Huang-Lian-Jie-Du-Decoction （HLJDD） has been widely used for the treatment of Alzheimer＇s disease （AD） in clinic. However, the relationship between its chemical profile and neuroprotective bioactivity was not cle...Huang-Lian-Jie-Du-Decoction （HLJDD） has been widely used for the treatment of Alzheimer＇s disease （AD） in clinic. However, the relationship between its chemical profile and neuroprotective bioactivity was not clearly clarified yet. In present study, the water extract of HLJDD and subsequent three polarity fractions divided by different reagents were investigated. A total of 17 chromatographic peaks were confirmed by comparison with standards and their UV, MS spectra. Among them, 11 major compounds were determined by HPLC-DAD method with good linear regression relationship （r2, 0.9994-0.9999）, precisions （inter-day precision RSD, 0.79%-1.07%; intra-day precision RSD, 1.59%-2.10%）, repeatability （RSD, 1.66%-3.67%）, stability （RSD, 1.26%-4.77%） and recovery （95.24%-105.41%, RSD, 0.29%-2.69%）. Furthermore, PC12 cells and primary neurons cells were used for the neuroprotective effective assessment of aforementioned four samples from HLJDD. 3＂he total aqueous extract and n-butanol extract of HLJDD presented more significant effects than the other two parts. According to their quality and quantity determination results, iridoids and alkaloids have a positive correlation with the neuroprotective effectiveness of HLJDD.展开更多
Aim The enhanced effect of Bushen (Kidney-tonifying) decoction (BS) oncultured PC12 cell proliferation and its antagonistic action on neurotoxicity induced by glutamatewere investigated by serum pharmacological method...Aim The enhanced effect of Bushen (Kidney-tonifying) decoction (BS) oncultured PC12 cell proliferation and its antagonistic action on neurotoxicity induced by glutamatewere investigated by serum pharmacological method of the Chinese material medica (CMM) in vitro.Methods The effect of BS on cultured PC12 cell activity and its antagonistic action on neurotoxicityinduced by glutamate was observed by MTT method. Flow cytometry and fluorescence microscopetechniques were employed to observe the antagonistic effect of BS on early period apoptosis of PC12cells induced by glutamate. Results The serum with BS was able to enhance activity of PC12 cells andexert antagonistic effect on glutamate-induced neurotoxicity. Meanwhile, these beneficial effectsproduced by BS were found to be the strongest in 20% concentration of in serum BS. Moreover, it caninhibit apoptosis of PC12 cells induced by glutamate , which occurs in the early period. ConclusionBS may exert a potential neuroprotective effect.展开更多
Objective To investigate the pretreatment effects of Rhodiola rosea （R. rosea） extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer＇s disease ...Objective To investigate the pretreatment effects of Rhodiola rosea （R. rosea） extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer＇s disease （AD）. Methods Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin （1.5 mg/kg） on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde （MDA）, glutathione reductase （GR） and reduced glutathione （GSH） levels in hippocampus and histopathology of hippocampal neurons. Results The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract （3.0 g/kg）. Conclusion R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.展开更多
Previous studies have shown that berberine has neuroprotective effects against Alzheimer’s disease,including antagonizing tau phosphorylation,and inhibiting acetylcholinesterase activity and neural cell apoptosis.How...Previous studies have shown that berberine has neuroprotective effects against Alzheimer’s disease,including antagonizing tau phosphorylation,and inhibiting acetylcholinesterase activity and neural cell apoptosis.However,its low bioavailability and adverse reactions with conventional administration limit its clinical application.In this study,we prepared berberine nanoliposomes using liposomes characterized by low toxicity,high entrapment efficiency,and biodegradability,and modified them with lactoferrin.Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency.We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer’s disease established by injection of amyloid-beta 1-42 into the lateral ventricle.Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus,reduced tau over-phosphorylation in the cerebral cortex,and improved mouse behavior.These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer’s disease.展开更多
Epigallocatechin-3-gallate （EGCG）, a naturally occurring compound in green tea, has been widely used as an antioxidant agent. In the present study, model rats with acute spinal cord injury were intraperitoneally inj...Epigallocatechin-3-gallate （EGCG）, a naturally occurring compound in green tea, has been widely used as an antioxidant agent. In the present study, model rats with acute spinal cord injury were intraperitoneally injected with 25, 50, and 100 mg/kg EGCG, and spinal cord ultrastructure, oxidative stress reaction, inflammatory factors, and apoptosis-associated gene expression were observed. Results showed that EGCG attenuated neuronal and axonal injury 24 hours post injury. It also decreased serum intedeukin-113, tumor necrosis factor-a, and intercellular adhesion molecule-1 release, and decreased apoptosis-associated gene expression. Furthermore, it increased the level of the superoxide anion （O2-）, superoxide dismutase, and B-cell lymphoma/leukemia-2, and reduced malondialdehyde levels. Furthermore, it reduced the expression of the pro-apoptotic protein Bax. Noticeably, EGCG at the 100 mg/kg dosage exhibited similar effects as methylprednisolone sodium succinate, which has been frequently used for clinical acute spinal cord injury. The results demonstrated that EGCG can significantly inhibit inflammation, suppress oxidation, and reduce apoptosis in acute spinal cord injury.展开更多
A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer＇s disease （AD）. In particular, dysregulation of cholesterol homeostasis in the brain ...A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer＇s disease （AD）. In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β （Aβ） levels by affecting amyloid precursor protein （APP） cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD. Epidemiological studies also suggested that statin use is associated with a decreased incidence of AD. Therefore, statins are believed to be a good candidate for conferring neuropro- tective effects against AD. Statins may play a beneficial role in reducing A^-induced neurotoxicity. Their effect involves a putative mechanism beyond its cholesterol-lowering effects in preventing A[3-induced neurotoxicity. However, the underlying molecular mechanisms of the protective effect of statins have not been clearly determined in Aβ-induced neurotoxicity. Given that statins may provide benefits beyond the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A （HMG-CoA） reductase, these drugs may also improve the brain. Thus, statins may have beneficial effects on impaired insulin signaling by activating AMP-activated protein kinase （AMPK） in neuronal cells. They play a potential therapeutic role in targeting Aβ-mediated neurotoxicity.展开更多
There are few studies on the neuroprotective effects of syringaldehyde in a rat model of cerebral ischemia. The study aimed to elucidate the mechanisms underlying the neuroprotective effects of syringaldehyde on ische...There are few studies on the neuroprotective effects of syringaldehyde in a rat model of cerebral ischemia. The study aimed to elucidate the mechanisms underlying the neuroprotective effects of syringaldehyde on ischemic brain cells. Rat models of cerebral ischemia were intraperitoneally administered syringaldehyde. At 6 and 24 hours after syringaldehyde administration, cell damage in the brain of cerebral ischemia rats was obviously reduced, superoxide dismutase activity and nuclear respiratory factor 1 expression in the brain tissue were markedly increased, malondi-adehyde level was obviously decreased, apoptosis-related cysteine peptidase caspase-3 and -9 immunoreactivity was obviously decreased, and neurological function was markedly improved. These ifndings suggest that syringaldehyde exerts neuroprotective effects on cerebral ischemia injury through anti-oxidation and anti-apoptosis.展开更多
Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However,...Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.展开更多
Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop respondi...Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.展开更多
BACKGROUND Oxidative stress results in the production of excess reactive oxygen species(ROS)and triggers hippocampal neuronal damage as well as occupies a key role in the pathological mechanisms of neurodegenerative d...BACKGROUND Oxidative stress results in the production of excess reactive oxygen species(ROS)and triggers hippocampal neuronal damage as well as occupies a key role in the pathological mechanisms of neurodegenerative disorders such as Alzheimer’s disease(AD).A recent study confirmed that magnesium had an inhibitory effect against oxidative stress-related malondialdehyde in vitro.However,whether Magnesium-L-threonate(MgT)is capable of suppressing oxidative stress damage in amyloidβ(Aβ)_(25-35)-treated HT22 cells and the AD mouse model still remains to be investigated.AIM To explore the neuroprotective effect of MgT against oxidative stress injury in vitro and in vivo,and investigate the mechanism.METHODS Aβ_(25-35)-induced HT22 cells were preconditioned with MgT for 12 h.APPswe/PS1dE9(APP/PS1)mice were orally administered with MgT daily for 3 mo.After MgT treatment,the viability of Aβ_(25-35)-treated HT22 cells was determined via conducting cell counting kit-8 test and the cognition of APP/PS1 mice was measured through the Morris Water Maze.Flow cytometry experiments were applied to assess the ROS levels of HT22 cells and measure the apoptosis rate of HT22 cells or hippocampal neurons.Expression of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X(Bax),hypoxiainducible factor(HIF)-1α,NADPH oxidase(NOX)4,Aβ_(1-42) and phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)pathway proteins was quantified by Western blot.RESULTS In vitro data confirmed that Aβ_(25-35)-induced HT22 cells had a significantly lower cell viability,higher ROS level and higher apoptosis rates compared with those of control cells(all P<0.001).MgT prevented the Aβ_(25-35)-triggered oxidative stress damage by elevating viability and decreasing ROS formation and apoptosis of HT22 cells(all P<0.001).APP/PS1 mice exhibited worse cognitive performance and higher apoptosis rate of hippocampal neurons than wild-type(WT)mice(all P<0.01).Meanwhile,significant higher expression of Aβ_(1-42) and NOX4 proteins was detected in APP/PS1 mice than those of WT mice(both P<0.01).MgT also ameliorated the cognitive deficit,suppressed the apoptosis of hippocampal neuron and downregulated the expression of Aβ_(1-42) and NOX4 proteins in APP/PS1 mouse(all P<0.05).Moreover,MgT intervention significantly downregulated HIF-1αand Bax,upregulated Bcl-2 and activated the PI3K/Akt pathway both in vitro and in vivo(all P<0.05).CONCLUSION MgT exhibits neuroprotective effects against oxidative stress and hippocampal neuronal apoptosis in Aβ_(25-35)-treated HT22 cells and APP/PS1 mice.展开更多
Multiple sclerosis（MS）is a chronic autoimmune disease of the central nervous system（CNS）characterized by coexisting processes of inflammation,demyelination,axonal neurodegeneration,and gliosis.It is the most commo...Multiple sclerosis（MS）is a chronic autoimmune disease of the central nervous system（CNS）characterized by coexisting processes of inflammation,demyelination,axonal neurodegeneration,and gliosis.It is the most common disabling neurological disease in young adulthood.展开更多
In our previous study, defatted walnut meal hydrolysate(DWMH) could attenuate D-galactose-induced acute memory deficits in vivo, and six potent active peptides including WSREEQ, WSREEQE, WSREEQEREE, ADIYTE, ADIYTEEAG ...In our previous study, defatted walnut meal hydrolysate(DWMH) could attenuate D-galactose-induced acute memory deficits in vivo, and six potent active peptides including WSREEQ, WSREEQE, WSREEQEREE, ADIYTE, ADIYTEEAG and ADIYTEEAGR were identified. The aim of this study was to investigate the possible mechanism underlying their neuroprotective effects on glutamate-induced apoptosis in PC12 cells and their digestive stability. Results showed that all these peptides could attenuate the reduction of cell viability caused by glutamate in PC12 cells, especially WSREEQEREE and ADIYTEEAGR. The addition of Arg residue in WSREEQEREE and ADIYTEEAGR might be the potential reason for their stronger protective effects. Additionally, these two peptides possibly protected PC12 cells against glutamate-induced apoptosis via activating intracellular antioxidant defence(superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px)) through Kelch-like ECH-associated protein 1(Keap1) inhibition, inhibiting ROS production, Ca;influx and mitochondrial membrane potential(MMP) collapse as well as regulating the expression of apoptosis-related proteins(Bax and Bcl-2). This might be due to the presence of Trp, Tyr and Arg in these two peptides. However, encapsulation of WSREEQEREE and ADIYTEEAGR should be considered based on their digestive sensibility during in vitro gastrointestinal digestion.展开更多
Five undescribed sesquiterpenoids(1–5),and nine known sesquiterpenoids(6–14)were obtained from the fruits of Litsea lancilimba Merr.by LC-MS/MS molecular networking strategies.Litsemene A(1)possessed a unique 8-memb...Five undescribed sesquiterpenoids(1–5),and nine known sesquiterpenoids(6–14)were obtained from the fruits of Litsea lancilimba Merr.by LC-MS/MS molecular networking strategies.Litsemene A(1)possessed a unique 8-member ring through unexpected cyclization of the methyl group on C-10 of guaiane.Their structures were elucidated by spectroscopic techniques including IR,UV,NMR,HR-ESI-MS,and their absolute configurations were assigned by ECD calculations.All isolated sesquiterpenoids were analyzed by bioinformatics and evaluated for their neuroprotective effects against H_(2)O_(2)-induced injury in human neuroblastoma SH-SY5Y cells.展开更多
Exposure to mercury can cause immune, sensory, neurological, motor and behavioral dysfunctions similar to traits associated with autism spectrum disorders （ASDs）, and these similarities extend to neuroanatomy, neuro...Exposure to mercury can cause immune, sensory, neurological, motor and behavioral dysfunctions similar to traits associated with autism spectrum disorders （ASDs）, and these similarities extend to neuroanatomy, neurotransmitters and biochemistry. It also affects antioxidant system in the cell, resulting in loss of membrane integrity and finally cellular necrosis （Abdel Moneim, 2015）.展开更多
Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2：1：2 and dissolved in pure water, is neuroprotective in animal models of various ...Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2：1：2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8（SAMP8） mice（a model of Alzheimer＇s disease） at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer＇s disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer＇s disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.展开更多
Epidemiologic studies often consider gender differences in a particular pathology, and constantly observe variations between men and wom- en. Indeed, a remarkable sexual dimorphism exists in the epidemiology of neurol...Epidemiologic studies often consider gender differences in a particular pathology, and constantly observe variations between men and wom- en. Indeed, a remarkable sexual dimorphism exists in the epidemiology of neurological conditions and brain diseases. Physiologically, males and females differ by their levels of circulating hormones that drive sexual behavioral, as well as endocrine functions. Estrogen is the pri- mary female sex hormonal group that enwraps estradiol, estrone and estriol, and which are the major naturally occurring hormones preva- lent in women. Their role in the reproductive function has long been established, although the ubiquitous expression of its receptors （alpha, beta and G protein-coupled, GPR30） presumes a broader spectrum of action. This short review will summarize the current knowledge in estrogen therapy with particular focus on some of the recent work that might lead to new neuroprotective treatments.展开更多
Objective:Swertia pseudochinensis,an annual herb of the genus Swertia in the family Gentianaceae.Some constituents and extracts from the Swertia genus have been recently reported to possess neuroprotective effects,sug...Objective:Swertia pseudochinensis,an annual herb of the genus Swertia in the family Gentianaceae.Some constituents and extracts from the Swertia genus have been recently reported to possess neuroprotective effects,suggesting their potential utility in the prevention and treatment of Parkinson disease(PD).The aim of this work is to identify the chemical constituents and evaluate the potential biological activists of Swertia pseudochinensis.Methods:The phytochemicals from the aerial parts of S.pseudochinensis were isolated and purified by silica gel,Sephadex LH-20 gel,semi-preparative high-performance liquid chromatography,and identified by the spectroscopic methods.All compounds were evaluated for their potential neuroprotective effects against 1-methyl-4-phenylpyridinium-induced apoptosis in the SH-SY5Y human neuroblastoma cell line using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay.Then,we performed an enrichment analysis using the Database for Annotation,Visualization,and Integrated Discovery and investigated the mechanisms by which bellidifolin regulates neurodegenerative disease.Results:Two new anthraquinone,1,5,6-trimethoxy-2-hydroxy-3-methy-anthraquinone(1)and 1,5,6,8-tetramethoxy-2-hydroxy-3-methyanthraquinone(2),together with nine known including 7-O-b-d-glucopyranosyl-1,8-dihydroxy-3-methoxyxanthone(3),gentisin(4),swertianolin(5),bellidifolin(6),gentiacaulein(7),norswertianolin(8),5-O-b-d-glucopyranosyl-1,3,8-trihydroxyapatone(9),1-hydroxy-3,5,8-trimethoxyxanthone(10),and aurantio-obtusin(11),were isolated and compounds 6–8 and 10 exhibited neuroprotective effects at a concentration of 50mmol/L.Among them,bellidifolin showed significant protective activity,and might have potential as a neuroprotective agent for the treatment of PD,possibly by acting on oxidative damage and reactive oxygen species.Conclusions:These findings indicate that further research on the genus Swertia and its bioactive constituents toward neurodegenerative disorders could be extremely rewarding.展开更多
Neurodegenerative diseases affect millions of individuals worldwide.It has been estimated that the number of patients affected by neurodegenerative diseases such as Alzheimer’s disease（AD）,Parkinson’s disease（PD...Neurodegenerative diseases affect millions of individuals worldwide.It has been estimated that the number of patients affected by neurodegenerative diseases such as Alzheimer’s disease（AD）,Parkinson’s disease（PD）,Huntington’s disease（HD）,展开更多
OBJECTIVE URB597(KDS-4103)is a potent and selective inhibitor of the enzyme fatty acid amide hydrolase(FAAH)and can ele⁃vate the level of oleoylethanolamide(OEA),a naturally occurring endocannabinoid in the brain.Howe...OBJECTIVE URB597(KDS-4103)is a potent and selective inhibitor of the enzyme fatty acid amide hydrolase(FAAH)and can ele⁃vate the level of oleoylethanolamide(OEA),a naturally occurring endocannabinoid in the brain.However,the effect of URB597 on cerebral isch⁃emic injury in mice remains unclear.METHODS Focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min followed by reperfusion for 24 h in mice.To observe the dose-dependent effect,URB597(0.04-5.00 mg·kg-1,ip)was administered at the same time of reperfu⁃sion.To determine the time-dependent effect,URB597(1.00 mg·kg-1,ip)was administered as a single dose at 0,1,3 or 5 h after reperfusion.Twenty-four hours after brain ischemia,Beder⁃son scoring test and grip strength test were used to evaluate the neurological function;brain in⁃farct volume was assayed by 2,3,5-triphenyltetra⁃zolium chloride(TTC)staining or diffusion-weighted magnetic resonance imaging(MRI).Laser speckle imaging(LSI)technique was used to assay the regional cerebral blood flow(rCBF);NeuN immunofluorescence staining was used to observe the neuron survival in the penumbra.To further investigate the underlying mechanism,au⁃tophagy flux related proteins(LC3-Ⅱ,P62 and LAMP2)and necroptosis related proteins(pRIPK3 and pMLKL)were detected by Western blotting and immunofluorescence staining.RESULTS Twenty-four hours after brain ischemia,URB597 dose-dependently improved neurological func⁃tion and reduced brain infarct volume.The most effective dose was 1.00 mg·kg-1;the therapeutic time window was within 1 h after ischemic stroke.The protective effect is further confirmed by the results that post-ischemic treatment with URB597(1.00 mg·kg-1)significantly increased neurons survival,promoted autophagy flux and reduced cell necroptosis in cortical penumbra after cerebral I/R.CONCLUSION URB597 dose-and time-dependently exerts a neuroprotective effect against acute cerebral I/R injury.This neu⁃roprotective effect of URB597 may be associated with its restoration of autophagy flux and inhibi⁃tion of neuronal necroptosis in the cortical penumbra.展开更多
Cerebrovascular accident（CVA）or stroke is one of the world＇s leading causes of death and permanent disability.The high social and medical costs associated with this pathology mean there is an urgent need to find ef...Cerebrovascular accident（CVA）or stroke is one of the world＇s leading causes of death and permanent disability.The high social and medical costs associated with this pathology mean there is an urgent need to find effective therapies.Occlusion of the middle cerebral artery（MCAO）,mainly by clots,is the origin of most CVAs in humans.展开更多
基金Key Projects in the National Science & Technology Pillar Program during the 11thFive-Year Plan Period (Grant No.2008BAI51B02)National Natural Science Fund Project of China (Grant No. 81202904)
文摘Huang-Lian-Jie-Du-Decoction （HLJDD） has been widely used for the treatment of Alzheimer＇s disease （AD） in clinic. However, the relationship between its chemical profile and neuroprotective bioactivity was not clearly clarified yet. In present study, the water extract of HLJDD and subsequent three polarity fractions divided by different reagents were investigated. A total of 17 chromatographic peaks were confirmed by comparison with standards and their UV, MS spectra. Among them, 11 major compounds were determined by HPLC-DAD method with good linear regression relationship （r2, 0.9994-0.9999）, precisions （inter-day precision RSD, 0.79%-1.07%; intra-day precision RSD, 1.59%-2.10%）, repeatability （RSD, 1.66%-3.67%）, stability （RSD, 1.26%-4.77%） and recovery （95.24%-105.41%, RSD, 0.29%-2.69%）. Furthermore, PC12 cells and primary neurons cells were used for the neuroprotective effective assessment of aforementioned four samples from HLJDD. 3＂he total aqueous extract and n-butanol extract of HLJDD presented more significant effects than the other two parts. According to their quality and quantity determination results, iridoids and alkaloids have a positive correlation with the neuroprotective effectiveness of HLJDD.
基金National Natural Science Foundation of Shanxi Province(No:19991091) and HiTech Resereh and Development Program of China (No:2004AA2Z3815)
文摘Aim The enhanced effect of Bushen (Kidney-tonifying) decoction (BS) oncultured PC12 cell proliferation and its antagonistic action on neurotoxicity induced by glutamatewere investigated by serum pharmacological method of the Chinese material medica (CMM) in vitro.Methods The effect of BS on cultured PC12 cell activity and its antagonistic action on neurotoxicityinduced by glutamate was observed by MTT method. Flow cytometry and fluorescence microscopetechniques were employed to observe the antagonistic effect of BS on early period apoptosis of PC12cells induced by glutamate. Results The serum with BS was able to enhance activity of PC12 cells andexert antagonistic effect on glutamate-induced neurotoxicity. Meanwhile, these beneficial effectsproduced by BS were found to be the strongest in 20% concentration of in serum BS. Moreover, it caninhibit apoptosis of PC12 cells induced by glutamate , which occurs in the early period. ConclusionBS may exert a potential neuroprotective effect.
文摘Objective To investigate the pretreatment effects of Rhodiola rosea （R. rosea） extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer＇s disease （AD）. Methods Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin （1.5 mg/kg） on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde （MDA）, glutathione reductase （GR） and reduced glutathione （GSH） levels in hippocampus and histopathology of hippocampal neurons. Results The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract （3.0 g/kg）. Conclusion R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.
基金financially supported by Shenzhen Sanming Project of Medicine and Health, No. SZSM201612049 (to KJC)the Shenzhen Municipal Basic Research Project for Discipline Layout of China, No. JCYJ20170413161352000 (to YHL)Guangdong Basic Research Project, No. 2020A1515011427 (to ZZW)
文摘Previous studies have shown that berberine has neuroprotective effects against Alzheimer’s disease,including antagonizing tau phosphorylation,and inhibiting acetylcholinesterase activity and neural cell apoptosis.However,its low bioavailability and adverse reactions with conventional administration limit its clinical application.In this study,we prepared berberine nanoliposomes using liposomes characterized by low toxicity,high entrapment efficiency,and biodegradability,and modified them with lactoferrin.Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency.We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer’s disease established by injection of amyloid-beta 1-42 into the lateral ventricle.Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus,reduced tau over-phosphorylation in the cerebral cortex,and improved mouse behavior.These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer’s disease.
文摘Epigallocatechin-3-gallate （EGCG）, a naturally occurring compound in green tea, has been widely used as an antioxidant agent. In the present study, model rats with acute spinal cord injury were intraperitoneally injected with 25, 50, and 100 mg/kg EGCG, and spinal cord ultrastructure, oxidative stress reaction, inflammatory factors, and apoptosis-associated gene expression were observed. Results showed that EGCG attenuated neuronal and axonal injury 24 hours post injury. It also decreased serum intedeukin-113, tumor necrosis factor-a, and intercellular adhesion molecule-1 release, and decreased apoptosis-associated gene expression. Furthermore, it increased the level of the superoxide anion （O2-）, superoxide dismutase, and B-cell lymphoma/leukemia-2, and reduced malondialdehyde levels. Furthermore, it reduced the expression of the pro-apoptotic protein Bax. Noticeably, EGCG at the 100 mg/kg dosage exhibited similar effects as methylprednisolone sodium succinate, which has been frequently used for clinical acute spinal cord injury. The results demonstrated that EGCG can significantly inhibit inflammation, suppress oxidation, and reduce apoptosis in acute spinal cord injury.
基金supported by the grants from the Ministry of Science and Technology of Taiwan,China(MOST 105-2314-B-013-MY3 and MOST 106-2320-B-040-021-MY3)
文摘A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer＇s disease （AD）. In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β （Aβ） levels by affecting amyloid precursor protein （APP） cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD. Epidemiological studies also suggested that statin use is associated with a decreased incidence of AD. Therefore, statins are believed to be a good candidate for conferring neuropro- tective effects against AD. Statins may play a beneficial role in reducing A^-induced neurotoxicity. Their effect involves a putative mechanism beyond its cholesterol-lowering effects in preventing A[3-induced neurotoxicity. However, the underlying molecular mechanisms of the protective effect of statins have not been clearly determined in Aβ-induced neurotoxicity. Given that statins may provide benefits beyond the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A （HMG-CoA） reductase, these drugs may also improve the brain. Thus, statins may have beneficial effects on impaired insulin signaling by activating AMP-activated protein kinase （AMPK） in neuronal cells. They play a potential therapeutic role in targeting Aβ-mediated neurotoxicity.
文摘There are few studies on the neuroprotective effects of syringaldehyde in a rat model of cerebral ischemia. The study aimed to elucidate the mechanisms underlying the neuroprotective effects of syringaldehyde on ischemic brain cells. Rat models of cerebral ischemia were intraperitoneally administered syringaldehyde. At 6 and 24 hours after syringaldehyde administration, cell damage in the brain of cerebral ischemia rats was obviously reduced, superoxide dismutase activity and nuclear respiratory factor 1 expression in the brain tissue were markedly increased, malondi-adehyde level was obviously decreased, apoptosis-related cysteine peptidase caspase-3 and -9 immunoreactivity was obviously decreased, and neurological function was markedly improved. These ifndings suggest that syringaldehyde exerts neuroprotective effects on cerebral ischemia injury through anti-oxidation and anti-apoptosis.
基金the National Basic Research Program of China(973Program),No.2007CB512601Science and Technology Development Plan of TCM in Shandong Province,No.2009-006Science and Technology Plan in Colleges and Universities of Shandong Province,No.J11LF60,J11LF08
文摘Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.
文摘Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.
基金Supported by National Natural Science Foundation of China,No. 81870836Natural Science Foundation of Guangdong Province,China,No. 2020A1515010210+1 种基金Science and Technology Program of Guangzhou,China,No. 202007030010Guangdong Basic and Applied Basic Research Foundation,China,No. 2020A1515110317 and No. 2021A1515010705
文摘BACKGROUND Oxidative stress results in the production of excess reactive oxygen species(ROS)and triggers hippocampal neuronal damage as well as occupies a key role in the pathological mechanisms of neurodegenerative disorders such as Alzheimer’s disease(AD).A recent study confirmed that magnesium had an inhibitory effect against oxidative stress-related malondialdehyde in vitro.However,whether Magnesium-L-threonate(MgT)is capable of suppressing oxidative stress damage in amyloidβ(Aβ)_(25-35)-treated HT22 cells and the AD mouse model still remains to be investigated.AIM To explore the neuroprotective effect of MgT against oxidative stress injury in vitro and in vivo,and investigate the mechanism.METHODS Aβ_(25-35)-induced HT22 cells were preconditioned with MgT for 12 h.APPswe/PS1dE9(APP/PS1)mice were orally administered with MgT daily for 3 mo.After MgT treatment,the viability of Aβ_(25-35)-treated HT22 cells was determined via conducting cell counting kit-8 test and the cognition of APP/PS1 mice was measured through the Morris Water Maze.Flow cytometry experiments were applied to assess the ROS levels of HT22 cells and measure the apoptosis rate of HT22 cells or hippocampal neurons.Expression of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X(Bax),hypoxiainducible factor(HIF)-1α,NADPH oxidase(NOX)4,Aβ_(1-42) and phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)pathway proteins was quantified by Western blot.RESULTS In vitro data confirmed that Aβ_(25-35)-induced HT22 cells had a significantly lower cell viability,higher ROS level and higher apoptosis rates compared with those of control cells(all P<0.001).MgT prevented the Aβ_(25-35)-triggered oxidative stress damage by elevating viability and decreasing ROS formation and apoptosis of HT22 cells(all P<0.001).APP/PS1 mice exhibited worse cognitive performance and higher apoptosis rate of hippocampal neurons than wild-type(WT)mice(all P<0.01).Meanwhile,significant higher expression of Aβ_(1-42) and NOX4 proteins was detected in APP/PS1 mice than those of WT mice(both P<0.01).MgT also ameliorated the cognitive deficit,suppressed the apoptosis of hippocampal neuron and downregulated the expression of Aβ_(1-42) and NOX4 proteins in APP/PS1 mouse(all P<0.05).Moreover,MgT intervention significantly downregulated HIF-1αand Bax,upregulated Bcl-2 and activated the PI3K/Akt pathway both in vitro and in vivo(all P<0.05).CONCLUSION MgT exhibits neuroprotective effects against oxidative stress and hippocampal neuronal apoptosis in Aβ_(25-35)-treated HT22 cells and APP/PS1 mice.
基金Dr.Mao-Draayer has served as a consultant and/or received grant support from:Acorda,Bayer Pharmaceutical,Biogen Idec,EMD Serono,Genzyme,Novartis,Questor,Teva Neuroscience and Chugai PharmaDr.Mao-Draayeris currently supported by grants from NIH NIAID Autoimmune Center of Excellence:UM1-AI110557+1 种基金NIH NINDS R01-NS080821the University of Michigan Neurology Department
文摘Multiple sclerosis（MS）is a chronic autoimmune disease of the central nervous system（CNS）characterized by coexisting processes of inflammation,demyelination,axonal neurodegeneration,and gliosis.It is the most common disabling neurological disease in young adulthood.
基金supported by the Taishan Industry Leading Talent Project, Guangdong Provincial Key R&D Program (2020B020226005)the Specific Fund Program for Basic and Applied Basic Research of Guangdong Province (2019A1515011952)+2 种基金the Fundamental Research Funds for the Central Universities (No. x2skD2192510)the Natural Science Foundation of Guangdong for Basic and Applied Basic Research (2020A1515010659)Special Support Project of Guangxi Province for Innovation driven Development (Guangdong Huapeptides Biotechnology Co., Ltd., AA17204075)。
文摘In our previous study, defatted walnut meal hydrolysate(DWMH) could attenuate D-galactose-induced acute memory deficits in vivo, and six potent active peptides including WSREEQ, WSREEQE, WSREEQEREE, ADIYTE, ADIYTEEAG and ADIYTEEAGR were identified. The aim of this study was to investigate the possible mechanism underlying their neuroprotective effects on glutamate-induced apoptosis in PC12 cells and their digestive stability. Results showed that all these peptides could attenuate the reduction of cell viability caused by glutamate in PC12 cells, especially WSREEQEREE and ADIYTEEAGR. The addition of Arg residue in WSREEQEREE and ADIYTEEAGR might be the potential reason for their stronger protective effects. Additionally, these two peptides possibly protected PC12 cells against glutamate-induced apoptosis via activating intracellular antioxidant defence(superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px)) through Kelch-like ECH-associated protein 1(Keap1) inhibition, inhibiting ROS production, Ca;influx and mitochondrial membrane potential(MMP) collapse as well as regulating the expression of apoptosis-related proteins(Bax and Bcl-2). This might be due to the presence of Trp, Tyr and Arg in these two peptides. However, encapsulation of WSREEQEREE and ADIYTEEAGR should be considered based on their digestive sensibility during in vitro gastrointestinal digestion.
基金supported by the National Natural Science Foundation of China(No.U1812403)the Science and Technology Planning Project of Liaoning Province(No.2021JH1/10400049).
文摘Five undescribed sesquiterpenoids(1–5),and nine known sesquiterpenoids(6–14)were obtained from the fruits of Litsea lancilimba Merr.by LC-MS/MS molecular networking strategies.Litsemene A(1)possessed a unique 8-member ring through unexpected cyclization of the methyl group on C-10 of guaiane.Their structures were elucidated by spectroscopic techniques including IR,UV,NMR,HR-ESI-MS,and their absolute configurations were assigned by ECD calculations.All isolated sesquiterpenoids were analyzed by bioinformatics and evaluated for their neuroprotective effects against H_(2)O_(2)-induced injury in human neuroblastoma SH-SY5Y cells.
文摘Exposure to mercury can cause immune, sensory, neurological, motor and behavioral dysfunctions similar to traits associated with autism spectrum disorders （ASDs）, and these similarities extend to neuroanatomy, neurotransmitters and biochemistry. It also affects antioxidant system in the cell, resulting in loss of membrane integrity and finally cellular necrosis （Abdel Moneim, 2015）.
基金funded by the National Natural Science Foundation of China,No.81473742the Guangdong Science and Technology Foundation,No.2013B021800101the Shenzhen Major Project of Science and Technology Planning,No.JCYJ20130401115231337
文摘Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2：1：2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8（SAMP8） mice（a model of Alzheimer＇s disease） at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer＇s disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer＇s disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.
文摘Epidemiologic studies often consider gender differences in a particular pathology, and constantly observe variations between men and wom- en. Indeed, a remarkable sexual dimorphism exists in the epidemiology of neurological conditions and brain diseases. Physiologically, males and females differ by their levels of circulating hormones that drive sexual behavioral, as well as endocrine functions. Estrogen is the pri- mary female sex hormonal group that enwraps estradiol, estrone and estriol, and which are the major naturally occurring hormones preva- lent in women. Their role in the reproductive function has long been established, although the ubiquitous expression of its receptors （alpha, beta and G protein-coupled, GPR30） presumes a broader spectrum of action. This short review will summarize the current knowledge in estrogen therapy with particular focus on some of the recent work that might lead to new neuroprotective treatments.
基金financially supported by the Liaoning Revitalization Talents Program(No.XLYC1807182)the Liaoning Province Natural Science Foundation(No.2019-MS-299).
文摘Objective:Swertia pseudochinensis,an annual herb of the genus Swertia in the family Gentianaceae.Some constituents and extracts from the Swertia genus have been recently reported to possess neuroprotective effects,suggesting their potential utility in the prevention and treatment of Parkinson disease(PD).The aim of this work is to identify the chemical constituents and evaluate the potential biological activists of Swertia pseudochinensis.Methods:The phytochemicals from the aerial parts of S.pseudochinensis were isolated and purified by silica gel,Sephadex LH-20 gel,semi-preparative high-performance liquid chromatography,and identified by the spectroscopic methods.All compounds were evaluated for their potential neuroprotective effects against 1-methyl-4-phenylpyridinium-induced apoptosis in the SH-SY5Y human neuroblastoma cell line using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay.Then,we performed an enrichment analysis using the Database for Annotation,Visualization,and Integrated Discovery and investigated the mechanisms by which bellidifolin regulates neurodegenerative disease.Results:Two new anthraquinone,1,5,6-trimethoxy-2-hydroxy-3-methy-anthraquinone(1)and 1,5,6,8-tetramethoxy-2-hydroxy-3-methyanthraquinone(2),together with nine known including 7-O-b-d-glucopyranosyl-1,8-dihydroxy-3-methoxyxanthone(3),gentisin(4),swertianolin(5),bellidifolin(6),gentiacaulein(7),norswertianolin(8),5-O-b-d-glucopyranosyl-1,3,8-trihydroxyapatone(9),1-hydroxy-3,5,8-trimethoxyxanthone(10),and aurantio-obtusin(11),were isolated and compounds 6–8 and 10 exhibited neuroprotective effects at a concentration of 50mmol/L.Among them,bellidifolin showed significant protective activity,and might have potential as a neuroprotective agent for the treatment of PD,possibly by acting on oxidative damage and reactive oxygen species.Conclusions:These findings indicate that further research on the genus Swertia and its bioactive constituents toward neurodegenerative disorders could be extremely rewarding.
文摘Neurodegenerative diseases affect millions of individuals worldwide.It has been estimated that the number of patients affected by neurodegenerative diseases such as Alzheimer’s disease（AD）,Parkinson’s disease（PD）,Huntington’s disease（HD）,
基金National Natural Science Foundation of China(81603093)and the Open Research Fund of State Key Laboratory of Cellu⁃lar Stress Biology,Xiamen University(SKLC⁃SB2019KF016)。
文摘OBJECTIVE URB597(KDS-4103)is a potent and selective inhibitor of the enzyme fatty acid amide hydrolase(FAAH)and can ele⁃vate the level of oleoylethanolamide(OEA),a naturally occurring endocannabinoid in the brain.However,the effect of URB597 on cerebral isch⁃emic injury in mice remains unclear.METHODS Focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min followed by reperfusion for 24 h in mice.To observe the dose-dependent effect,URB597(0.04-5.00 mg·kg-1,ip)was administered at the same time of reperfu⁃sion.To determine the time-dependent effect,URB597(1.00 mg·kg-1,ip)was administered as a single dose at 0,1,3 or 5 h after reperfusion.Twenty-four hours after brain ischemia,Beder⁃son scoring test and grip strength test were used to evaluate the neurological function;brain in⁃farct volume was assayed by 2,3,5-triphenyltetra⁃zolium chloride(TTC)staining or diffusion-weighted magnetic resonance imaging(MRI).Laser speckle imaging(LSI)technique was used to assay the regional cerebral blood flow(rCBF);NeuN immunofluorescence staining was used to observe the neuron survival in the penumbra.To further investigate the underlying mechanism,au⁃tophagy flux related proteins(LC3-Ⅱ,P62 and LAMP2)and necroptosis related proteins(pRIPK3 and pMLKL)were detected by Western blotting and immunofluorescence staining.RESULTS Twenty-four hours after brain ischemia,URB597 dose-dependently improved neurological func⁃tion and reduced brain infarct volume.The most effective dose was 1.00 mg·kg-1;the therapeutic time window was within 1 h after ischemic stroke.The protective effect is further confirmed by the results that post-ischemic treatment with URB597(1.00 mg·kg-1)significantly increased neurons survival,promoted autophagy flux and reduced cell necroptosis in cortical penumbra after cerebral I/R.CONCLUSION URB597 dose-and time-dependently exerts a neuroprotective effect against acute cerebral I/R injury.This neu⁃roprotective effect of URB597 may be associated with its restoration of autophagy flux and inhibi⁃tion of neuronal necroptosis in the cortical penumbra.
文摘Cerebrovascular accident（CVA）or stroke is one of the world＇s leading causes of death and permanent disability.The high social and medical costs associated with this pathology mean there is an urgent need to find effective therapies.Occlusion of the middle cerebral artery（MCAO）,mainly by clots,is the origin of most CVAs in humans.
