemia effect of glycyrrhizic acid (GA) on a mouse leukemia cell line, WEHI-3. GA, an active compound in Glycyrrhiza glabra, has been proven to induce cytotoxic effects in many cancer cell lines. In the current study, we investigated the effects of GA in mouse leukemia cells in vitro. The results indicated that GA induced morphological changes, G 0 /G 1 phase arrest, apoptosis and DNA damage in WEHI-3 cells as determined by phase contrast microscopy, DAPI-staining, flow cytometry and comet assay. The results from the flow cytometric assay showed that GA increased ROS levels, reduced the mitochondrial membrane potential (ΔΨm) and stimulated caspase-3 activity in WEHI-3 cells. GA regulated the intrinsic and extrinsic apoptosis-associated protein expression which was determined by western blotting. In addition, endoplasmic reticulum (ER) stress responses were observed in GA-treated WEHI-3 cells. GA promoted the trafficking of apoptosis-inducing factor (AIF), cytochrome c and endonuclease G (Endo G) in WEHI-3 cells. Based on this evidence, GA-triggered apoptosis occurs through the death receptor, mitochondria-mediated and ER stress multiple signaling pathways.

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Inhibition of Connexin 36 attenuates HMGB1‐mediated depressive‐like behaviors induced by chronic unpredictable mild stress

Jiang

Zeng

et al. 2022

Brain and Behavior

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Background: High mobility group box 1 (HMGB1) released by neurons and microglia was demonstrated to be an important mediator in depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which could lead to the imbalance of two different metabolic approaches in kynurenine pathway (KP), thus enhancing glutamate transmission and exacerbating depressive-like behaviors. Evidence showed that HMGB1 signaling might be regulated by Connexin (Cx) 36 in inflammatory diseases of central nervous system (CNS). Our study aimed to further explore the role of Cx36 in depressive-like behaviors and its relationship with HMGB1.Methods: After 4-week chronic stress, behavioral tests were conducted to evaluate depressive-like behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Western blot analysis and immunofluorescence staining were used to observe the expression and location of Cx36. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the concentrations of inflammatory cytokines. And the excitability and inward currents of hippocampal neurons were recorded by whole-cell patch clamping. Results:The expression of Cx36 was significantly increased in hippocampal neurons of mice exposed to CUMS, while treatment with glycyrrhizinic acid (GZA) or quinine could both down-regulate Cx36 and alleviate depressive-like behaviors. The proinflammatory cytokines like HMGB1, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were all elevated by CUMS, and application of GZA and quinine could decrease them. In addition, the enhanced excitability and inward currents of hippocampal neurons induced by lipopolysaccharide (LPS) could be reduced by either GZA or quinine.Conclusions: Inhibition of Cx36 in hippocampal neurons might attenuates HMGB1mediated depressive-like behaviors induced by CUMS through down-regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload.

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Inhibition of nuclear factor κB is associated with neuroprotective effects of glycyrrhizic acid on glutamate-induced excitotoxicity in primary neurons

Cited by 80 publications

References 41 publications

Chemopreventive Effects of Licorice and Its Components

Chemopreventive Effects of Licorice and Its Components

Glycyrrhizic acid induces apoptosis in WEHI-3 mouse leukemia cells through the caspase- and mitochondria-dependent pathways

Inhibition of Connexin 36 attenuates HMGB1‐mediated depressive‐like behaviors induced by chronic unpredictable mild stress

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