Neuroprotective effect of Chunghyuldan from amyloid beta oligomer induced neuroinflammation in vitro and in vivo

2014 ◽  
Vol 92 (6) ◽  
pp. 429-437 ◽  
Author(s):  
Hyo Geun Kim ◽  
Ji-Young Kim ◽  
Wei-Wan Whang ◽  
Myung Sook Oh
Keyword(s):  
Cognitive Impairment ◽  
Amyloid Beta ◽  
Antioxidant Activities ◽  
Neuronal Damage ◽  
Biological Effects ◽  
Neuroprotective Effect ◽  
In Vivo Models ◽  
Aβ Oligomer

Microglia-mediated inflammation is a major pathological mechanism contributing to Alzheimer’s disease (AD), and has been proposed as a potential therapeutic target. Chunghyuldan (CHD; Qingxue-dan in Chinese and Daio-Orengedokuto in Japanese) possesses wide-ranging biological effects, including anti-hyperlipidemic, anti-stroke, anti-inflammatory, and antioxidant activities that could affect neurological functions. In this study, we examined the effects of CHD in in-vitro and in-vivo models of AD induced by the oligomeric form of amyloid-beta (Aβ oligomer), which acts directly on microglia-mediated neuroinflammation to result in neuronal damage and cognitive impairment. CHD at 0.1–100 μg·mL−1 significantly protected PC12 cells and rat primary hippocampal cells from Aβ oligomer1–42 toxicity. In addition, CHD at 1–10 μg·mL−1 inhibited Aβ oligomer1–42 induced production of nitric oxide, tumor necrosis factor-α, and interleukin-1β in microglial cells. In an in-vivo AD model, administration of CHD (50 mg·(kg body mass)−1, for 5 days, per oral) inhibited the activation of astrocytes and microglia in the dentate gyrus and neuronal damage in the CA1 of the ipsilateral hippocampus. Moreover, CHD ameliorated cognitive impairment induced by Aβ oligomer1–42 toxicity. These results demonstrate the neuroprotective effects of CHD through inhibition of microglia-mediated neuroinflammation in in-vitro and in-vivo AD-like models induced by Aβ oligomer1–42 toxicity.

scholarly journals DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Tao Tao ◽  
Guang-Jie Liu ◽  
Xuan Shi ◽  
Yan Zhou ◽  
Yue Lu ◽  
...  
Keyword(s):  
Subarachnoid Haemorrhage ◽  
Microglial Activation ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Early Brain Injury ◽  
Protective Effects ◽  
In Vivo Models ◽  
The Brain

Abstract Background Microglia are resident immune cells in the central nervous system and central to the innate immune system. Excessive activation of microglia after subarachnoid haemorrhage (SAH) contributes greatly to early brain injury, which is responsible for poor outcomes. Dehydroepiandrosterone (DHEA), a steroid hormone enriched in the brain, has recently been found to regulate microglial activation. The purpose of this study was to address the role of DHEA in SAH. Methods We used in vivo models of endovascular perforation and in vitro models of haemoglobin exposure to illustrate the effects of DHEA on microglia in SAH. Results In experimental SAH mice, exogenous DHEA administration increased DHEA levels in the brain and modulated microglial activation. Ameliorated neuronal damage and improved neurological outcomes were also observed in the SAH mice pretreated with DHEA, suggesting neuronal protective effects of DHEA. In cultured microglia, DHEA elevated the mRNA and protein levels of Jumonji d3 (JMJD3, histone 3 demethylase) after haemoglobin exposure, downregulated the H3K27me3 level, and inhibited the transcription of proinflammatory genes. The devastating proinflammatory microglia-mediated effects on primary neurons were also attenuated by DHEA; however, specific inhibition of JMJD3 abolished the protective effects of DHEA. We next verified that DHEA-induced JMJD3 expression, at least in part, through the tropomyosin-related kinase A (TrkA)/Akt signalling pathway. Conclusions DHEA has a neuroprotective effect after SAH. Moreover, DHEA increases microglial JMJD3 expression to regulate proinflammatory/anti-inflammatory microglial activation after haemoglobin exposure, thereby suppressing inflammation.

scholarly journals Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 595 ◽  
Author(s):  
Irwin K. Cheah ◽  
Barry Halliwell
Keyword(s):  
Distress Syndrome ◽  
Neuronal Damage ◽  
Multiorgan Failure ◽  
The Elderly ◽  
Ischemia And Reperfusion Injury ◽  
In Vivo Models ◽  
Dietary Amino Acid ◽  
Underlying Pathology

Infection with SARS-CoV-2 causes the coronavirus infectious disease 2019 (COVID-19), a pandemic that has, at present, infected more than 11 million people globally. Some COVID-19 patients develop a severe and critical illness, spurred on by excessive inflammation that can lead to respiratory or multiorgan failure. Numerous studies have established the unique array of cytoprotective properties of the dietary amino acid ergothioneine. Based on studies in a range of in vitro and in vivo models, ergothioneine has exhibited the ability to modulate inflammation, scavenge free radicals, protect against acute respiratory distress syndrome, prevent endothelial dysfunction, protect against ischemia and reperfusion injury, protect against neuronal damage, counteract iron dysregulation, hinder lung and liver fibrosis, and mitigate damage to the lungs, kidneys, liver, gastrointestinal tract, and testis, amongst many others. When compiled, this evidence suggests that ergothioneine has a potential application in the treatment of the underlying pathology of COVID-19. We propose that ergothioneine could be used as a therapeutic to reduce the severity and mortality of COVID-19, especially in the elderly and those with underlying health conditions. This review presents evidence to support that proposal.

scholarly journals Neuroprotective effect of thiamine triethylorthoformate conjugate against Parkinson disease in a mouse model

2021 ◽  
Vol 18 (5) ◽  
pp. 1041-1047
Author(s):  
Yan Dong ◽  
Qing Xu ◽  
Xi Jia ◽  
Chao Li ◽  
Dan Xu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Parkinson Disease ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Down Regulation ◽  
Pre Treatment ◽  
Jnk Activation

Purpose: To investigate the effect of thiamine triethylorthoformate conjugate (TTO) on Parkinson disease (PD) in vitro and in vivo in a mice model. Methods: The effect of TTO on behavioural changes in PD mouse model was studied using pole, traction and swimming tests. Astrocyte proliferation after TTO treatment was assessed using 3 (4, 5 dimethyl 2 thi¬azolyl) 2, 5 diphenyl 2 H tetrazolium bromide (MTT) assay. Apoptosis was determined with flow cytometry using Annexin V Fluorescein isothiocyanate kit. Results: Treatment of PD mice with TTO led to a decrease in climbing time, increase in suspension score and enhancement of swimming score, when compared to the untreated group (p < 0.05). Treatment of astrocytes with TTO prior to MPP incubation significantly increased proliferation (p < 0.05). Apoptosis induction in astrocytes by MPP was attenuated by pre-treatment with TTO. Pre-treatment of astrocytes with 10 µM TTO markedly reduced JNK activation, when compared to astrocytes incubated with MPP alone (p < 0.05). Up-regulation of Bax and down-regulation of Bcl 2 by MPP in astrocytes were attenuated by pre-treatment with TTO. MPP-induced up-regulation of cleaved caspase 3 was suppressed in astrocytes by TTO pre-treatment (p < 0.05). Conclusion: Treatment with TTO prevents MPP+ -induced neuronal damage in vitro in astrocytes and in vivo in mice. The neuro-protective effect of TTO involves down-regulation of JNK activation, inhibition of caspase-3 level, decrease in Bax and increase in Bcl-2 expression. Thus, TTO has a potential for use in the treatment of Parkinson’s disease.

scholarly journals Adenosine Receptors as Neuroinflammation Modulators: Role of A1 Agonists and A2A Antagonists

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1739
Author(s):  
Aleix Martí Navia ◽  
Diego Dal Ben ◽  
Catia Lambertucci ◽  
Andrea Spinaci ◽  
Rosaria Volpini ◽  
...  
Keyword(s):  
Partial Agonist ◽  
Pathological Condition ◽  
Neuroprotective Effect ◽  
Antioxidant Properties ◽  
Potential Candidate ◽  
In Vivo Models ◽  
Tnf Α

The pathological condition of neuroinflammation is caused by the activation of the neuroimmune cells astrocytes and microglia. The autacoid adenosine seems to be an important neuromodulator in this condition. Its main receptors involved in the neuroinflammation modulation are A1AR and A2AAR. Evidence suggests that A1AR activation produces a neuroprotective effect and A2AARs block prevents neuroinflammation. The aim of this work is to elucidate the effects of these receptors in neuroinflammation using the partial agonist 2′-dCCPA (2-chloro-N6-cyclopentyl-2′-deoxyadenosine) (C1 KiA1AR = 550 nM, KiA2AAR = 24,800 nM, and KiA3AR = 5560 nM, α = 0.70, EC50A1AR = 832 nM) and the newly synthesized in house compound 8-chloro-9-ethyl-2-phenethoxyadenine (C2 KiA2AAR = 0.75 nM; KiA1AR = 17 nM and KiA3AR = 227 nM, IC50A2AAR = 251 nM unpublished results). The experiments were performed in in vitro and in in vivo models of neuroinflammation. Results showed that C1 was able to prevent the inflammatory effect induced by cytokine cocktail (TNF-α, IL-1β, and IFN-γ) while C2 possess both anti-inflammatory and antioxidant properties, counteracting both neuroinflammation in mixed glial cells and in an animal model of neuroinflammation. In conclusion, C2 is a potential candidate for neuroinflammation therapy.

scholarly journals Neuroprotective Effect of the Marine-Derived Compound 11-Dehydrosinulariolide through DJ-1-Related Pathway in In Vitro and In Vivo Models of Parkinson’s Disease

Marine Drugs ◽  
2016 ◽  
Vol 14 (10) ◽  
pp. 187 ◽  
Author(s):  
Chien-Wei Feng ◽  
Han-Chun Hung ◽  
Shi-Ying Huang ◽  
Chun-Hong Chen ◽  
Yun-Ru Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroprotective Effect ◽  
In Vivo Models ◽  
Related Pathway

Recent Progress in Oleanolic Acid: Structural Modification and Biological Activity

2021 ◽  
Vol 21 ◽  
Author(s):  
Wang Wang ◽  
Yutong Li ◽  
Yan Li ◽  
Dejuan Sun ◽  
Hua Li ◽  
...  
Keyword(s):  
Oleanolic Acid ◽  
Structural Modification ◽  
Recent Progress ◽  
Biological Activities ◽  
Biological Effects ◽  
Biologically Active ◽  
In Vivo Models ◽  
Action Mechanisms

: Natural products have been proven as the main source of biologically active compounds, which are potentially useful for drug development. As one of the most studied pentacyclic triterpenes, oleanolic acid (OA) exhibits a broad range of biological activities and serves as a good scaffold for the development of novel derivatives that could be vital in drug discovery for various ailments. Up to now, many of its derivatives with multiple bioactivities have been prepared through chemical modification. This review summarizes the recent reports of OA derivatives (2016-present) and their biological effects and action mechanisms in vitro and in vivo models, and discusses the design of novel and potent derivatives.

scholarly journals Neuroprotective and Cognitive Enhancement Potentials of Baicalin: A Review

2018 ◽  
Vol 8 (6) ◽  
pp. 104 ◽  
Author(s):  
Kandhasamy Sowndhararajan ◽  
Ponnuvel Deepa ◽  
Minju Kim ◽  
Se Park ◽  
Songmun Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Cognitive Enhancement ◽  
Neuroprotective Effect ◽  
Neuroprotective Agents ◽  
Chinese Medicinal Herb ◽  
In Vivo Models ◽  
Flavonoid Compounds

Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the gradual loss of neurons. The development of effective neuroprotective agents to prevent and control neurodegenerative diseases is specifically important. Recently, there has been an increasing interest in selecting flavonoid compounds as potential neuroprotective agents, owing to their high effectiveness with low side effects. Baicalin is one of the important flavonoid compounds, which is mainly isolated from the root of Scutellaria baicalensis Georgi (an important Chinese medicinal herb). In recent years, a number of studies have shown that baicalin has a potent neuroprotective effect in various in vitro and in vivo models of neuronal injury. In particular, baicalin effectively prevents neurodegenerative diseases through various pharmacological mechanisms, including antioxidative stress, anti-excitotoxicity, anti-apoptotic, anti-inflammatory, stimulating neurogenesis, promoting the expression of neuronal protective factors, etc. This review mainly focuses on the neuroprotective and cognitive enhancement effects of baicalin. The aim of the present review is to compile all information in relation to the neuroprotective and cognitive enhancement effects of baicalin and its molecular mechanisms of action in various in vitro and in vivo experimental models.

scholarly journals Huang-Pu-Tong-Qiao Formula Ameliorates Tau Phosphorylation by Inhibiting the CaM-CaMKIV Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Shu Ye ◽  
Biao Cai ◽  
Peng Zhou ◽  
Guoquan Wang ◽  
Huawu Gao ◽  
...  
Keyword(s):  
Cell Viability ◽  
Learning And Memory ◽  
Neuronal Damage ◽  
Cell Model ◽  
Neuroprotective Effect ◽  
Tau Phosphorylation ◽  
Morris Water Maze Test ◽  
Mrna Levels

Alzheimer’s disease (AD) is a complex neurodegenerative disease. It is a chronic, lethal disease in which brain function is severely impaired and neuronal damage is irreversible. Huang-Pu-Tong-Qiao (HPTQ), a formula from traditional Chinese medicine, has been used in the clinical treatment of AD for many years, with remarkable effects. However, the neuroprotective mechanisms of HPTQ in AD have not yet been investigated. In the present study, we used AD models in vivo and in vitro, to investigate both the neuroprotective effect of HPTQ water extracts (HPTQ-W) and the potential mechanisms of this action. For the in vivo study, after HPTQ intervention, the Morris water maze test was used to examine learning and memory in rats. Transmission electron microscopy and immunofluorescence methods were then used to investigate neuronal damage. For the in vitro experiments, rat primary hippocampal neurons were cultured and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Additionally, mRNA levels of CaM, CaMKK, CaMKIV, and tau were examined using qRT-PCR, and protein expression of CaM, CaMKK, p-CaMKIV, and p-tau were examined using western blot. In vivo, we revealed that HPTQ significantly improved learning and memory deficits and attenuated neuronal damage in the AD rat model. Furthermore, in vitro results showed that HPTQ significantly increased cell viability in the AD cell model. We also demonstrated that HPTQ significantly decreased the mRNA levels of CaM, CaMKK, CaMKIV, and tau and significantly decreased the protein expressions of CaM, CaMKK, p-CaMKIV, and p-tau. In conclusion, our results indicated that HPTQ improved cognition and ameliorated neuronal damage in AD models and implicated a reduction in tau phosphorylation caused by inhibition of the CaM-CaMKIV pathway as a possible mechanism.

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