A novel thiazolidinediones ATZD2 rescues memory deficits in a rat model of type 2 diabetes through antioxidant and antiinflammation

Wang, Xuankang; Sun, Ting; Li, Yujiao; Wang, Yuhong; Li, Yanjiao; Yang, Luting; Feng, Dan; Zhao, Ming; Wu, Yumei

doi:10.18632/oncotarget.22467

Cited by 12 publications

(9 citation statements)

References 40 publications

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“…The derivatives of thiazolidines, thiazoles and thiazolidinediones are molecules recognized in the literature for presenting a series of relevant pharmacological activities [ 1 , 2 , 3 ]. Among these activities are antimicrobial [ 3 , 4 ], antiviral [ 1 , 2 ], neurodegenerative [ 5 ], antitumor [ 6 , 7 ] and antioxidant [ 8 ] activities.…”

Section: Introductionmentioning

confidence: 99%

Neurolocomotor Behavior and Oxidative Stress Markers of Thiazole and Thiazolidinedione Derivatives against Nauphoeta cinerea

et al. 2022

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Thiazolidine compounds NJ20 {(E)-2-(2-(5-bromo-2-methoxybenzylidene)hydrazinyl)-4-(4-nitrophenyl)thiazole} and NW05 [(2-(benzo (d) (1,3) dioxol-4-ylmethylene)-N-(4-bromophenyl)-thiosemicarbazone] potentiated the effect of norfloxacin in resistant bacteria; however, there are no reports on their effects on Nauphoeta cinerea in the literature. The objective of this work was to evaluate the behavioral effects and oxidative markers of NW05 and NJ20 in lobster cockroach N. cinerea. To evaluate the behavioral study, a video tracking software was used to evaluate the locomotor points and the exploratory profile of cockroaches in the horizontal and vertical regions of a new environment. The total concentration of thiol and reduced glutathione (GSH), substances reactive to thiobarbituric acid (TBARS), free iron (II) content and mitochondrial viability were determined. The antioxidant potential was evaluated by the DPPH method. Both substances induced changes in the behavior of cockroaches, showing a significant reduction in the total distance covered and in the speed. In the cell viability test (MTT), there was a significant reduction for NJ20 (1 mM). NJ20 caused a significant increase in total levels of thiol and non-protein thiol (NPSH), although it also slightly increased the content of malondialdehyde (MDA). Both compounds (NW05 and NJ20) caused a significant reduction in the content of free iron at a concentration of 10 mM. In conclusion, the compound NJ20 caused moderate neurotoxicity (1 mM), but had good antioxidant action, while NW05 did not show toxicity or significant antioxidant activity in the model organism tested. It is desirable to carry out complementary tests related to the antioxidant prospection of these same compounds, evaluating them at different concentrations.

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Section: Introductionmentioning

confidence: 99%

Neurolocomotor Behavior and Oxidative Stress Markers of Thiazole and Thiazolidinedione Derivatives against Nauphoeta cinerea

et al. 2022

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“…36 According to the previously reported study, thiazolidine derivatives have tremendous potential to attenuate memory impairment and neuroinflammation. 67 Many published reports are evidencing the relationship between oxidative stress and stimulation of inflammatory cascades. [68][69][70] Increased oxidative stress and lower levels of antioxidant enzymes may have critical effects on brain tissues.…”

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confidence: 99%

Synthesis, In Silico and Pharmacological Evaluation of New Thiazolidine-4-Carboxylic Acid Derivatives Against Ethanol-Induced Neurodegeneration and Memory Impairment

Naz¹,

Kury²,

Nadeem³

et al. 2022

JIR

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Introduction Several studies revealed that alcohol utilization impairs memory in adults; however, the underlying mechanism is still unclear. The production of inflammatory markers and reactive oxygen species (ROS) plays a major role in neurodegeneration, which leads to memory impairment. Therefore, targeting neuroinflammation and oxidative distress could be a useful strategy for abrogating the hallmarks of ethanol-induced neurodegeneration. Moreover, several studies have demonstrated multiple biological activities of thiazolidine derivatives including neuroprotection. Methods In the current study, we synthesized ten (10) new thiazolidine-4-carboxylic acid derivatives (P1-P10), characterized their synthetic properties using proton nuclear magnetic resonance ( 1 H-NMR) and carbon-13 NMR, and further investigated the neuroprotective potential of these compounds in an ethanol-induced neuroinflammation model. Results Our results suggested altered levels of antioxidant enzymes associated with an elevated level of tumor necrosis factor-alpha (TNF-α), nuclear factor-κB (p-NF-κB), pyrin domain-containing protein 3 (NLRP3), and cyclooxygenase-2 (COX-2) in ethanol-treated animals. Ethanol treatment also led to memory impairment in rats, as assessed by behavioral tests. To further support our notion, we performed molecular docking studies, and all synthetic compounds exhibited a good binding affinity with a fair bond formation with selected targets (NF-κB, TLR4, NLRP3, and COX-2). Discussion Overall, our results revealed that these derivatives may be beneficial in reducing neuroinflammation by acting on different stages of inflammation. Moreover, P8 and P9 treatment attenuated the neuroinflammation, oxidative stress, and memory impairment caused by ethanol.

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“…A central question in the present work was whether the pro-cognitive and anti-neurodegenerative effects of Pio reflect direct actions in the brain or if they represent a collateral benefit of improved insulin sensitivity. Notably, some authors have also attributed the neuroprotective effects of TZD to their anti-inflammatory and/or -oxidative properties (Heneka et al, 2005, 2015; Wang X.K. et al, 2017; Zhang et al, 2017), phenomena that could help explain the purported role of activated PPARγ in a spectrum of neurological diseases (Zolezzi et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Activated PPARγ Abrogates Misprocessing of Amyloid Precursor Protein, Tau Missorting and Synaptotoxicity

Moosecker

Gomes

Dioli

et al. 2019

Front. Cell. Neurosci.

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Type 2 diabetes increases the risk for dementia, including Alzheimer’s disease (AD). Pioglitazone (Pio), a pharmacological agonist of the peroxisome proliferator-activated receptor γ (PPARγ), improves insulin sensitivity and has been suggested to have potential in the management of AD symptoms, albeit through mostly unknown mechanisms. We here investigated the potential of Pio to counter synaptic malfunction and loss, a characteristic of AD pathology and its accompanying cognitive deficits. Results from experiments on primary mouse neuronal cultures and a human neural cell line (SH-SY5Y) show that Pio treatment attenuates amyloid β (Aβ)-triggered the pathological (mis-) processing of amyloid precursor protein (APP) and inhibits Aβ-induced accumulation and hyperphosphorylation of Tau. These events are accompanied by increased glutamatergic receptor 2B subunit (GluN2B) levels that are causally linked with neuronal death. Further, Pio treatment blocks Aβ-triggered missorting of hyperphosphorylated Tau to synapses and the subsequent loss of PSD95-positive synapses. These latter effects of Pio are PPARγ-mediated since they are blocked in the presence of GW9662, a selective PPARγ inhibitor. Collectively, these data show that activated PPARγ buffer neurons against APP misprocessing, Tau hyperphosphorylation and its missorting to synapses and subsequently, synaptic loss. These first insights into the mechanisms through which PPARγ influences synaptic loss make a case for further exploration of the potential usefulness of PPARγ agonists in the prevention and treatment of synaptic pathology in AD.

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A novel thiazolidinediones ATZD2 rescues memory deficits in a rat model of type 2 diabetes through antioxidant and antiinflammation

Cited by 12 publications

References 40 publications

Neurolocomotor Behavior and Oxidative Stress Markers of Thiazole and Thiazolidinedione Derivatives against Nauphoeta cinerea

Neurolocomotor Behavior and Oxidative Stress Markers of Thiazole and Thiazolidinedione Derivatives against Nauphoeta cinerea

Synthesis, In Silico and Pharmacological Evaluation of New Thiazolidine-4-Carboxylic Acid Derivatives Against Ethanol-Induced Neurodegeneration and Memory Impairment

Activated PPARγ Abrogates Misprocessing of Amyloid Precursor Protein, Tau Missorting and Synaptotoxicity

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