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
DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-bu...DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-butylphthalide action by various means.We used hydrogen peroxide to induce injury to PC12cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of DI-3-n-butylphthalide.We found that DI-3-nbutylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis.Furthermore,DI-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3.DI-3-nbutylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α,the key transcription factor that regulates Bax and Bnip3 genes.These findings suggest that DI-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.展开更多
The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have benefi...The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects.In this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic inflammation.This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area.We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia.Moreover,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal sprouting.However,this treatment decreased the formation of neuronal progenitor cells.This study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.展开更多
Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors,and which may be mediated by extracellular vesicles(or exosomes)released by mesenchymal stem cells.To investigate ...Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors,and which may be mediated by extracellular vesicles(or exosomes)released by mesenchymal stem cells.To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma,we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma.One week after injury,extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity.We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage,increased the number of retinal ganglion cells,and inhibited the activation of caspase-3.These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension,and this effect is achieved by inhibiting cell apoptosis.展开更多
Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotro...Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.展开更多
Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations....Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations.In addition,the survival,differentiation,and proliferation rates of transplanted exogenous NSCs are low,which limit their clinical application.Our previous study showed that neuregulin1β(NRG1β)alleviated cerebral I/R injury in rats.In this study,we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1βon PC12 cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R).Our results found that 5 and 10 nM NRG1βpromoted the generation and proliferation of NSCs.Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1βimproved the level of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,nicotinamide adenine dinucleotide phosphate,and nuclear factor erythroid 2-related factor 2(Nrf2)and mitochondrial damage in injured PC12 cells;these indexes are related to ferroptosis.Research has reported that p53 and solute carrier family 7 member 11(SLC7A11)play vital roles in ferroptosis caused by cerebral I/R injury.Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4(GPX4)was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells,but this change was alleviated after co-culturing NSCs with damaged PC12 cells.These findings suggest that NSCs pretreated with NRG1βexhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.展开更多
Sphingosine-1-phosphate receptor(S1PR)signaling regulates diverse pathophysiological processes in the central nervous system.The role of S1PR signaling in neurodegenerative conditions is still largely unidentified.Sip...Sphingosine-1-phosphate receptor(S1PR)signaling regulates diverse pathophysiological processes in the central nervous system.The role of S1PR signaling in neurodegenerative conditions is still largely unidentified.Siponimod is a specific modulator of S1P1 and S1P5 receptors,an immunosuppressant drug for managing secondary progressive multiple sclerosis.We investigated its neuroprotective properties in vivo on the retina and the brain in an optic nerve injury model induced by a chronic increase in intraocular pressure or acute N-methyl-D-aspartate excitotoxicity.Neuronal-specific deletion of sphingosine-1-phosphate receptor(S1PR1)was carried out by expressing AAV-PHP.eB-Cre recombinase under Syn1 promoter in S1PR1mice to define the role of S1PR1 in neurons.Inner retinal electrophysiological responses,along with histological and immunofluorescence analysis of the retina and optic nerve tissues,indicated significant neuroprotective effects of siponimod when administered orally via diet in chronic and acute optic nerve injury models.Further,siponimod treatment showed significant protection against trans-neuronal degenerative changes in the higher visual center of the brain induced by optic nerve injury.Siponimod treatment also reduced microglial activation and reactive gliosis along the visual pathway.Our results showed that siponimod markedly upregulated neuroprotective Akt and Erk1/2 activation in the retina and the brain.Neuronal-specific deletion of S1PR1 enhanced retinal and dorsolateral geniculate nucleus degenerative changes in a chronic optic nerve injury condition and attenuated protective effects of siponimod.In summary,our data demonstrated that S1PR1signaling plays a vital role in the retinal ganglion cell and dorsolateral geniculate nucleus neuronal survival in experimental glaucoma,and siponimod exerts direct neuroprotective effects through S1PR1 in neurons in the central nervous system independent of its peripheral immuno-modulatory effects.Our findings suggest that neuronal S1PR1 is a neuroprotective therapeutic target and its modulation by siponimod has positive implications in glaucoma conditions.展开更多
Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release o...Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.展开更多
Glaucoma results from irreversible loss of retinal ganglion cells(RGCs)through an unclear mechanism.Microglial polarization and neuroinflammation play an important role in retinal degeneration.Our study aimed to explo...Glaucoma results from irreversible loss of retinal ganglion cells(RGCs)through an unclear mechanism.Microglial polarization and neuroinflammation play an important role in retinal degeneration.Our study aimed to explore the function of microglial polarization during glaucoma progression and identify a strategy to alleviate retinal neuroinflammation.Retinal ischemia/reperfusion injury was induced in C57BL/6 mice.In a separate cohort of animals,interleukin(IL)-4(50 ng/mL,2μL per injection)or vehicle was intravitreally injected after retinal ischemia/reperfusion injury.RGC loss was assessed by counting cells that were positive for the RGC marker RNA binding protein,mRNA processing factor in retinal flat mounts.The expression of classically activated(M1)and alternatively activated(M2)microglial markers were assessed by quantitative reverse transcription-polymerase chain reaction,immunofluorescence,and western blotting.The results showed that progressive RGC loss was accompanied by a continuous decrease in M2 microglia during the late phase of the 28-day period after retinal ischemia/reperfusion injury.IL-4 was undetectable in the retina at all time points,and intravitreal IL-4 administration markedly improved M2 microglial marker expression and ameliorated RGC loss in the late phase post-retinal ischemia/reperfusion injury.In summary,we observed that IL-4 treatment maintained a high number of M2 microglia after RIR and promoted RGC survival.展开更多
A new phenolic compound, 6-(2-acetyl-3,5-dihydroxybenzyl)-4-hydroxy-3-methyl-2H-pyran-2-one(1), along with other six known phenolic derivatives(2-7), were isolated from the mangrove rhizosphere fungus Penicillium jant...A new phenolic compound, 6-(2-acetyl-3,5-dihydroxybenzyl)-4-hydroxy-3-methyl-2H-pyran-2-one(1), along with other six known phenolic derivatives(2-7), were isolated from the mangrove rhizosphere fungus Penicillium janthinellum HK1-6 cultured in potato dextrose broth medium containing 30 g L^(-1) of natural sea salt. The structure of the new compound(1) was elucidated by comprehensive analysis of spectroscopic data including 1D and 2D NMR spectra. The proposed biosynthetic pathway of compound 1 was also studied in this research. Interestingly, a brominated phenolic derivative, aryl bromide(compound 8), was obtained from this fungal strain cultured in medium containing 30 g L^-1 of NaBr instead of natural sea salt. Compound 8 is proposed as a new natural product and formed through bromination of compound 7 when the fungus was cultured with NaBr. The neuroprotective effect of compound 1 on oxygen-glucose deprivation(OGD)-induced injury was investigated in rat spinal cord astrocytes. MTT assay demonstrated that compound 1 can attenuate OGD-induced cell viability loss in rat spinal cord astrocytes.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
Objective:To determine the chemical structure of the new compound and investigate the protective effects of Tinosporaic acid A and B towards in-vitro neuro.Methods:The structures of two new compounds were established ...Objective:To determine the chemical structure of the new compound and investigate the protective effects of Tinosporaic acid A and B towards in-vitro neuro.Methods:The structures of two new compounds were established by analyzing its 1D and 2D NMR spectra as well as HRESIMS.Their neuroprotective effects with respect to the antioxidant properties were evaluated by radical scavenging tests and hydrogen peroxide-injured oxidative stress model in PC12 cell lines.Cell morphology of treated PC12 cells was observed by phase contrast microscopy.In-vitro MTT assay,lactate dehydrogenase activity assay and oxidative stress markers(intracellular ROS production,MDA level,and caspase-3 activity) were used to evaluate the protective effects against hydrogen peroxide induced cytotoxicity in PC12 cells.Results:The two new compounds,named Tinosporaic acid A and B,were isolated and identified from the stem bark of Tinospora hainanensis.Cell viability studies identified a representative concentration for each extract that was subsequently used to measure oxidative stress markers.Both extracts were able to reverse the oxidative damage caused by hydrogen peroxide,thus promoting PC12 cells survival.The concentration of Tinosporaic acid A and B were 86.34 μg/mL and 22.06 μg/mL respectively,which is neuroprotective for EC_(50).The results indicated that both of them significantly attenuated hydrogen peroxide-induced neurotoxicity.Conclusion:The two new compounds isolated from ethanol extracts of Tinospora hainanensis are the promising natural ones with neuroprotective activity and needed for further research.展开更多
The expected growth of the elderly population at highest risk for Parkinson’s disease(PD)in the next decades makes the identification of factors that promote or prevent the disease an important goal.In addition,new t...The expected growth of the elderly population at highest risk for Parkinson’s disease(PD)in the next decades makes the identification of factors that promote or prevent the disease an important goal.In addition,new therapies-aiming to delay the progression of PD are also needed(Prediger,2010).However,there have been few clinical trials designed to investigate neuroprotection.Thus the application of an appropriate in vitro model such as the neuroblastoma SH-SY5Y cell line is extremely helpful.These cells were selected due to its human origin,catecholaminergic neuronal properties,and ease of maintenance(Xicoy et al.,2017).展开更多
Polysaccharides are macromolecular complexes that have various biological activities.In vivo and in vitro studies have shown that polysaccharides play neuroprotective roles through multiple mechanisms;consequently,the...Polysaccharides are macromolecular complexes that have various biological activities.In vivo and in vitro studies have shown that polysaccharides play neuroprotective roles through multiple mechanisms;consequently,they have potential in the prevention and treatment of neurodegenerative diseases.This paper summarizes related research published during 2015-2020 and reviews advances in the understanding of the neuroprotective effects of bioactive polysaccharides.This review focuses on 15 bioactive polysaccharides from plants and fungi that have neuroprotective properties against oxidative stress,apoptosis,neuroinflammation,and excitatory amino acid toxicity mainly through the regulation of nuclear factor kappa-B,phosphatidylinositol-3-kinase/protein kinase B,mitogen-activated protein kinase,nuclear factor-E2-related factor 2/hemeoxygenase-1,c-jun N-terminal kinase,protein kinase B-mammalian target of rapamycin,and reactive oxygen species-nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain-containing 3 signaling pathways.Natural bioactive polysaccharides have potential in the prevention and treatment of neurodegenerative diseases because of their advantageous characteristics,including multi-targeting,low toxicity,and synergistic effects.However,most of the recent related research has focused on cell and animal models.Future randomized clinical trials involving large sample sizes are needed to validate the therapeutic benefits of these neuroprotective polysaccharides in patients having neurodegenerative diseases.展开更多
Neurodegenerative diseases are a heterogeneous group of disorders characterized by a progressive dysfunction and death of neural cells which lead to compromised motor or cognitive function.Morphologically,the loss of ...Neurodegenerative diseases are a heterogeneous group of disorders characterized by a progressive dysfunction and death of neural cells which lead to compromised motor or cognitive function.Morphologically,the loss of neuron is associated with both gliosis and,frequently,with abnormal accumulation of extracellular and intracellular filamentous deposit in specific cell types.With a rapidly increasing aging population,these diseases are becoming a primary health problem(Albers and Beal,2000).展开更多
Nature is the best source of complementary and alternative medicine. The plant Phyllanthus acidus (PA) L. has been used traditionally in pain, inflammatory and oxidative stress related disorders. In this consequence, ...Nature is the best source of complementary and alternative medicine. The plant Phyllanthus acidus (PA) L. has been used traditionally in pain, inflammatory and oxidative stress related disorders. In this consequence, methanolic extract of PA (MEPA) was selected to explore the ability of this plant to enhance cognitive function, brain antioxidant enzymes and anti-acetylcholinesterase activity which can be used for the treatment of oxidative stress related disorders like Alzheimer’s disease (AD). The purpose of this study was to investigate the neuroprotective effect of MEPA on learning and memory impairment in scopolamine-induced rats of dementia and oxidative stress. Treatment with MEPA (i.e., 100 and 200 mg/kg b.w.) was investigated in scopolamine-treated Swiss albino male rats for 14 days and its neuroprotective effects were examined using Elevated Plus Maze (EPM) test, Passive Avoidance (PA) test, Novel Object Recognition (NOR) test, Morris Water Maze (MWM) test as well as level of antioxidant enzymes such as catalase (CAT), super oxide dismutase (SOD), glutathione reductase (GSR), glutathione-S-transferase (GST), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), lipid peroxidation (TBARS) contents and acetylcholinesterase (AChE) activity in rat brain tissue homogenates. Administration of MEPA significantly (P < 0.05, P < 0.01;P < 0.01) decreased RTL (retention transfer latency) in rats on 7<sup>th</sup> and 14<sup>th</sup> day compared to the disease control and control group in the EPM test. In PA test the doses of MEPA suggestively (P < 0.05, P < 0.001;P < 0.05, P < 0.01) increased STL (step-through latency) in rats on 7<sup>th</sup> and 14<sup>th</sup> day with respect to disease control and control group. For NOR test administration of MEPA considerably (P < 0.01, P < 0.001;P < 0.01) increased the DI (discrimination index) in rats with respect to that of disease control and control group. The doses of MEPA markedly (P < 0.05, P < 0.01;P < 0.01) decreased EL (escape latency) and significantly (P < 0.01, P < 0.001;P < 0.05, P < 0.01) increased TSTQ (time spent in the target quadrant) on successive days as compared to that of disease control and control group in the acquisition trial of MWM test. In case of probe trial of MWM test MEPA administration considerably (P < 0.01;P < 0.05, P < 0.01) increased TSTQ and significantly (P < 0.05, P < 0.01;P < 0.05, P < 0.01) increased TSA (time spent in the annuli) in rats on successive days as compared to that of disease control and control group. MEPA administration significantly (P < 0.05, P < 0.01, P < 0.001;P < 0.05, P < 0.01) increased the level of CAT, SOD, GSR, GST GSH, GSH-Px and markedly (P < 0.01;P < 0.01, P < 0.001) decreased TBARS level through inhibiting lipid peroxidation as well as significantly (P < 0.01, P < 0.001;P < 0.05, P < 0.01, P < 0.001) decreasing AChE activity in rats brain compared to the disease control and control group. The present study demonstrates that MEPA showed the neuroprotective effect by improving cognitive functions and reduces oxidative stress by increasing the level of brain antioxidant enzymes as well as decreasing lipid peroxidation and acetylcholinesterase activity. Therefore, this plant extract can be used for enhancing learning, memory, antioxidant potentiality and anti-acetylcholinesterase activity in neurodegenerative disorders like AD.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
Epidemiologic studies often consider gender differences in a particular pathology,and constantly observe variations between men and women.Indeed,a remarkable sexual dimorphism exists in the epidemiology of neurologica...Epidemiologic studies often consider gender differences in a particular pathology,and constantly observe variations between men and women.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展开更多
Alkaloids are a class of natural products with a wide range of biological activities. Due to the special living environment, the alkaloids from marine sponges have exhibited different biological activities and promisi...Alkaloids are a class of natural products with a wide range of biological activities. Due to the special living environment, the alkaloids from marine sponges have exhibited different biological activities and promising medical application potential. Neolamellarin A is a marine alkaloid possessing bisaryl-pyrrole structural features. Here, the synthesis of 12 different 3,4-bisaryl-N-alkylated permethylated analogues of neolamellarin A and their outstanding neuroprotective activity in PC12 cells are presented and discussed.展开更多
Retinal degeneration is a debilitating ocular complication characterized by the progressive loss of photoreceptors and other retinal neurons,which are caused by a group of retinal diseases affecting various age groups...Retinal degeneration is a debilitating ocular complication characterized by the progressive loss of photoreceptors and other retinal neurons,which are caused by a group of retinal diseases affecting various age groups,and increasingly prevalent in the elderly.Age-related macular degeneration,diabetic retinopathy and glaucoma are among the most common complex degenerative retinal disorders,posing significant public health problems worldwide largely due to the aging society and the lack of effective therapeutics.Whilst pathoetiologies vary,if left untreated,loss of retinal neurons can result in an acquired degeneration and ultimately severe visual impairment.Irrespective of underlined etiology,loss of neurons and supporting cells including retinal pigment epithelium,microvascular endothelium,and glia,converges as the common endpoint of retinal degeneration and therefore discovery or repurposing of therapies to protect retinal neurons directly or indirectly are under intensive investigation.This review overviews recent developments of potential neuroprotectants including neuropeptides,exosomes,mitochondrial-derived peptides,complement inhibitors,senolytics,autophagy enhancers and antioxidants either still experimentally or in clinical trials.Effective treatments that possess direct or indirect neuroprotective properties would significantly lift the burden of visual handicap.展开更多
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DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-butylphthalide action by various means.We used hydrogen peroxide to induce injury to PC12cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of DI-3-n-butylphthalide.We found that DI-3-nbutylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis.Furthermore,DI-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3.DI-3-nbutylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α,the key transcription factor that regulates Bax and Bnip3 genes.These findings suggest that DI-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.
基金supported by MINECO and FEDER funds:ref CPP2021-008855 and RTC-2015-4094-1,Junta de Castilla y León ref.LE025P1 7Neural Therapies SLref.NTDev-01 (all to AFL and JMGO)。
文摘The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects.In this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic inflammation.This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area.We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia.Moreover,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal sprouting.However,this treatment decreased the formation of neuronal progenitor cells.This study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.
基金supported by the National Natural Science Foundation of China,No.81570844the Natural Science Foundation of Fujian Province,No.2011D001+2 种基金Medical Innovation Program of Fujian Province,No.2011-CXB-47Huaxia Translational Medicine Youth Foundation,No.2017-A-00301Xiamen Science and Technology Program Guiding Project,No.3502Z20189033(all to RYW)。
文摘Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors,and which may be mediated by extracellular vesicles(or exosomes)released by mesenchymal stem cells.To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma,we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma.One week after injury,extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity.We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage,increased the number of retinal ganglion cells,and inhibited the activation of caspase-3.These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension,and this effect is achieved by inhibiting cell apoptosis.
基金supported by the Ministry of Higher Education,Government of Malaysia,No.FRGS/2/2014/SG03/UITM/02/2 UiTM IRMI file No.600-RMI/FRGS 5/3(111/2014),toⅡYayasan Penyelidikan Otak,Minda dan Neurosains Malaysia(YPOMNM),No.YPOMNM/2019-04(2)UiTM IRMI No.100-IRMI/PRI 16/6/2(010/2019),to MAML。
文摘Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.
基金supported by the National Natural Science Foundation of China,No.81973501the Natural Science Foundation of Shandong Province,No.ZR2019MH009(both to YLG).
文摘Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations.In addition,the survival,differentiation,and proliferation rates of transplanted exogenous NSCs are low,which limit their clinical application.Our previous study showed that neuregulin1β(NRG1β)alleviated cerebral I/R injury in rats.In this study,we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1βon PC12 cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R).Our results found that 5 and 10 nM NRG1βpromoted the generation and proliferation of NSCs.Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1βimproved the level of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,nicotinamide adenine dinucleotide phosphate,and nuclear factor erythroid 2-related factor 2(Nrf2)and mitochondrial damage in injured PC12 cells;these indexes are related to ferroptosis.Research has reported that p53 and solute carrier family 7 member 11(SLC7A11)play vital roles in ferroptosis caused by cerebral I/R injury.Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4(GPX4)was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells,but this change was alleviated after co-culturing NSCs with damaged PC12 cells.These findings suggest that NSCs pretreated with NRG1βexhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.
基金This investigator-initiated study grant(to SLG)was funded by Novartis,Australiathe funding support from the National Health and Medical Research Council(NHMRC)of Australia,Perpetual Hilcrest,Ophthalmic Research Institute of Australia(ORIA)Macquarie University,NSW,Australia。
文摘Sphingosine-1-phosphate receptor(S1PR)signaling regulates diverse pathophysiological processes in the central nervous system.The role of S1PR signaling in neurodegenerative conditions is still largely unidentified.Siponimod is a specific modulator of S1P1 and S1P5 receptors,an immunosuppressant drug for managing secondary progressive multiple sclerosis.We investigated its neuroprotective properties in vivo on the retina and the brain in an optic nerve injury model induced by a chronic increase in intraocular pressure or acute N-methyl-D-aspartate excitotoxicity.Neuronal-specific deletion of sphingosine-1-phosphate receptor(S1PR1)was carried out by expressing AAV-PHP.eB-Cre recombinase under Syn1 promoter in S1PR1mice to define the role of S1PR1 in neurons.Inner retinal electrophysiological responses,along with histological and immunofluorescence analysis of the retina and optic nerve tissues,indicated significant neuroprotective effects of siponimod when administered orally via diet in chronic and acute optic nerve injury models.Further,siponimod treatment showed significant protection against trans-neuronal degenerative changes in the higher visual center of the brain induced by optic nerve injury.Siponimod treatment also reduced microglial activation and reactive gliosis along the visual pathway.Our results showed that siponimod markedly upregulated neuroprotective Akt and Erk1/2 activation in the retina and the brain.Neuronal-specific deletion of S1PR1 enhanced retinal and dorsolateral geniculate nucleus degenerative changes in a chronic optic nerve injury condition and attenuated protective effects of siponimod.In summary,our data demonstrated that S1PR1signaling plays a vital role in the retinal ganglion cell and dorsolateral geniculate nucleus neuronal survival in experimental glaucoma,and siponimod exerts direct neuroprotective effects through S1PR1 in neurons in the central nervous system independent of its peripheral immuno-modulatory effects.Our findings suggest that neuronal S1PR1 is a neuroprotective therapeutic target and its modulation by siponimod has positive implications in glaucoma conditions.
基金supported by the National Natural Science Foundation of China,Nos. 81873742 (to KFK), 81901195 (to JBS)Nantong Technology Project,Nos. JC2020052 (to XSG),JCZ19087 (to XSG)。
文摘Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.
基金supported by the National Natural Science Foundation of China, No.81970796(to WYG)Clinical Research Program of the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No.JYLJ201905(to WYG)Interdisciplinary Program of Shanghai Jiao Tong University, No.YG2019QNA18(to YW)
文摘Glaucoma results from irreversible loss of retinal ganglion cells(RGCs)through an unclear mechanism.Microglial polarization and neuroinflammation play an important role in retinal degeneration.Our study aimed to explore the function of microglial polarization during glaucoma progression and identify a strategy to alleviate retinal neuroinflammation.Retinal ischemia/reperfusion injury was induced in C57BL/6 mice.In a separate cohort of animals,interleukin(IL)-4(50 ng/mL,2μL per injection)or vehicle was intravitreally injected after retinal ischemia/reperfusion injury.RGC loss was assessed by counting cells that were positive for the RGC marker RNA binding protein,mRNA processing factor in retinal flat mounts.The expression of classically activated(M1)and alternatively activated(M2)microglial markers were assessed by quantitative reverse transcription-polymerase chain reaction,immunofluorescence,and western blotting.The results showed that progressive RGC loss was accompanied by a continuous decrease in M2 microglia during the late phase of the 28-day period after retinal ischemia/reperfusion injury.IL-4 was undetectable in the retina at all time points,and intravitreal IL-4 administration markedly improved M2 microglial marker expression and ameliorated RGC loss in the late phase post-retinal ischemia/reperfusion injury.In summary,we observed that IL-4 treatment maintained a high number of M2 microglia after RIR and promoted RGC survival.
基金supported by the National Natural Science Foundation of China (Nos.81703411, 41830535, U1606403)the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology (Qingdao) (No.2018SD KJ0406-5)+3 种基金the National Science and Technology Major Project for Significant New Drugs Development (No.2018 ZX09735-004)the Program of Open Studio for Druggability Research of Marine Natural Productthe Pilot National Laboratory for Marine Science and Technology (Qingdao, China)Taishan Scholars Program, China。
文摘A new phenolic compound, 6-(2-acetyl-3,5-dihydroxybenzyl)-4-hydroxy-3-methyl-2H-pyran-2-one(1), along with other six known phenolic derivatives(2-7), were isolated from the mangrove rhizosphere fungus Penicillium janthinellum HK1-6 cultured in potato dextrose broth medium containing 30 g L^(-1) of natural sea salt. The structure of the new compound(1) was elucidated by comprehensive analysis of spectroscopic data including 1D and 2D NMR spectra. The proposed biosynthetic pathway of compound 1 was also studied in this research. Interestingly, a brominated phenolic derivative, aryl bromide(compound 8), was obtained from this fungal strain cultured in medium containing 30 g L^-1 of NaBr instead of natural sea salt. Compound 8 is proposed as a new natural product and formed through bromination of compound 7 when the fungus was cultured with NaBr. The neuroprotective effect of compound 1 on oxygen-glucose deprivation(OGD)-induced injury was investigated in rat spinal cord astrocytes. MTT assay demonstrated that compound 1 can attenuate OGD-induced cell viability loss in rat spinal cord astrocytes.
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supported by grants of Hainan provincial project of modernization in traditional Chinese medicine(ZY201426)the Key Science and Technology Program of Hainan Province(ZDXM2014070)the National Natural Science Foundation of China(81460550)
文摘Objective:To determine the chemical structure of the new compound and investigate the protective effects of Tinosporaic acid A and B towards in-vitro neuro.Methods:The structures of two new compounds were established by analyzing its 1D and 2D NMR spectra as well as HRESIMS.Their neuroprotective effects with respect to the antioxidant properties were evaluated by radical scavenging tests and hydrogen peroxide-injured oxidative stress model in PC12 cell lines.Cell morphology of treated PC12 cells was observed by phase contrast microscopy.In-vitro MTT assay,lactate dehydrogenase activity assay and oxidative stress markers(intracellular ROS production,MDA level,and caspase-3 activity) were used to evaluate the protective effects against hydrogen peroxide induced cytotoxicity in PC12 cells.Results:The two new compounds,named Tinosporaic acid A and B,were isolated and identified from the stem bark of Tinospora hainanensis.Cell viability studies identified a representative concentration for each extract that was subsequently used to measure oxidative stress markers.Both extracts were able to reverse the oxidative damage caused by hydrogen peroxide,thus promoting PC12 cells survival.The concentration of Tinosporaic acid A and B were 86.34 μg/mL and 22.06 μg/mL respectively,which is neuroprotective for EC_(50).The results indicated that both of them significantly attenuated hydrogen peroxide-induced neurotoxicity.Conclusion:The two new compounds isolated from ethanol extracts of Tinospora hainanensis are the promising natural ones with neuroprotective activity and needed for further research.
文摘The expected growth of the elderly population at highest risk for Parkinson’s disease(PD)in the next decades makes the identification of factors that promote or prevent the disease an important goal.In addition,new therapies-aiming to delay the progression of PD are also needed(Prediger,2010).However,there have been few clinical trials designed to investigate neuroprotection.Thus the application of an appropriate in vitro model such as the neuroblastoma SH-SY5Y cell line is extremely helpful.These cells were selected due to its human origin,catecholaminergic neuronal properties,and ease of maintenance(Xicoy et al.,2017).
基金supported by the Key Research and Development Support Project of Chengdu Science and Technology Bureau,No.2019-YF05-00655-SN(to WDL)the Key Project of the Medical Science Department,University of Electronic Science and Technology of China,No.ZYGX2020ZB035(to WDL).
文摘Polysaccharides are macromolecular complexes that have various biological activities.In vivo and in vitro studies have shown that polysaccharides play neuroprotective roles through multiple mechanisms;consequently,they have potential in the prevention and treatment of neurodegenerative diseases.This paper summarizes related research published during 2015-2020 and reviews advances in the understanding of the neuroprotective effects of bioactive polysaccharides.This review focuses on 15 bioactive polysaccharides from plants and fungi that have neuroprotective properties against oxidative stress,apoptosis,neuroinflammation,and excitatory amino acid toxicity mainly through the regulation of nuclear factor kappa-B,phosphatidylinositol-3-kinase/protein kinase B,mitogen-activated protein kinase,nuclear factor-E2-related factor 2/hemeoxygenase-1,c-jun N-terminal kinase,protein kinase B-mammalian target of rapamycin,and reactive oxygen species-nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain-containing 3 signaling pathways.Natural bioactive polysaccharides have potential in the prevention and treatment of neurodegenerative diseases because of their advantageous characteristics,including multi-targeting,low toxicity,and synergistic effects.However,most of the recent related research has focused on cell and animal models.Future randomized clinical trials involving large sample sizes are needed to validate the therapeutic benefits of these neuroprotective polysaccharides in patients having neurodegenerative diseases.
基金supported by MIUR-PRIN 2015(N.20152HKF3Z)(to SH)
文摘Neurodegenerative diseases are a heterogeneous group of disorders characterized by a progressive dysfunction and death of neural cells which lead to compromised motor or cognitive function.Morphologically,the loss of neuron is associated with both gliosis and,frequently,with abnormal accumulation of extracellular and intracellular filamentous deposit in specific cell types.With a rapidly increasing aging population,these diseases are becoming a primary health problem(Albers and Beal,2000).
文摘Nature is the best source of complementary and alternative medicine. The plant Phyllanthus acidus (PA) L. has been used traditionally in pain, inflammatory and oxidative stress related disorders. In this consequence, methanolic extract of PA (MEPA) was selected to explore the ability of this plant to enhance cognitive function, brain antioxidant enzymes and anti-acetylcholinesterase activity which can be used for the treatment of oxidative stress related disorders like Alzheimer’s disease (AD). The purpose of this study was to investigate the neuroprotective effect of MEPA on learning and memory impairment in scopolamine-induced rats of dementia and oxidative stress. Treatment with MEPA (i.e., 100 and 200 mg/kg b.w.) was investigated in scopolamine-treated Swiss albino male rats for 14 days and its neuroprotective effects were examined using Elevated Plus Maze (EPM) test, Passive Avoidance (PA) test, Novel Object Recognition (NOR) test, Morris Water Maze (MWM) test as well as level of antioxidant enzymes such as catalase (CAT), super oxide dismutase (SOD), glutathione reductase (GSR), glutathione-S-transferase (GST), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), lipid peroxidation (TBARS) contents and acetylcholinesterase (AChE) activity in rat brain tissue homogenates. Administration of MEPA significantly (P < 0.05, P < 0.01;P < 0.01) decreased RTL (retention transfer latency) in rats on 7<sup>th</sup> and 14<sup>th</sup> day compared to the disease control and control group in the EPM test. In PA test the doses of MEPA suggestively (P < 0.05, P < 0.001;P < 0.05, P < 0.01) increased STL (step-through latency) in rats on 7<sup>th</sup> and 14<sup>th</sup> day with respect to disease control and control group. For NOR test administration of MEPA considerably (P < 0.01, P < 0.001;P < 0.01) increased the DI (discrimination index) in rats with respect to that of disease control and control group. The doses of MEPA markedly (P < 0.05, P < 0.01;P < 0.01) decreased EL (escape latency) and significantly (P < 0.01, P < 0.001;P < 0.05, P < 0.01) increased TSTQ (time spent in the target quadrant) on successive days as compared to that of disease control and control group in the acquisition trial of MWM test. In case of probe trial of MWM test MEPA administration considerably (P < 0.01;P < 0.05, P < 0.01) increased TSTQ and significantly (P < 0.05, P < 0.01;P < 0.05, P < 0.01) increased TSA (time spent in the annuli) in rats on successive days as compared to that of disease control and control group. MEPA administration significantly (P < 0.05, P < 0.01, P < 0.001;P < 0.05, P < 0.01) increased the level of CAT, SOD, GSR, GST GSH, GSH-Px and markedly (P < 0.01;P < 0.01, P < 0.001) decreased TBARS level through inhibiting lipid peroxidation as well as significantly (P < 0.01, P < 0.001;P < 0.05, P < 0.01, P < 0.001) decreasing AChE activity in rats brain compared to the disease control and control group. The present study demonstrates that MEPA showed the neuroprotective effect by improving cognitive functions and reduces oxidative stress by increasing the level of brain antioxidant enzymes as well as decreasing lipid peroxidation and acetylcholinesterase activity. Therefore, this plant extract can be used for enhancing learning, memory, antioxidant potentiality and anti-acetylcholinesterase activity in neurodegenerative disorders like AD.
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.
文摘Epidemiologic studies often consider gender differences in a particular pathology,and constantly observe variations between men and women.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
基金supported by the National Natural Science Foundation of China(Nos.21171154 and 81672585)the Key Technology Fund of Shandong Province(No.2016ZDJS07 A07)the Taishan Scholar Fellowship of Shandong Province in China to L.Z
文摘Alkaloids are a class of natural products with a wide range of biological activities. Due to the special living environment, the alkaloids from marine sponges have exhibited different biological activities and promising medical application potential. Neolamellarin A is a marine alkaloid possessing bisaryl-pyrrole structural features. Here, the synthesis of 12 different 3,4-bisaryl-N-alkylated permethylated analogues of neolamellarin A and their outstanding neuroprotective activity in PC12 cells are presented and discussed.
文摘Retinal degeneration is a debilitating ocular complication characterized by the progressive loss of photoreceptors and other retinal neurons,which are caused by a group of retinal diseases affecting various age groups,and increasingly prevalent in the elderly.Age-related macular degeneration,diabetic retinopathy and glaucoma are among the most common complex degenerative retinal disorders,posing significant public health problems worldwide largely due to the aging society and the lack of effective therapeutics.Whilst pathoetiologies vary,if left untreated,loss of retinal neurons can result in an acquired degeneration and ultimately severe visual impairment.Irrespective of underlined etiology,loss of neurons and supporting cells including retinal pigment epithelium,microvascular endothelium,and glia,converges as the common endpoint of retinal degeneration and therefore discovery or repurposing of therapies to protect retinal neurons directly or indirectly are under intensive investigation.This review overviews recent developments of potential neuroprotectants including neuropeptides,exosomes,mitochondrial-derived peptides,complement inhibitors,senolytics,autophagy enhancers and antioxidants either still experimentally or in clinical trials.Effective treatments that possess direct or indirect neuroprotective properties would significantly lift the burden of visual handicap.
