scholarly journals PLGA Multiplex Membrane Platform for Disease Modelling and Testing of Therapeutic Compounds

Membranes ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 112
Author(s):  
Antonella Piscioneri ◽  
Sabrina Morelli ◽  
Enrico Drioli ◽  
Loredana De Bartolo

A proper validation of an engineered brain microenvironment requires a trade of between the complexity of a cellular construct within the in vitro platform and the simple implementation of the investigational tool. The present work aims to accomplish this challenging balance by setting up an innovative membrane platform that represents a good compromise between a proper mimicked brain tissue analogue combined with an easily accessible and implemented membrane system. Another key aspect of the in vitro modelling disease is the identification of a precise phenotypic onset as a definite hallmark of the pathology that needs to be recapitulated within the implemented membrane system. On the basis of these assumptions, we propose a multiplex membrane system in which the recapitulation of specific neuro-pathological onsets related to Alzheimer’s disease pathologies, namely oxidative stress and β-amyloid1–42 toxicity, allowed us to test the neuroprotective effects of trans-crocetin on damaged neurons. The proposed multiplex membrane platform is therefore quite a versatile tool that allows the integration of neuronal pathological events in combination with the testing of new molecules. The present paper explores the use of this alternative methodology, which, relying on membrane technology approach, allows us to study the basic physiological and pathological behaviour of differentiated neuronal cells, as well as their changing behaviour, in response to new potential therapeutic treatment.

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Xiangli Yan ◽  
Aiming Yu ◽  
Haozhen Zheng ◽  
Shengxin Wang ◽  
Yingying He ◽  
...  

Neuronal apoptosis induced by oxidative stress is a major pathological process that occurs after cerebral ischemia-reperfusion. Calycosin-7-O-β-D-glucoside (CG) is a representative component of isoflavones in Radix Astragali (RA). Previous studies have shown that CG has potential neuroprotective effects. However, whether CG alleviates neuronal apoptosis through antioxidant stress after ischemia-reperfusion remains unknown. To investigate the positive effects of CG on oxidative stress and apoptosis of neurons, we simulated the ischemia-reperfusion process in vitro using an immortalized hippocampal neuron cell line (HT22) and oxygen-glucose deprivation/reperfusion (OGD/R) model. CG significantly improved cell viability and reduced oxidative stress and neuronal apoptosis. In addition, CG treatment upregulated the expression of SIRT1, FOXO1, PGC-1α, and Bcl-2 and downregulated the expression of Bax. In summary, our findings indicate that CG alleviates OGD/R-induced damage via the SIRT1/FOXO1/PGC-1α signaling pathway. Thus, CG maybe a promising therapeutic candidate for brain injury associated with ischemic stroke.


2021 ◽  
pp. 1-17
Author(s):  
Mani Iyer Prasanth ◽  
James Michael Brimson ◽  
Dicson Sheeja Malar ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 375
Author(s):  
Jin Young Hong ◽  
Hyunseong Kim ◽  
Junseon Lee ◽  
Wan-Jin Jeon ◽  
Seung Ho Baek ◽  
...  

Inula britannica var. chinensis (IBC) has been used as a traditional medicinal herb to treat inflammatory diseases. Although its anti-inflammatory and anti-oxidative effects have been reported, whether IBC exerts neuroprotective effects and the related mechanisms in cortical neurons remain unknown. In this study, we investigated the effects of different concentrations of IBC extract (5, 10, and 20 µg/mL) on cortical neurons using a hydrogen peroxide (H2O2)-induced injury model. Our results demonstrate that IBC can effectively enhance neuronal viability under in vitro-modeled reaction oxygen species (ROS)-generating conditions by inhibiting mitochondrial ROS production and increasing adenosine triphosphate level in H2O2-treated neurons. Additionally, we confirmed that neuronal death was attenuated by improving the mitochondrial membrane potential status and regulating the expression of cytochrome c, a protein related to cell death. Furthermore, IBC increased the expression of brain-derived neurotrophic factor and nerve growth factor. Furthermore, IBC inhibited the loss and induced the production of synaptophysin, a major synaptic vesicle protein. This study is the first to demonstrate that IBC exerts its neuroprotective effect by reducing mitochondria-associated oxidative stress and improving mitochondrial dysfunction.


Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1019 ◽  
Author(s):  
Nur Zuliani Ramli ◽  
Mohamad Fairuz Yahaya ◽  
Ikuo Tooyama ◽  
Hanafi Ahmad Damanhuri

Nutraceuticals have been extensively studied worldwide due to its neuroprotective effects in in vivo and in vitro studies, attributed by the antioxidative properties. Alzheimer (AD) and Parkinson disease (PD) are the two main neurodegenerative disorders that are discussed in this review. Both AD and PD share the similar involvement of oxidative stress in their pathophysiology. Nutraceuticals exert their antioxidative effects via direct scavenging of free radicals, prevent damage to biomolecules, indirectly stimulate the endogenous antioxidative enzymes and gene expressions, inhibit activation of pro-oxidant enzymes, and chelate metals. In addition, nutraceuticals can act as modulators of pro-survival, pro-apoptotic, and inflammatory signaling pathways. They have been shown to be effective particularly in preclinical stages, due to their multiple mechanisms of action in attenuating oxidative stress underlying AD and PD. Natural antioxidants from food sources and natural products such as resveratrol, curcumin, green tea polyphenols, and vitamin E are promising therapeutic agents in oxidative stress-mediated neurodegenerative disease as they have fewer adverse effects, more tolerable, cheaper, and sustainable for long term consumption.


2020 ◽  
Vol 12 ◽  
Author(s):  
Zequn Yin ◽  
Xuerui Wang ◽  
Shihong Zheng ◽  
Peichang Cao ◽  
Yuanli Chen ◽  
...  

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It may be caused by oxidative stress, inflammation, and cerebrovascular dysfunctions in the brain. LongShengZhi Capsule (LSZ), a traditional Chinese medicine, has been approved by the China Food and Drug Administration for treatment of patients with cardiovascular/cerebrovascular disease. LSZ contains several neuroprotective ingredients, including Hirudo, Astmgali Radix, Carthami Flos (Honghua), Persicae Semen (Taoren), Acori Tatarinowii Rhizoma (Shichangpu), and Acanthopanax Senticosus (Ciwujia). In this study, we aimed to determine the effect of LSZ on the AD process. Double transgenic mice expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1) to model AD were treated with LSZ for 7 months starting at 2 months of age. LSZ significantly improved the cognition of the mice without adverse effects, indicating its high degree of safety and efficacy after a long-term treatment. LSZ reduced AD biomarker Aβ plaque accumulation by inhibiting β-secretase and γ-secretase gene expression. LSZ also reduced p-Tau expression, cell death, and inflammation in the brain. Consistently, in vitro, LSZ ethanol extract enhanced neuronal viability by reducing L-glutamic acid-induced oxidative stress and inflammation in HT-22 cells. LSZ exerted antioxidative effects by enhancing superoxide dismutase and glutathione peroxidase expression, reduced Aβ accumulation by inhibiting β-secretase and γ-secretase mRNA expression, and decreased p-Tau level by inhibiting NF-κB-mediated inflammation. It also demonstrated neuroprotective effects by regulating the Fas cell surface death receptor/B-cell lymphoma 2/p53 pathway. Taken together, our study demonstrates the antioxidative stress, anti-inflammatory, and neuroprotective effects of LSZ in the AD-like pathological process and suggests it could be a potential medicine for AD treatment.


2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Peng Wang ◽  
Qian Luo ◽  
Hui Qiao ◽  
Hui Ding ◽  
Yonggang Cao ◽  
...  

Chronic alcohol consumption causes hippocampal neuronal impairment, which is associated with oxidative stress and apoptosis. Carvacrol is a major monoterpenic phenol found in essential oils from the family Labiatae and has antioxidative stress and antiapoptosis actions. However, the protective effects of carvacrol in ethanol-induced hippocampal neuronal impairment have not been fully understood. We explored the neuroprotective effects of carvacrol in vivo and in vitro. Male C57BL/6 mice were exposed to 35% ethanol for 4 weeks to establish ethanol model in vivo, and hippocampal neuron injury was simulated by 200 mM ethanol in vitro. Morris water maze test was performed to evaluate the cognitive dysfunction. The oxidative stress injury of hippocampal neurons was evaluated by measuring the levels of oxidative stress biomarkers. Histopathological examinations and western blot were performed to evaluate the apoptosis of neurons. The results showed that carvacrol attenuates the cognitive dysfunction, oxidative stress, and apoptosis of the mice treated with ethanol and decreases hippocampal neurons apoptosis induced by ethanol in vitro. In addition, western blot analysis revealed that carvacrol modulates the protein expression of Bcl-2, Bax, caspase-3, and p-ERK, without influence of p-JNK and p-p38. Our results suggest that carvacrol alleviates ethanol-mediated hippocampal neuronal impairment by antioxidative and antiapoptotic effects.


2006 ◽  
Vol 3 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Yuta Inokuchi ◽  
Masamitsu Shimazawa ◽  
Yoshimi Nakajima ◽  
Shinsuke Suemori ◽  
Satoshi Mishima ◽  
...  

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retinain vitroand/orin vivo.In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In micein vivo, propolis (100 mg kg−1; intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitrealin vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage bothin vitroandin vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Nady Braidy ◽  
Subash Selvaraju ◽  
Musthafa Mohamed Essa ◽  
Ragini Vaishnav ◽  
Samir Al-Adawi ◽  
...  

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an environmental toxin which selectively induces oxidative damage and mitochondrial and proteasomal dysfunctions to dopaminergic neurons in the substantia nigra leading to Parkinsonian syndrome in animal models and humans. MPTP is one of the most widely usedin vitromodels to investigate the pathophysiology of Parkinson's disease (PD) and, screen for novel therapeutic compounds that can slow down or ameliorate this progressive degenerative disease. We investigated the therapeutic effect of pomegranate juice extracts (PJE), Helow, Malasi, Qusum, and Hamadh against MPTP-induced neurotoxicity in primary human neurons by examining extracellular LDH activity, intracellular NAD+and ATP levels, and endogenous antioxidant levels including lipid peroxidation products, catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) levels. MPTP induced a reduction in SOD and GPx activities and intracellular NAD+, ATP, and GSH levels parallel to an increase in extracellular LDH and CAT activities, although lipid peroxidation was not altered. We report that helow and malasi can ameliorate MPTP-induced neurotoxicity by attenuating the observed changes in redox function to a greater extent than qusum and hamedh. Selected PJE varieties may exhibit properties which may be of therapeutic value to slow down age-related degeneration and neurodegeneration in particular.


2000 ◽  
Vol 28 (5) ◽  
pp. A344-A344
Author(s):  
A. Fallarero ◽  
J. Loikkanen ◽  
O. Castaneda ◽  
A. Vidal ◽  
P. Mannisto

2021 ◽  
Author(s):  
Rafaella Carvalho Rossato ◽  
Alessandro Eustaquio Campos Granato ◽  
Jessica Cristina Pinto ◽  
Carlos Dailton Guedes de Oliveira Moraes ◽  
Geisa Nogueira Salles ◽  
...  

ABSTRACTAlzheimer’s disease (AD) is a type of dementia that affects millions of people. Although there is no cure, several study strategies seek to elucidate the mechanisms of the disease. Recent studies address the benefits of taurine. Thus, the present study aims to analyze the neuroprotective effect of taurine on human neuroblastoma, using an in vitro experimental model of oxidative stress induced by hydrocortisone in the SH-SY5Y cell line as a characteristic model of AD. The violet crystal assay was used for cell viability and the evaluation of cell morphology was performed by scanning electron microscopy (SEM). After pretreatment with taurine, the SH-SY5Y cell showed an improvement in cell viability in the face of oxidative stress and improved cell morphology. Thus, the treatment presented a neuroprotective effect.GRAPHICAL ABSTRACT


Sign in / Sign up

Export Citation Format

Share Document