Neuroinflammatory In Vitro Cell Culture Models and the Potential Applications for Neurological Disorders

Peng, Ye; Chu, Shifeng; Yang, Yantao; Zhang, Zhao; Pang, Zhigang; Chen, Nai‐Hong

doi:10.3389/fphar.2021.671734

Cited by 47 publications

(34 citation statements)

References 128 publications

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“…Besides, and in order to predict any neurotoxic effect of the extract, the neuroblastoma SH-SY5Y cell line was also employed. This model is widely used in in vitro studies of neurological disorders, such as AD, ischemia, or neurotoxicity ( 85 ). Moreover, these cells can be differentiated and acquire mature neuron-like features, thus becoming phenotypically closer to primary neurons ( 40 ).…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective Potential of Tamarillo (Cyphomandra betacea) Epicarp Extracts Obtained by Sustainable Extraction Process

et al. 2021

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Tamarillo (Cyphomandra betacea (Cav.) Sendt.), or tree tomato, is a tropical fruit from the Andean region of South America; it is highly rich in vitamins, minerals, and polyphenolic compounds. In this study, extracts from tamarillo epicarp (TE) were obtained by pressurized liquid extraction (PLE), and their in-vitro neuroprotective potential was assessed. A central composite design with response surface methodology was performed to optimize PLE as a function of solvent composition and temperature. Selected response variables were extraction yield, total phenolic content (TPC), total flavonoid content (TFC), total carotenoid content (TCC), antioxidant (ABTS), and anti-inflammatory (LOX) activities, and anti-acetylcholinesterase (AChE) inhibitory capacity. According to the desirability function, the optimal conditions were 100% ethanol and 180°C with a 0.87 desirability value. Next, the anti-butyrylcholinesterase enzyme (BChE), reactive oxygen species (ROS), and reactive nitrogen species (RNS) inhibition as well as cytotoxicity in HK-2, THP-1 monocytes, and SH-5YSY neuroblastoma cell lines were studied for the TE extract obtained under optimized conditions. The optimum TE extract provided the following results: extraction yield (36.25%), TPC (92.09 mg GAE/g extract), TFC (4.4 mg QE/g extract), TCC (107.15 mg CE/g extract), antioxidant capacity (ABTS, IC50 = 6.33 mg/ml extract), LOX (IC50 = 48.3 mg/ml extract), and AChE (IC50 = 97.46 mg/ml extract), and showed no toxicity at concentration up to 120 μg/ml extract for all the tested cell lines. Finally, chemical characterization by liquid chromatography-tandem mass spectrometry (UHPLC-q-TOF-MS/MS) of the optimum TE extract exhibited an important presence of hydroxycinnamic acid derivatives and other phenolic acids as well as quercetin hexoside and rutin, as main metabolites responsible for the observed biological properties. All these results suggested that TE, which represents between 8 and 15% of the total fruit, could become a promising natural by-product with a potential “multitarget” activity against Alzheimer's disease.

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Section: Resultsmentioning

confidence: 99%

Neuroprotective Potential of Tamarillo (Cyphomandra betacea) Epicarp Extracts Obtained by Sustainable Extraction Process

et al. 2021

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“…These problems were overcome by using 3D cultures, organoids, scaffolds, microfluidics platform to mimic blood flow etc. Cell systems mimicking the blood-brain barrier has been recently reviewed by Peng et al (2021) . Neuroinflammation associated with neurodegeneration can be mimicked by more advanced 3D glial cell culture systems as well as co-culture of microglia, neuroblastoma and endothelial cells ( Tu et al, 2019 ; Yin et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Role of Specialized Pro-resolving Mediators in Reducing Neuroinflammation in Neurodegenerative Disorders

Ponce

Ulu

Hanson

et al. 2022

Front. Aging Neurosci.

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Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders that affect millions of individuals worldwide. As incidence of these conditions increases with age, there will undoubtedly be an increased prevalence of cases in the near future. Neuroinflammation is a hallmark in the development and progression of neurodegenerative diseases and prevention or resolution of chronic neuroinflammation may represent a novel approach to treatment. The present review highlights the potential of the anti-inflammatory and pro-resolving effects of polyunsaturated fatty acid (PUFA)-derived mediators (Specialized Pro-resolving Mediators—SPM) in neurodegenerative disorders. PUFA-derived SPM are biosynthesized in response to chemicals produced from acute inflammatory responses. Preclinical studies from both AD and PD models suggest a dysregulation of SPM and their receptors in neurological disorders. Decreased SPM may be due to inadequate substrate, an imbalance between SPM and pro-inflammatory mediators or a disruption in SPM synthesis. SPMs hold great promise for neuroprotection in AD by altering expression of pro-inflammatory genes, modulating macrophage function, serving as a biomarker for AD status, and promoting resolution of neuroinflammation. In PD, data suggest SPM are able to cross the blood-brain barrier, inhibit microglial activation and decrease induced markers of inflammation, possibly as a result of their ability to downregulate NFκB signaling pathways. Several in vivo and in vitro studies suggest a benefit from administration of SPMs in both neurodegenerative disorders. However, extrapolation of these outcomes to humans is difficult as no models are able to replicate all features of AD or PD. Minimal data evaluating these PUFA-derived metabolites in humans with neurodegenerative disorders are available and a gap in knowledge exists regarding behavior of SPM and their receptors in patients with these conditions. There is also large gap in our knowledge regarding which lipid mediator would be most effective in which model of AD or PD and how dietary intake or supplementation can impact SPM levels. Future direction should include focused, translational efforts to investigate SPM as an add-on (in addition to standard treatment) or as standalone agents in patients with neurodegenerative disorders.

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“…Neuroinflammation has become a popular topic in neurological research in recent years, with a focus on the activation and inflammatory response of astrocytes and microglia, making neuron and glial cell models important study tools for neurodegenerative diseases [ 123 ]. Although the Cpn-induced neuroinflammation model is one of these tools, its utilization has limitations like other in vitro co-culture methods.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of some epigenetic modifying drugs’ on Chlamydia pneumoniae-induced neuroinflammation: A novel model

Tilki

Dikmen

2021

PLoS ONE

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Chlamydia pneumoniae (Cpn) is a gram-negative intracellular pathogen that causes a variety of pulmonary diseases, and there is growing evidence that it may play a role in Alzheimer’s disease (AD) pathogenesis. Cpn can interact functionally with host histones, altering the host’s epigenetic regulatory system by introducing bacterial products into the host tissue and inducing a persistent inflammatory response. Because Cpn is difficult to propagate, isolate, and detect, a modified LPS-like neuroinflammation model was established using lyophilized cell free supernatant (CFS) obtained from infected cell cultures, and the effects of CFS were compared to LPS. The neuroprotective effects of Trichostatin A (TSA), givinostat, and RG108, which are effective on epigenetic mechanisms, and the antibiotic rifampin, were studied in this newly introduced model and in the presence of amyloid beta (Aβ) 1–42. The neuroprotective effects of the drugs, as well as the effects of CFS and LPS, were evaluated in Aβ-induced neurotoxicity using a real-time cell analysis system, total ROS, and apoptotic impact. TSA, RG108, givinostat, and rifampin all demonstrated neuroprotective effects in both this novel model and Aβ-induced neurotoxicity. The findings are expected to provide early evidence on neuroprotective actions against Cpn-induced neuroinflammation and Aβ-induced neurotoxicity, which could represent a new treatment option for AD, for which there are currently few treatment options.

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Neuroinflammatory In Vitro Cell Culture Models and the Potential Applications for Neurological Disorders

Cited by 47 publications

References 128 publications

Neuroprotective Potential of Tamarillo (Cyphomandra betacea) Epicarp Extracts Obtained by Sustainable Extraction Process

Neuroprotective Potential of Tamarillo (Cyphomandra betacea) Epicarp Extracts Obtained by Sustainable Extraction Process

Role of Specialized Pro-resolving Mediators in Reducing Neuroinflammation in Neurodegenerative Disorders

Neuroprotective effects of some epigenetic modifying drugs’ on Chlamydia pneumoniae-induced neuroinflammation: A novel model

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