Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen...Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular rec...The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.展开更多
Hypoxic-ischemic encephalopathy(HIE)is a prominent cause of neuronal damage and neonatal death,and effective treatment strategies remain limited.In a prior investigation,we purified a novel peptide(designated MIP-15)f...Hypoxic-ischemic encephalopathy(HIE)is a prominent cause of neuronal damage and neonatal death,and effective treatment strategies remain limited.In a prior investigation,we purified a novel peptide(designated MIP-15)from the rare mushroom Morchella importuna,demonstrating its notable free radical scavenging activity.Nevertheless,the potential neuroprotective role of MIP-15 in neonatal hypoxic-ischemic brain damage(HIBD)and its underlying mechanism remain elusive.The purpose of this study was to evaluate whether MIP-15 exerts neuroprotective effects by inhibiting the mitochondrial apoptotic pathway after HIBD.A HIBD model in 7-day-old(P7)rats was established by the Rice-Vannucci method to evaluate the effect of MIP-15 on the neurological damage severity and space cognitive ability of rats.Subsequently,an oxygen glucose deprivation/reoxygenation(OGD/R)model was established in rat primary hippocampal neurons to explore the mechanism of MIP-15 action.Both in vivo and in vitro data showed that MIP-15 markedly restored endogenous antioxidative activity,decreased brain water content,and ameliorated pathological abnormalities following HIBD.The spatial cognitive ability and motor function of HIBD rats were also repaired.Moreover,in primary hippocampal neurons after OGD/R,MIP-15 increased cell viability by inhibiting the mitochondrial-dependent apoptosis pathway,as manifested by stabilization of the mitochondrial membrane potential,prevention of the release of cytochrome c,upregulation of Bcl-2/Bax,and reduction in the triggering of caspase proteins.These data indicate that MIP-15 may have the potential to act as a neuroprotective agent.展开更多
The Editor-in-Chief has retracted this article.Following this publication,concerns were raised regarding the similarity of images presented in this article with previously published articles[1,2].The authors were unab...The Editor-in-Chief has retracted this article.Following this publication,concerns were raised regarding the similarity of images presented in this article with previously published articles[1,2].The authors were unable to provide a satisfactory explanation and raw data for the concerns upon request.展开更多
Eight previously undescribed lanostane triterpenoids,including five nortriterpenoids with 26carbons,ganothenoids A-E(1-5),and three lanostanoids,ganothenoids F-H(6-8),along with 24 known ones(9-32),were isolated from ...Eight previously undescribed lanostane triterpenoids,including five nortriterpenoids with 26carbons,ganothenoids A-E(1-5),and three lanostanoids,ganothenoids F-H(6-8),along with 24 known ones(9-32),were isolated from the fruiting bodies of Ganodrma theaecolum.The structures of the novel compounds were elucidated using comprehensive spectroscopic methods,including electronic circular dichroism(ECD)and nuclear magnetic resonance(NMR)calculations.Compounds 1-32 were assessed for their neuroprotective effects against H_(2)O_(2)-induced damage in human neuroblastoma SH-SY5Y cells,as well as their inhibitory activities against protein tyrosine phosphatase 1B(PTP1B)andα-glucosidase.Compound 4demonstrated the most potent neuroprotective activity against H_(2)O_(2)-induced oxidative stress by suppressing G_0/G_1 phase cell cycle arrest,reducing reactive oxygen species(ROS)levels,and inhibiting cell apoptosis through modulation of B-cell lymphoma 2 protein(Bcl-2)and Bcl-2 associated X-protein(Bax)protein expression.Compounds 26,12,and 28 exhibited PTP1B inhibitory activities with IC_(50)values ranging from 13.92 to 56.94μmol·L~(-1),while compound12 alone displayed significant inhibitory effects onα-glucosidase with an IC_(50)value of 43.56μmol·L~(-1).Additionally,enzyme kinetic analyses and molecular docking simulations were conducted for compounds 26 and 12 with PTP1B andα-glucosidase,respectively.展开更多
Alzheimer’s disease(AD)is a progressive neurodegenerative condition characterized by memory loss and cognitive decline.Current drugs offer limited benefits and often cause side effects.Recently,interest has grown in ...Alzheimer’s disease(AD)is a progressive neurodegenerative condition characterized by memory loss and cognitive decline.Current drugs offer limited benefits and often cause side effects.Recently,interest has grown in medicinal plants for the treatment of AD due to their neuroprotective compounds.This review explores how herbal remedies may help AD,focus-ing on key plants including Ginkgo biloba,Curcuma longa,Withania somnifera,and Panax ginseng.These plants show promise in reducing inflammation,oxidative stress,and amyloid buildup.Their bioactive compounds,including flavonoids and alkaloids,may promote mem-ory and slow AD progression.Despite these promising findings,the review also highlights sig-nificant challenges in translating preclinical success into clinical efficacy.Issues such as vari-ability in plant composition,lack of standardized formulations,insufficient large-scale clini-cal trials,and regulatory hurdles continue to impede the integration of herbal therapies into mainstream AD treatment.Addressing these challenges through rigorous scientific validation and standardized protocols is essential for advancing the use of herbal medicine in neurode-generative disease management.展开更多
Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Curre...Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.展开更多
Magnesium(Mg)alloy stents have been commercialized for the treatment of cardiovascular diseases and extensively studied for possible implantation in major organs.However,the in vivo studies regarding the neuroactivity...Magnesium(Mg)alloy stents have been commercialized for the treatment of cardiovascular diseases and extensively studied for possible implantation in major organs.However,the in vivo studies regarding the neuroactivity of Mg alloys extracts are few.Therefore,the safety and neuroprotective effects of released degradation products(Mg^(2+)and H_(2))from Mg alloys on ischemic brain tissues were investigated.To be specific,C57BL/6 mice with middle cerebral artery occlusion(MCAO)were injected intraperitoneally of saline,pure Mg extracts,WE43 extracts and hydrogen(H_(2))-removed WE43 Mg alloy extracts(75 mL/kg)respectively immediately after reperfusion.The neurobehavioral assessment stated clearly that WE43 extracts could remarkably recover the neurological deficits of MCAO mice.We explored the underlying mechanisms and demonstrated that the Mg^(2+)and H_(2)from WE43 extracts could perform anti-inflammatory and anti-oxidative function after MCAO in mice,by increasing the expressions of IL-4,TGF-β1,SOD1 and decreasing the expressions of IL-1β,CXCR2,MDA.Simultaneously,Mg^(2+)and H_(2)contributed to increase cerebral blood flow and restore blood-brain barrier integrity.In conclusion,this study provides certain theoretical representation of the application of Mg alloy stents in intracranial vessels.展开更多
Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the di...Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.展开更多
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
Alzheimer's disease(AD)is the leading cause of dementia,and no effective treatment has been developed for it thus far.Recently,the use of natural compounds in the treatment of neurodegenerative diseases has garner...Alzheimer's disease(AD)is the leading cause of dementia,and no effective treatment has been developed for it thus far.Recently,the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions.Accordingly,the potential therapeutic effect of pterostilbene(PTS)on AD has been demonstrated in multiple in vivo and in vitro experiments.In this study,we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD.Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms,including anti-oxidative damage,anti-neuroinflammation,anti-apoptosis,cholinesterase activity inhibition,attenuation ofβ-amyloid deposition,and tau protein hyperphosphorylation.Moreover,PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha(PPAR-α),monoamine oxidase B(MAO-B),silent information regulator sirtuin 1(SIRT1),and phosphodiesterase 4A(PDE4A).Furthermore,to further elucidate the potential therapeutic mechanisms of PTS in AD,we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins,and the obtained binding energies ranged from-2.83 to-5.14 kJ/mol,indicating that these proteins exhibit good binding ability with PTS.Network pharmacology analysis revealed multiple potential mechanisms of action for PTS in AD.In summary,by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD,it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD,either using PTS or other developed drug interventions.展开更多
The increasing incidence of neurodegenerative diseases(NDs)and the constraints of existing treatment methods have spurred a keen interest in investigating alternative therapies.Medicinal plants,renowned for their long...The increasing incidence of neurodegenerative diseases(NDs)and the constraints of existing treatment methods have spurred a keen interest in investigating alternative therapies.Medicinal plants,renowned for their long-standing use in traditional medicine,offer a hopeful avenue for discovering new neuroprotective agents.This study emphasizes the potential neuroprotective characteristics of edible fruit plants in Bangladesh,specifically focusing on their traditional folk medicine uses for neurological disorders.This study provides an in-depth overview of the different types of edible fruit trees in Bangladesh and their phytochemicals,including flavonoids,terpenoids,and phenolic acids.This work examines the scientific data supporting the neuroprotective properties of bioactive chemicals from plants.It further explores the mechanisms by which these compounds work to counteract oxidative stress,decrease inflammation,and stimulate neurogenesis.Moreover,the study investigates toxicological characteristics and bioactive components of some fruits,emphasizing the importance of further investigation to measure their safety profile comprehensively.This thorough study highlights the potential benefits of Bangladesh's edible fruit trees as a rich source of neuroprotective chemicals.It also shows that additional research might lead to novel approaches for improving brain functioning and preventing NDs.展开更多
Unhealthy diets are associated with various diseases that can disrupt brain energy metabolism,which significantly increased the risk of cognitive impairment and chronic neurodegenerative diseases.Early intervention wi...Unhealthy diets are associated with various diseases that can disrupt brain energy metabolism,which significantly increased the risk of cognitive impairment and chronic neurodegenerative diseases.Early intervention with nutritional supplements may have long-lasting positive effects on diet-related glucose metabolism and potentially mediate the progression of neurodegeneration in middle-aged and elderly people.We previously reported that cyanidin 3-O-β-galactoside(Cy3Gal),an anthocyanin from black chokeberry(Aronia melanocarpa(Michx.)Elliott),alleviated cognitive impairment in aging mice through regulating brain energy metabolism.However,it remains unclear whether Cy3Gal can also exert beneficial effects in mice fed with a high-fat/high-sugar diet.Here we revealed that Cy3Gal treatment conserved the health of neurons and synapses,as well as cognitive function of mice.Furthermore,we observed that Cy3Gal effectively improved glucose uptake and metabolism of skeletal muscle by enhancing glycolysis both in vivo and in vitro models,which is essential for maintaining a stable glucose supply to the brain.Additionally,Cy3Gal significantly increased the levels of glucose-derived tricarboxylic acid cycle intermediates in the mice brain(P<0.05),and regulated the activities of mitochondrial respiratory chain complexes(P<0.01).The positive influence on peripheral and brain bioenergetics explained how the Cy3Gal exerted neuroprotective effect.In conclusion,our study illustrated that early dietary intervention of Cy3Gal had significant advantages in terms of neuroprotection and cognition under the challenge of HFHS diet-induced glucose metabolism disorder.展开更多
4-Acylated or 3,4-diacylated caffeic acid phenethyl ester （CAPE） was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H202 model and 6-OHDA model. ...4-Acylated or 3,4-diacylated caffeic acid phenethyl ester （CAPE） was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H202 model and 6-OHDA model. The results showed that target compounds displayed positive abilities to protect PC 12 nerve cells from oxidative stress injury, superior to that of CAPE. Additionally, target compounds showed high blood-brain barrier permeability.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
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
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
A new series of compounds （E）-1-（4-（bis-arylmethyl）piperazin-l-yl）-3-arylprop-2-en-1-one （1a-r）, have been synthesized and their structures were confirmed by ESI-MS and 1H NMR. The preliminary pharmacological ...A new series of compounds （E）-1-（4-（bis-arylmethyl）piperazin-l-yl）-3-arylprop-2-en-1-one （1a-r）, have been synthesized and their structures were confirmed by ESI-MS and 1H NMR. The preliminary pharmacological screening showed that some of these compounds had similar neuroprotective effects with Edaravone.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171387 and 31830111(both to SL).
文摘Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金supported by the National Natural Science Foundation of China,Nos.82301093(to QC)and 22334004(to HY)the Fuzhou University Fund for Testing Precious Equipment,No.2025T038(to QC)。
文摘The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.
基金supported by Natural Science Foundation of Sichuan Province(2022NSFSC0112)the International Communication and Collaboration Project of Sichuan Academy of Agricultural Sciences(2022ZSSFGH09)the Independent Innovation Project of Sichuan Academy of Agricultural Sciences(2022ZZCX028)。
文摘Hypoxic-ischemic encephalopathy(HIE)is a prominent cause of neuronal damage and neonatal death,and effective treatment strategies remain limited.In a prior investigation,we purified a novel peptide(designated MIP-15)from the rare mushroom Morchella importuna,demonstrating its notable free radical scavenging activity.Nevertheless,the potential neuroprotective role of MIP-15 in neonatal hypoxic-ischemic brain damage(HIBD)and its underlying mechanism remain elusive.The purpose of this study was to evaluate whether MIP-15 exerts neuroprotective effects by inhibiting the mitochondrial apoptotic pathway after HIBD.A HIBD model in 7-day-old(P7)rats was established by the Rice-Vannucci method to evaluate the effect of MIP-15 on the neurological damage severity and space cognitive ability of rats.Subsequently,an oxygen glucose deprivation/reoxygenation(OGD/R)model was established in rat primary hippocampal neurons to explore the mechanism of MIP-15 action.Both in vivo and in vitro data showed that MIP-15 markedly restored endogenous antioxidative activity,decreased brain water content,and ameliorated pathological abnormalities following HIBD.The spatial cognitive ability and motor function of HIBD rats were also repaired.Moreover,in primary hippocampal neurons after OGD/R,MIP-15 increased cell viability by inhibiting the mitochondrial-dependent apoptosis pathway,as manifested by stabilization of the mitochondrial membrane potential,prevention of the release of cytochrome c,upregulation of Bcl-2/Bax,and reduction in the triggering of caspase proteins.These data indicate that MIP-15 may have the potential to act as a neuroprotective agent.
文摘The Editor-in-Chief has retracted this article.Following this publication,concerns were raised regarding the similarity of images presented in this article with previously published articles[1,2].The authors were unable to provide a satisfactory explanation and raw data for the concerns upon request.
基金supported by the National Natural Science Foundation of China (No.81973568)the Earmarked Fund for China Agriculture Research System (No.CARS-21)the Special Financial Project of the Ministry of Agriculture and Rural Areas (No.NFZX2024)。
文摘Eight previously undescribed lanostane triterpenoids,including five nortriterpenoids with 26carbons,ganothenoids A-E(1-5),and three lanostanoids,ganothenoids F-H(6-8),along with 24 known ones(9-32),were isolated from the fruiting bodies of Ganodrma theaecolum.The structures of the novel compounds were elucidated using comprehensive spectroscopic methods,including electronic circular dichroism(ECD)and nuclear magnetic resonance(NMR)calculations.Compounds 1-32 were assessed for their neuroprotective effects against H_(2)O_(2)-induced damage in human neuroblastoma SH-SY5Y cells,as well as their inhibitory activities against protein tyrosine phosphatase 1B(PTP1B)andα-glucosidase.Compound 4demonstrated the most potent neuroprotective activity against H_(2)O_(2)-induced oxidative stress by suppressing G_0/G_1 phase cell cycle arrest,reducing reactive oxygen species(ROS)levels,and inhibiting cell apoptosis through modulation of B-cell lymphoma 2 protein(Bcl-2)and Bcl-2 associated X-protein(Bax)protein expression.Compounds 26,12,and 28 exhibited PTP1B inhibitory activities with IC_(50)values ranging from 13.92 to 56.94μmol·L~(-1),while compound12 alone displayed significant inhibitory effects onα-glucosidase with an IC_(50)value of 43.56μmol·L~(-1).Additionally,enzyme kinetic analyses and molecular docking simulations were conducted for compounds 26 and 12 with PTP1B andα-glucosidase,respectively.
文摘Alzheimer’s disease(AD)is a progressive neurodegenerative condition characterized by memory loss and cognitive decline.Current drugs offer limited benefits and often cause side effects.Recently,interest has grown in medicinal plants for the treatment of AD due to their neuroprotective compounds.This review explores how herbal remedies may help AD,focus-ing on key plants including Ginkgo biloba,Curcuma longa,Withania somnifera,and Panax ginseng.These plants show promise in reducing inflammation,oxidative stress,and amyloid buildup.Their bioactive compounds,including flavonoids and alkaloids,may promote mem-ory and slow AD progression.Despite these promising findings,the review also highlights sig-nificant challenges in translating preclinical success into clinical efficacy.Issues such as vari-ability in plant composition,lack of standardized formulations,insufficient large-scale clini-cal trials,and regulatory hurdles continue to impede the integration of herbal therapies into mainstream AD treatment.Addressing these challenges through rigorous scientific validation and standardized protocols is essential for advancing the use of herbal medicine in neurode-generative disease management.
文摘Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.
基金supported by the National Natural Science Foundation of China(82102220 and 82027802)Excellent Youth Fund of Capital Medical University(B2305),Beijing Natural Science Foundation(7244510)+4 种基金Research Funding on Translational Medicine from Beijing Municipal Science and Technology Commission(Z221100007422023)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support from Yangfan Project(YGLX202325)the Non-profit Central Research Institute Fund of Chinese Academy of Medical(2023-JKCS-09)Beijing Association for Science and Technology Youth Talent Support Program(BYESS2022081)Science and Technology Innovation Service Capacity Building Project of Beijing Municipal Education Commission(11000023T000002157177).
文摘Magnesium(Mg)alloy stents have been commercialized for the treatment of cardiovascular diseases and extensively studied for possible implantation in major organs.However,the in vivo studies regarding the neuroactivity of Mg alloys extracts are few.Therefore,the safety and neuroprotective effects of released degradation products(Mg^(2+)and H_(2))from Mg alloys on ischemic brain tissues were investigated.To be specific,C57BL/6 mice with middle cerebral artery occlusion(MCAO)were injected intraperitoneally of saline,pure Mg extracts,WE43 extracts and hydrogen(H_(2))-removed WE43 Mg alloy extracts(75 mL/kg)respectively immediately after reperfusion.The neurobehavioral assessment stated clearly that WE43 extracts could remarkably recover the neurological deficits of MCAO mice.We explored the underlying mechanisms and demonstrated that the Mg^(2+)and H_(2)from WE43 extracts could perform anti-inflammatory and anti-oxidative function after MCAO in mice,by increasing the expressions of IL-4,TGF-β1,SOD1 and decreasing the expressions of IL-1β,CXCR2,MDA.Simultaneously,Mg^(2+)and H_(2)contributed to increase cerebral blood flow and restore blood-brain barrier integrity.In conclusion,this study provides certain theoretical representation of the application of Mg alloy stents in intracranial vessels.
基金supported by Karolinska Institutet in the form of a Board of Research Faculty Funded Career Positionby St.Erik Eye Hospital philanthropic donationsVetenskapsrådet 2022-00799.
文摘Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.
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.
基金supported by the 345 Talent Project[40B]of Shengjing Hospital of China Medical University,Shenyang,China.
文摘Alzheimer's disease(AD)is the leading cause of dementia,and no effective treatment has been developed for it thus far.Recently,the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions.Accordingly,the potential therapeutic effect of pterostilbene(PTS)on AD has been demonstrated in multiple in vivo and in vitro experiments.In this study,we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD.Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms,including anti-oxidative damage,anti-neuroinflammation,anti-apoptosis,cholinesterase activity inhibition,attenuation ofβ-amyloid deposition,and tau protein hyperphosphorylation.Moreover,PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha(PPAR-α),monoamine oxidase B(MAO-B),silent information regulator sirtuin 1(SIRT1),and phosphodiesterase 4A(PDE4A).Furthermore,to further elucidate the potential therapeutic mechanisms of PTS in AD,we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins,and the obtained binding energies ranged from-2.83 to-5.14 kJ/mol,indicating that these proteins exhibit good binding ability with PTS.Network pharmacology analysis revealed multiple potential mechanisms of action for PTS in AD.In summary,by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD,it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD,either using PTS or other developed drug interventions.
文摘The increasing incidence of neurodegenerative diseases(NDs)and the constraints of existing treatment methods have spurred a keen interest in investigating alternative therapies.Medicinal plants,renowned for their long-standing use in traditional medicine,offer a hopeful avenue for discovering new neuroprotective agents.This study emphasizes the potential neuroprotective characteristics of edible fruit plants in Bangladesh,specifically focusing on their traditional folk medicine uses for neurological disorders.This study provides an in-depth overview of the different types of edible fruit trees in Bangladesh and their phytochemicals,including flavonoids,terpenoids,and phenolic acids.This work examines the scientific data supporting the neuroprotective properties of bioactive chemicals from plants.It further explores the mechanisms by which these compounds work to counteract oxidative stress,decrease inflammation,and stimulate neurogenesis.Moreover,the study investigates toxicological characteristics and bioactive components of some fruits,emphasizing the importance of further investigation to measure their safety profile comprehensively.This thorough study highlights the potential benefits of Bangladesh's edible fruit trees as a rich source of neuroprotective chemicals.It also shows that additional research might lead to novel approaches for improving brain functioning and preventing NDs.
基金supported by the National Natural Science Foundation of China(32172210).
文摘Unhealthy diets are associated with various diseases that can disrupt brain energy metabolism,which significantly increased the risk of cognitive impairment and chronic neurodegenerative diseases.Early intervention with nutritional supplements may have long-lasting positive effects on diet-related glucose metabolism and potentially mediate the progression of neurodegeneration in middle-aged and elderly people.We previously reported that cyanidin 3-O-β-galactoside(Cy3Gal),an anthocyanin from black chokeberry(Aronia melanocarpa(Michx.)Elliott),alleviated cognitive impairment in aging mice through regulating brain energy metabolism.However,it remains unclear whether Cy3Gal can also exert beneficial effects in mice fed with a high-fat/high-sugar diet.Here we revealed that Cy3Gal treatment conserved the health of neurons and synapses,as well as cognitive function of mice.Furthermore,we observed that Cy3Gal effectively improved glucose uptake and metabolism of skeletal muscle by enhancing glycolysis both in vivo and in vitro models,which is essential for maintaining a stable glucose supply to the brain.Additionally,Cy3Gal significantly increased the levels of glucose-derived tricarboxylic acid cycle intermediates in the mice brain(P<0.05),and regulated the activities of mitochondrial respiratory chain complexes(P<0.01).The positive influence on peripheral and brain bioenergetics explained how the Cy3Gal exerted neuroprotective effect.In conclusion,our study illustrated that early dietary intervention of Cy3Gal had significant advantages in terms of neuroprotection and cognition under the challenge of HFHS diet-induced glucose metabolism disorder.
基金National Natural Science Foundation of China(Grant No.201310061931.8)
文摘4-Acylated or 3,4-diacylated caffeic acid phenethyl ester （CAPE） was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H202 model and 6-OHDA model. The results showed that target compounds displayed positive abilities to protect PC 12 nerve cells from oxidative stress injury, superior to that of CAPE. Additionally, target compounds showed high blood-brain barrier permeability.
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.
基金the Natural Science Foundation of Education Department of Jiangsu Province(No.05KJB350084).
文摘A new series of compounds （E）-1-（4-（bis-arylmethyl）piperazin-l-yl）-3-arylprop-2-en-1-one （1a-r）, have been synthesized and their structures were confirmed by ESI-MS and 1H NMR. The preliminary pharmacological screening showed that some of these compounds had similar neuroprotective effects with Edaravone.
