Streptocyclinones A and B ameliorate Alzheimer's disease pathological processes in vitro

Alvariño, Rebeca; Albrecht, Eva; Lacret, Rodney; Oves-Costales, Daniel; Genilloud, Olga; Reyes, Fernando; Alfonso, Amparo; Botana, Luís M.

doi:10.1016/j.neuropharm.2018.09.008

Cited by 17 publications

(34 citation statements)

References 40 publications

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“…Experiments with BV2 microglial cells were performed as previously described . The levels of ROS were quantified with the fluorescence dye carboxy-H 2 DCFDA (5-(and-6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate).…”

Section: Methodsmentioning

confidence: 99%

Gracilin A Derivatives Target Early Events in Alzheimer’s Disease: in Vitro Effects on Neuroinflammation and Oxidative Stress

Alvariño

Albrecht

Abbasov

et al. 2019

ACS Chem. Neurosci.

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The search for compounds capable of targeting early pathological changes of Alzheimers disease (AD), such as oxidative stress and neuroinflammation, is an important challenge. Gracilin A derivatives were recently synthesized, using a pharmacophore-directed retrosynthesis (PDR) strategy, and found to possess potent neuroprotective effects. In this work, the previously described derivatives 1−7 which demonstrated mitochondrial-mediated, antioxidant effects were chosen for further study. The ability of compounds to modulate the expression of antioxidant genes (CAT, GPx, SODs, and Nrf 2) was determined in SH-SY5Y cells, and the simplified derivatives 2 and 3 were found to be the most effective. The anti-neuroinflammatory properties of all derivatives were assessed in BV2 microglial cells activated with lipopolysaccharide (LPS). Several derivatives decreased the release of cytokines (Il-1β, IL-6, GM-CSF, and TNF-α) and other damaging molecules (ROS, NO) and also regulated the translocation of Nrf2 and NFκB, and reduced p38 activation. These protective effects were confirmed in a trans-well coculture with BV2 and SH-SY5Y cells and several derivatives increased SH-SY5Y survival. This present work demonstrates the neuroprotective properties of gracilin A derivatives, making them promising candidate drugs for AD. Particularly, derivatives 2 and 3 showed the greatest potential as lead compounds for further development.

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Section: Methodsmentioning

confidence: 99%

Gracilin A Derivatives Target Early Events in Alzheimer’s Disease: in Vitro Effects on Neuroinflammation and Oxidative Stress

Alvariño

Albrecht

Abbasov

et al. 2019

ACS Chem. Neurosci.

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“…In Vitro Assays: Oxidative stress and neuroinflammation assays were performed in SH-SY5Y and BV2 cells, as previously described. [14,15] Further details are presented in Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective Effects of Apple‐Derived Drinks in a Mice Model of Inflammation

Alvariño

Albrecht

Alfonso

et al. 2019

Molecular Nutrition Food Res

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Scope: Fruit-derived drinks consumption is considered beneficial due to the antioxidant and neuroprotective effects of polyphenols separately, but studies including their total constituents are scarce. In this work, the antioxidant and anti-inflammatory neuroprotective effects of apple-derived beverages are determined in a mouse model of lipopolysaccharide (LPS)-induced inflammation. Methods and results: Preliminary antioxidant and neuroinflammatory experiments are carried out with 15 drink polyphenolic extracts in SH-SY5Y and BV2 cells, using H 2 O 2 as pro-oxidant and LPS as pro-inflammatory stimulus, respectively. Extracts improve antioxidant systems functioning and present neuroprotective mitochondrial-related effects. In microglia, extracts reduce reactive oxygen species and modulate cytokine release. To better mimic human consumption, four concentrated dealcoholized apple-derived drinks (three ciders and apple juice) are supplied to mice for 7 days in substitution of drinking water. Mice treated with beverages present reduced brain oxidative stress and inflammatory markers after LPS injection. Interestingly, genetic expression of antioxidant enzymes and glutathione levels are also greatly augmented after drink intake. Conclusion: The results confirm the antioxidant and anti-inflammatory-mediated neuroprotective properties of apple-derived drinks, suggesting that their consumption could be a good approach for prevention of neurodegenerative disorders. To the authors' knowledge, this is the first description of cider neuroprotective effects. Author ContributionsR.A. did in vitro and in vivo experiments. E.A. and A.A. performed in vivo assays and experimental design. L.M.B. did critical discussion and work design.

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“…Nrf2 is the principal transcription factor that regulates cell homeostasis related to oxidative and noxious stimuli by mediating the clearance of ROS via transcription of phase II anti-oxidant proteins ( Wardyn et al, 2015 ). Various natural products with known anti-inflammatory property successfully reduced the release of pro-inflammatory mediators by improving the Nrf2 level ( Alvariño et al, 2018 ; Luo et al, 2018 ; Wang et al, 2018 ; Xu et al, 2019 ; Zhou et al, 2019 ; Ma et al, 2020 ). Moreover, knockdown Nrf2 using Nrf2 siRNA in BV2 microglial cells has significantly reversed the inhibitory effects of cryptotanshinone (CTN), a monomer compound extracted from the dried roots and rhizomes of Salvia miltiorrhiza, on the release of M1 pro-inflammatory mediators, such as NO, cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), IL-1β, IL-6 and TNF-α.…”

Section: Hypoxiamentioning

confidence: 99%

Hypoxia-Induced Neuroinflammation in Alzheimer’s Disease: Potential Neuroprotective Effects of Centella asiatica

et al. 2021

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Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterised by the presence of extracellular beta-amyloid fibrillary plaques and intraneuronal neurofibrillary tau tangles in the brain. Recurring failures of drug candidates targeting these pathways have prompted research in AD multifactorial pathogenesis, including the role of neuroinflammation. Triggered by various factors, such as hypoxia, neuroinflammation is strongly linked to AD susceptibility and/or progression to dementia. Chronic hypoxia induces neuroinflammation by activating microglia, the resident immune cells in the brain, along with an increased in reactive oxygen species and pro-inflammatory cytokines, features that are common to many degenerative central nervous system (CNS) disorders. Hence, interests are emerging on therapeutic agents and plant derivatives for AD that target the hypoxia-neuroinflammation pathway. Centella asiatica is one of the natural products reported to show neuroprotective effects in various models of CNS diseases. Here, we review the complex hypoxia-induced neuroinflammation in the pathogenesis of AD and the potential application of Centella asiatica as a therapeutic agent in AD or dementia.

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Streptocyclinones A and B ameliorate Alzheimer's disease pathological processes in vitro

Cited by 17 publications

References 40 publications

Gracilin A Derivatives Target Early Events in Alzheimer’s Disease: in Vitro Effects on Neuroinflammation and Oxidative Stress

Gracilin A Derivatives Target Early Events in Alzheimer’s Disease: in Vitro Effects on Neuroinflammation and Oxidative Stress

Neuroprotective Effects of Apple‐Derived Drinks in a Mice Model of Inflammation

Hypoxia-Induced Neuroinflammation in Alzheimer’s Disease: Potential Neuroprotective Effects of Centella asiatica

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