Indirubin Derivative 7-Bromoindirubin-3-Oxime (7Bio) Attenuates Aβ Oligomer-Induced Cognitive Impairments in Mice

doi:10.3389/fnmol.2017.00393

Paper

Indirubin Derivative 7-Bromoindirubin-3-Oxime (7Bio) Attenuates Aβ Oligomer-Induced Cognitive Impairments in Mice

Published Nov 28, 2017 · Li-ping Chen, Chunhui Huang, Jieyi Shentu

Frontiers in Molecular Neuroscience

Q2 SJR score

16

Citations

0

Influential Citations

Full textSemantic Scholar

Abstract

Indirubins are natural occurring alkaloids extracted from indigo dye-containing plants. Indirubins could inhibit various kinases, and might be used to treat chronic myelocytic leukemia, cancer and neurodegenerative disorders. 7-bromoindirubin-3-oxime (7Bio), an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β), two pharmacological targets of Alzheimer's disease (AD). In this study, we have discovered that 2.3–23.3 μg/kg 7Bio effectively prevented β-amyloid (Aβ) oligomer-induced impairments of spatial cognition and recognition without affecting bodyweight and motor functions in mice. Moreover, 7Bio potently inhibited Aβ oligomer-induced expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, 7Bio significantly prevented the decreased expression of synapsin-1 and PSD-95, biomarkers of pre-synaptic and post-synaptic proteins in Aβ oligomer-treated mice. The mean optical density (OD) with hyper-phosphorylated tau (pTau), glial fibrillary acidic protein (GFAP) and CD45 positive staining in the hippocampus of 7Bio-treated mice were significantly decreased compared to those of Aβ oligomer-treated mice. In addition, Western blotting analysis showed that 7Bio attenuated Aβ oligomer-decreased expression of pSer9-GSK3β. Those results suggested that 7Bio could potently inhibit Aβ oligomer-induced neuroinflammation, synaptic impairments, tau hyper-phosphorylation, and activation of astrocytes and microglia, which may contribute to the neuroprotective effects of 7Bio. Based on these findings, we expected that 7Bio might be developed as a novel anti-AD lead compound.

Non-RCT

Animal Study

Study Snapshot

7-bromoindirubin-3-oxime (7Bio) effectively prevents cognitive impairments and neuroinflammation caused by -amyloid oligomers in mice, suggesting potential as a novel anti-Alzheimer's disease lead compound.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Indirubin Derivative 7-Bromoindirubin-3-Oxime (7Bio) Attenuates Aβ Oligomer-Induced Cognitive Impairments in Mice

Sign up to use Study Snapshot

References

Impaired neurovascular coupling in aging and Alzheimer's disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline

Aging impairs neurovascular coupling, leading to cognitive decline and dementia, with astrocyte dysfunction and endothelial impairment playing a role.

5-Hydroxycyclopenicillone, a New β-Amyloid Fibrillization Inhibitor from a Sponge-Derived Fungus Trichoderma sp. HPQJ-34

5-hydroxycyclopenicillone, a newly discovered cyclopentenone, has moderate anti-oxidative properties, anti-A fibrillization properties, and neuroprotective effects, potentially serving as a good free radical scavenger.

Fucoxanthin Inhibits β-Amyloid Assembly and Attenuates β-Amyloid Oligomer-Induced Cognitive Impairments.

Fucoxanthin effectively inhibits -amyloid assembly and reduces neurotoxicity, potentially improving Alzheimer's disease by reducing neurotoxicity and oxidative stress.

Indirubin improves antioxidant and anti-inflammatory functions in lipopolysaccharide-challenged mice

Indirubin alleviates LPS-induced acute lung injury in mice by improving antioxidant and anti-inflammatory functions, potentially through NO and NF-B signals.

Fucoxanthin prevents H2O2-induced neuronal apoptosis via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway

Fucoxanthin protects against hydrogen peroxide-induced neuronal apoptosis by activating the PI3-K/Akt cascade and inhibiting the ERK pathway, offering potential for treating neurodegenerative disorders caused by oxidative stress.

Citations

Molecular Docking and Dynamics Simulation Studies Predict Potential Anti-ADAR2 Inhibitors: Implications for the Treatment of Cancer, Neurological, Immunological and Infectious Diseases

Potential anti-ADAR2 inhibitors show promising potential for treating neurological disorders, some cancers, and viral infections caused by RNA viruses.

Sulforaphene, a CDK5 Inhibitor, attenuates cognitive deficits in a transgenic mouse model of Alzheimer's disease via reducing Aβ Deposition, tau hyperphosphorylation and synaptic dysfunction.

Sulforaphene, a CDK5 inhibitor, improves cognitive deficits in Alzheimer's disease mice by reducing A deposition, tau hyperphosphorylation, and synaptic dysfunction.

New insights into the characteristics of DRAK2 and its role in apoptosis: From molecular mechanisms to clinically applied potential

DRAK2 plays a crucial role in regulating apoptosis and related diseases, with potential for clinical application of DRAK2-based inhibitors in various cancers and non-tumor diseases.

Indirubin-3’-monoxime-loaded PLGA-PEG nanoparticles for potential Alzheimer’s disease treatment

PLGA-PEG-I3M nanoparticles show potential as a promising Alzheimer's disease treatment due to their sustained release and improved neuroprotective activity against A oligomers-induced neuronal death.

Dendrobium nobile Lindl. Alkaloids Ameliorate Aβ25-35-Induced Synaptic Deficits by Targeting Wnt/β-Catenin Pathway in Alzheimer's Disease Models.

DNLA effectively protects synaptic integrity and prevents amyloidogenesis in Alzheimer's disease models by activating the Wnt/-catenin signaling pathway.

Altered expression of miR-29a-3p and miR-34a-5p by specific inhibition of GSK3β in the MPP+ treated SH-SY5Y Parkinson's model

7-BIO inhibition of GSK3 alleviates MPP+-induced neurotoxicity by regulating miR-29a-3p and miR-34a-5p expressions in Parkinson's disease model SH-SY5Y cells.

PLGA-PEG Nanoparticles Facilitate In Vivo Anti-Alzheimer's Effects of Fucoxanthin, a Marine Carotenoid Derived from Edible Brown Algae.

PLGA-PEG nanoparticles enhance the bioavailability of fucoxanthin and potentiate its efficacy for treating Alzheimer's disease, potentially enabling its future use in Alzheimer's therapy.

Dimeric Tacrine (10)-Hupyridone Effectively Combats Alzheimer’s Disease as A Multi-Target-Directed Ligand

A10E shows potential as a multi-target-directed ligand for Alzheimer's disease treatment by inhibiting A aggregation, activating BDNF/TrkB pathway, reducing neuroinflammation, and decreasing AChE activity.

Magnolol Ameliorates Behavioral Impairments and Neuropathology in a Transgenic Mouse Model of Alzheimer's Disease

Magnolol, the main active ingredient in Magnolia officinalis, can improve cognitive deficits in Alzheimer's disease mice by suppressing neuroinflammation, amyloid pathology, and synaptic dysfunction.