Astragalin Ameliorates Cognitive Dysfunction Through Inhibiting PI3K/Akt-MTOR-Mediated Autophagic Flow in Hippocampal Neurons of APP/PS1 Mice

2022 ◽  
Author(s):  
Cuizhu Yang ◽  
Runheng Zhang ◽  
Shuhan Wang ◽  
Yinghong Tian ◽  
Yaqi Yang ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Mtor Signaling Pathway ◽  
Neuroprotective Effects ◽  
Chinese Medicines ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Paeoniae Radix ◽  
Analysis Platform

Abstract Astragalin (AST), a natural small molecule flavonoid, can exert anti-oxidant, anti-inflammatory and anti-cancer impacts by regulating autophagy. However, the potential mechanism of the neuroprotective effect of AST on neurological disorders such as Alzheimer’s disease (AD) is still not clear. In the present study, we firstly screened AST for the treatment of AD from the ingredients of Chinese medicines such as Acori tataninowii Rhizoma, Eucommiae Cortex, Paeoniae Radix Alba through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database. And then we found that AST could improve the cognitive abilities of APP/PS1 mice by Step-down passive avoidance (SDA) and Morris Water Maze (MWM) Test. Further, we identified that AST diminished Aβ plaques deposition in the brains of APP/PS1 mice and Aβ as well as Aβ42 levels in the serum of APP/PS1 mice. Next, microtubule-associated protein 1 light chain 3B (LC3B), p62, Beclin-1, ATG5, ATG12, LAMP-1 were observed to be co-expressed with NeuN in the hippocampus of APP/PS1 mice by immunofluorescent multiplex staining, while AST was able to activate autophagy and maintain autophagic flow in hippocampal neurons of APP/PS1 mice by western blot (WB) analysis. Finally, AST reduced the expressions of p-PI3K, p-Akt, p-mTOR by WB analysis. Taken together, we confirmed that AST may play key neuroprotective effects on APP/PS1 mice by inhibiting the PI3K/Akt-mTOR signaling pathway to activate autophagy and keep autophagic flow smooth.

scholarly journals Neuroprotective Effects of Curcumin-Loaded Emulsomes on Laser Axotomy-Induced CNS Injury Model

2020 ◽  
Author(s):  
Elif Nur Yilmaz ◽  
Sadik Bay ◽  
Gurkan Ozturk ◽  
Mehmet Hikmet Ucisik
Keyword(s):  
Hippocampal Neurons ◽  
Caspase 3 ◽  
Ex Vivo ◽  
Neuroprotective Effect ◽  
Axonal Injury ◽  
Survival Rates ◽  
Cns Injury ◽  
Neuroprotective Effects ◽  
Injury Model ◽  
Apoptotic Marker

Abstract Background Curcumin, a polyphenol isolated from the rhizomes of turmeric, holds a great potential as a neuroprotective agent along with its anti-inflammatory and antioxidant characteristics. Its poor bioavailability and low stability in water lie as foremost restraints against the clinical use. This study aims at investigating the neuroprotective effect of curcumin on axonal injury by delivering the lipophilic polyphenol to primary hippocampal neuron by means of a lipid-based drug delivery system, named emulsomes. Methods To study the neuroregeneration on ex vivo, an injury model was established through single-cell laser axotomy on hippocampal neurites. Upon treatment with curcumin-loaded emulsomes (CurcuEmulsomes), curcumin and CurcuEmulsome uptake into neurons were verified by 3-dimensional z-stack images acquired with confocal microscopy. Neuron survival after axonal injury were tracked by PI and Hoechst staining. Alterations in expression levels of physiological markers such as anti-apoptotic marker Bcl-2, apoptotic marker cleaved caspase 3, neuroprotective marker Wnt3a and the neuronal survival marker mTOR were investigated by immunocytochemistry analyses. Results Results indicated significant improvement in the survival rates of injured neurons upon CurcuEmulsome treatment. Bcl-2 expression became significantly higher for injured neurons treated with curcumin or CurcuEmulsome. Caspase 3 expressions decreased in both curcumin- and CurcuEmulsome-treatments, whereas Wnt3a and mTOR expressions did not alter significantly. Conclusions The established laser-axotomy model was exposed as a reliable methodology to study neurodegenerative models ex vivo. CurcuEmulsomes delivered curcumin to primary hippocampal neurons successfully. Treated with CurcuEmulsomes, injured hippocampal neurons benefit from neuroprotective effects of curcumin in terms of higher survival rate and increased anti-apoptotic marker levels.

scholarly journals Modulation of Preactivation of PPAR-βon Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Ge Kuang ◽  
Qin He ◽  
Yunmei Zhang ◽  
Ruichun Zhuang ◽  
Anling Xiang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Hippocampal Neurons ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Global Cerebral Ischemia ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

The aim of this study is to investigate the neuroprotective effects and relevant mechanism of GW0742, an agonist of PPAR-β, after global cerebral ischemia-reperfusion injury (GCIRI) in rats. The rats showed memory and cognitive impairment and cytomorphological change in the hippocampus neurons following GCIRI. These effects were significantly improved by pretreatment with GW0742 in the dose-dependent manner. The expressions of IL-1β, IL-6, and TNF-αwere increased after GCIRI, while the increases in these proinflammatory cytokines by GCIRI were inhibited by GW0742 pretreatment. Similarly, GW0742 pretreatment also improved the GCIRI-induced decrease in the expression of IL-10, which can act as an inhibitory cytokine to reduce cerebral ischemic injury. For another, NF-κB p65 expression was significantly increased in hippocampal neurons with apparent nuclear translocation after global cerebral IRI, and these phenomena were also largely attenuated by GW0742 pretreatment. Moreover, the mRNA and protein expressions of PPAR-βwere significantly decreased in GCIRI + GW0742 groups when compared with those in GCIRI group. Our data suggests that the PPAR-βagonist GW0742 can exert significant neuroprotective effect against GCIRI in rats via PPAR-βactivation and its anti-inflammation effect mediated by the inhibition of expression and activation of NF-κB in the hippocampus.

scholarly journals Fisetin Regulates Gut Microbiota and Exerts Neuroprotective Effect on Mouse Model of Parkinson’s Disease

2020 ◽  
Vol 14 ◽  
Author(s):  
Tian-Jiao Chen ◽  
Ya Feng ◽  
Te Liu ◽  
Ting-Ting Wu ◽  
Ya-Jing Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Neuroprotective Effect ◽  
Mice Model ◽  
Alpha And Beta Diversity ◽  
Dopaminergic Neurodegeneration ◽  
Anti Cancer ◽  
Fresh Feces ◽  
Anti Oxidant

Previous studies have reported the anti-oxidant, anti-inflammatory, and anti-cancer effects of fisetin. However, the therapeutic efficacy of fisetin in Parkinson’s disease (PD) is unclear. In this study, we demonstrated that fisetin could markedly alleviate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration in mice. To confirm the reported correlation between gut microbiota and PD, the bacterial DNA in the fresh feces of mice from each group was subjected to 16S rRNA (V3 and V4 regions) sequencing. The results revealed that fisetin changed the number, diversity, and distribution of gut microbiota in MPTP-induced mice model of PD. The alpha and beta diversity analyses showed that the fisetin intervented MPTP group gut microbiota exhibited a significantly higher abundance of Lachnospiraceae and a significantly lower abundance of uncultured_bacterium_g_Escherichia-Shigella and uncultured_bacterium_g_Bacillus than the MPTP group gut microbiota. These findings indicated that fisetin exerts a neuroprotective effect on neurodegeneration by altering the composition and diversity of gut microbiota. Thus, fisetin could be a potential novel therapeutic for PD.

scholarly journals Protein Kinase C Involvement in Neuroprotective Effects of Thymol and Carvacrol Against Toxicity Induced by Amyloid-Β in Rat Hippocampal Neurons

2021 ◽  
Author(s):  
Zahra Azizi ◽  
◽  
Samira Choopani ◽  
Mona Salimi ◽  
Nahid Majlessi ◽  
...  
Keyword(s):  
Rat Model ◽  
Cognitive Abilities ◽  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Underlying Mechanism ◽  
Control Group ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Expression Ratio

Introduction: We have reported that thymol and carvacrol can improve cognitive abilities in Alzheimer’s disease (AD) rat model. However, the mechanism of their action is not yet fully understood. Recently, our in vitro results suggested that PC12 cell death-induced by Aβ25-35 can be protected by thymol and carvacrol via PKC and ROS pathways. So, we hypothesize that the mechanisms of thymol and carvacrol in improving the learning impairment in AD rat model may be related to their effects on PKC. So, the activity of PKC and protein expression levels of PKCα was examined in the hippocampal cells of AD rat model. Methods: To examine thymol and carvacrol effects, we performed behavioral test in AD rat model induced by Aβ25–35 neurotoxicity. To access the underlying mechanism of protective effects, western blotting was performed with antibodies against PKCα. We also measured PKC activity assay by Elisa. Histopathological studies were carried out in hippocampus by hematoxylin & eosin (H&E). Results: It was shown that escape latency increased in Aβ-received rats compared to control group and thymol and carvacrol reversed this deficit. Furthermore, these compouds could enhance PKC activity, and increase the PKCα expression ratio. Moreover, H&E showed that Aβ caused shrinkage of the CA1 pyramidal neurons. However, thymol and carvacrol treatments could prevent this effect of Aβ peptides. Conclusions: This study suggests that Aβ results in memory decline and histochemical disturbances in hippocampus. Moreover, these results revealed that thymol and carvacrol could have protective effects on cognition in AD-like models via PKC activation.

scholarly journals Anti-Cancer Activity of Andrographolide: A Review

2021 ◽  
pp. 1-9
Author(s):  
Vishwanadham Yerragunta ◽  
Kavita Waghray ◽  
. Shivraj ◽  
N. J. P. Subhashini
Keyword(s):  
Biological Activities ◽  
Pharmacological Activities ◽  
Neuroprotective Effects ◽  
Cytotoxic Effects ◽  
Research Activities ◽  
Anti Cancer ◽  
Research Findings ◽  
Anti Oxidant ◽  
Anti Inflammation

Andrographolide, is a chemical compound obtained from the Andrographis paniculata (Family- Acanthaceae), maybe a diterpene lactone ring is responsible for various biological activities like anti-inflammation, anti-microbial anti-cancer, anti-obesity, anti-diabetes, anti-oxidant immunomodulatory, antiseptic, hypolipidemic, cardioprotective, hepatoprotective, neuroprotective effects and other biological activities. In Current research activities worldwide to exhibit the beneficial role of Andrographolide are continuously enriching the therapeutic arsenal of this important Phyto molecule. For this purpose, several databases were accustomed explore for the anticancer/cytotoxic effects of the andrographolide in pre-clinical and clinical studies. During this report, an attempt has been given to spotlight the research findings, related to therapeutic potentials and up-to-date development within the pharmacological activities of andrographolide. Andrographolide is often one of the potential agents within the treatment of cancer.

scholarly journals Neuroprotective Effects of Lycium barbarum Berry on Neurobehavioral Changes and Neuronal Loss in the Hippocampus of Mice Exposed to Acute Ionizing Radiation

Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110577
Author(s):  
Lei Guo ◽  
Qian-Qian Du ◽  
Piao-Qin Cheng ◽  
Ting-Ting Yang ◽  
Chao-Qun Xing ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Dentate Gyrus ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Water Extract ◽  
Water Soluble ◽  
Lycium Barbarum ◽  
Neuroprotective Effects ◽  
Neuron Loss ◽  
Radiation Induced

Background: Brain exposure to ionizing radiation during the radiotherapy of brain tumor or metastasis of peripheral cancer cells to the brain has resulted in cognitive dysfunction by reducing neurogenesis in hippocampus. The water extract of Lycium barbarum berry (Lyc), containing water-soluble Lycium barbarum polysaccharides and flavonoids, can protect the neuronal injury by reducing oxidative stress and suppressing neuroinflammation. Reseach Design: To demonstrate the long-term radioprotective effect of Lyc, we evaluated the neurobehavioral alterations and the numbers of NeuN, calbindin (CB), and parvalbumin (PV) immunopositive hippocampal neurons in BALB/c mice after acute 5.5 Gy radiation with/without oral administration of Lyc at the dosage of 10 g/kg daily for 4 weeks. Results: The results showed that Lyc could improve irradiation-induced animal weight loss, depressive behaviors, spatial memory impairment, and hippocampal neuron loss. Immunohistochemistry study demonstrated that the loss of NeuN-immunopositive neuron in the hilus of the dentate gyrus, CB-immunopositive neuron in CA1 strata radiatum, lacunosum moleculare and oriens, and PV-positive neuron in CA1 stratum pyramidum and stratum granulosum of the dentate gyrus after irradiation were significantly improved by Lyc treatment. Conclusion: The neuroprotective effect of Lyc on those hippocampal neurons may benefit the configuration of learning related neuronal networks and then improve radiation induced neurobehavioral changes such as cognitive impairment and depression. It suggests that  Lycium barbarum berry may be an alternative food supplement to prevent radiation-induced neuron loss and neuropsychological disorders.

scholarly journals Neuroprotective Effects of Lycium Barbarum Berry on Neurobehavioral Changes and Neuronal Loss in the Hippocampus of Mice Exposed to Acute Ionizing Radiation

2021 ◽  
Author(s):  
Lei Guo ◽  
Qian-Qian Du ◽  
Piao-Qin Cheng ◽  
Ting-Ting Yang ◽  
Chao-Qun Xing ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Dentate Gyrus ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Food Supplement ◽  
Lycium Barbarum ◽  
Neuroprotective Effects ◽  
Neuron Loss ◽  
Radiation Induced

Abstract Background: Brain exposure to ionizing radiation during the radiotherapy of brain tumor or metastasis of peripheral cancer cells to the brain has resulted in cognitive dysfunction by reducing neurogenesis in hippocampus. Methods: To demonstrate the radioprotective effect of lycium barbarum berry extract (Lyc), we evaluated the neurobehavioral alterations and the numbers of NeuN, calbindin (CB) and parvalbumin (PV) immunopositive hippocampal neurons in BALB/c mice after acute 5.5 Gy radiation with/without oral administration of Lyc at the dosage of 10 g/kg daily for 4 weeks. Results: The results showed that Lyc could improve irradiation-induced animal weight loss, depressive behaviors, spatial memory impairment and hippocampal neuron loss. Immunohistochemistry study demonstrated that the loss of NeuN-immunopositive neuron in the hilus of the dentate gyrus, CB-immunopositive neuron in CA1 strata radiatum, lacunosum moleculare and oriens, and PV-positive neuron in CA1 stratum pyramidum and stratum granulosum of the dentate gyrus after irradiation were significantly improved by Lyc treatment. Conclusions: The neuroprotective effect of Lyc on those hippocampal neurons may benefit the configuration of learning related neuronal networks and then improve radiation induced neurobehavioral changes such as cognitive impairment and depression. It suggests that lycium barbarum berry may be used as a potential radio-neuro-protective food supplement to prevent ionizing radiation induced neuron loss and neuropsychological disorders.

Neuroprotective and anti-amnestic effects of a combination therapy in a model of photochemical ischemic damage in the prefrontal cortex

2018 ◽  
pp. 39-45
Author(s):  
Ф.М. Шакова ◽  
Т.И. Калинина ◽  
М.В. Гуляев ◽  
Г.А. Романова
Keyword(s):  
Prefrontal Cortex ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Combination Therapy ◽  
Neuroprotective Effect ◽  
Regulatory Protein ◽  
Human Growth ◽  
Neuroprotective Effects ◽  
Nerve Growth

Цель исследования - изучение влияния комбинированной терапии (мутантные молекулы эритропоэтина (EPO) и дипептидный миметик фактора роста нервов ГК-2H) на воспроизведение условного рефлекса пассивного избегания (УРПИ) и объем поражения коры мозга у крыс с двусторонним ишемическим повреждением префронтальной коры. Методика. Мутантные молекулы EPO (MЕРО-TR и MЕPО-Fc) с значительно редуцированной эритропоэтической и выраженной цитопротекторной активностью созданы методом генной инженерии. Используемый миметик фактора роста нервов человека, эндогенного регуляторного белка, в экспериментах in vitro проявлял отчетливые нейропротективные свойства. Двустороннюю фокальную ишемию префронтальной коры головного мозга крыс создавали методом фотохимического тромбоза. Выработку и оценку УРПИ проводили по стандартной методике. Объем повреждения мозга оценивался при помощи МРТ. MEPO-TR и MEPO-Fc (50 мкг/кг) вводили интраназально однократно через 1 ч после фототромбоза, ГК-2Н (1 мг/кг) - внутрибрюшинно через 4 ч после фототромбоза и далее в течение 4 послеоперационных суток. Результаты. Выявлено статистически значимое сохранение выработанного до ишемии УРПИ, а также значимое снижение объема повреждения коры при комплексной терапии. Полученные данные свидетельствуют об антиамнестическом и нейропротекторном эффектах примененной комбинированной терапии, которые наиболее отчетливо выражены в дозах: МEPO-Fc (50 мкг/кг) и ГК-2Н (1 мг/кг). Заключение. Подтвержден нейропротекторный эффект и усиление антиамнестического эффекта при сочетанном применении мутантных производных эритропоэтина - MEPO-TR и MEPO-Fc и дипептидного миметика фактора роста нервов человека ГК-2H. The aim of this study was to investigate the effect of combination therapy, including mutant erythropoietin molecules (EPO) and a dipeptide mimetic of the nerve growth factor, GK-2H, on the conditioned passive avoidance (PA) reflex and the volume of injury induced by bilateral ischemia of the prefrontal cortex in rats. Using the method of genetic engineering the mutant molecules of EPO, MERO-TR and MEPO-Fc, with strongly reduced erythropoietic and pronounced cytoprotective activity were created. The used human nerve growth factor mimetic, an endogenous regulatory protein based on the b-bend of loop 4, which is a dimeric substituted dipeptide of bis- (N-monosuccinyl-glycyl-lysine) hexamethylenediamine, GK-2 human (GK-2H), has proven neuroprotective in in vitro experiments. Methods. Bilateral focal ischemic infarction was modeled in the rat prefrontal cortex by photochemically induced thrombosis. The PA test was performed according to a standard method. Volume of brain injury was estimated using MRI. MEPO-TR, and MEPO-Fc (50 mg/kg, intranasally) were administered once, one hour after the injury. GK-2Н (1 mg/kg, i.p.) was injected four hours after the injury and then for next four days. Results. The study showed that the complex therapy provided statistically significant retention of the PA reflex developed prior to ischemia and a significant decrease in the volume of injury. The anti-amnestic and neuroprotective effects of combination therapy were most pronounced at doses of MEPO-Fc 50 mg/kg and GK-2H 1 mg/kg. Conclusion. This study has confirmed the neuroprotective effect and enhancement of the anti-amnestic effect exerted by the combination of mutant erythropoietin derivatives, MEPO-TR and MEPO-Fc, and the dipeptide mimetic of human growth factor GK-2H.

Role of Rasayan Churna in outbreak of Covid -19 as preventive and curative aspect

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1208-1212
Author(s):  
Amol Madhav Deshpande ◽  
Mayuri Amol Deshpande
Keyword(s):  
Recurrent Infection ◽  
Symptomatic Patient ◽  
H1n1 Influenza ◽  
Drug Of Choice ◽  
Asymptomatic Patients ◽  
Diseased Person ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Immune Booster ◽  
Respiratory Droplets

In last two decade world suffer with three epidemic diseases like SARS-CoV, H1N1 influenza, MERS –CoV and presently the world under a pandemic of Covid-19, out of these SARS-CoV, MERS –CoV and Covid-19 are form the same virus call as corona, which primary present on bats and transferred from animal to human, and then it transfer from human to human mostly by respiratory droplets or in the direct contact with the diseased person, these recurrent infection of corona virus is the burning issue in the word, so to avoid these recurrent infections good habitual behaviour with regular immune booster medicine should be taken which can be used in both normal and symptomatic patient for this Rasayan churna  is the best drug of choice as it is used for  rejuvenation therapy. From literally study from various recourses it is found that Rasayan churna have property anti-depressant, anti-xylotic, Immunomodulatory, Anti-diabetes, anti hypertensive, anti-inflammatory, Anti-toxic effects, Anti-arthritic, Anti-cancer effects, Anti-microbial effect, and Anti-oxidant which can be useful in preventive aspect of Covid -19 in all phase like normal individual, also can be used in asymptomatic patients and symptomatic patients, clinical study can be performed for the same to evaluate the result.

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