Polysaccharide from Ganoderma sinense improves cognitive capacity in a mouse model of Alzheimer’s disease via reshaping the gut microbiota and short-chain fatty acid metabolism DOI Creative Commons
Wenjuan Bian, Jiaxuan Wang,

Yudi Jin

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Abstract Two types of polysaccharides from Ganoderma sinense termed GSP1 (Mw: 58.92 kDa, consisting fourteen monosaccharides) and GSP2 3.27 were purified, their protective effects against Alzheimer's disease (AD) in a mouse model investigated. An vitro study suggested that GSPs protect SH-SY5Y cells neurotoxicity oxidative stress response to glutamate. The effect on the cognitive memory capacity AD was confirmed using Morris Water Maze, Object Recognition, Nestlet Shredding tests. Additionally, treatment with could reduce amyloid β plaques brains mice. Multi-omics analysis gut microbiome, short-chain fatty acid (SCFAs) metabolomics, behavioral tests conducted elucidate therapeutic mechanisms GSPs. results revealed improved diversity restored structure microflora, regulated SCFA metabolism. Four genera (Turicibacter, Jeotgalicoccus, Staphylococcusa, Odoribacter) significantly associated both SCFAs metabolism GSP1-treated group. These findings provide basis for development polysaccharide drugs further GSP1.

Language: Английский

Rational drug repurposing for alzheimer’s treatment using in-silico ligand and structure-based approaches DOI Creative Commons
Karishma Rathi, Ravindra D. Wavhale, Ritesh P. Bhole

et al.

Brazilian Journal of Pharmaceutical Sciences, Journal Year: 2024, Volume and Issue: 60

Published: Jan. 1, 2024

Alzheimer’s disease is a devastating neurodegenerative disorder characterized by memory loss and cognitive decline. New AD treatments are essential, drug repositioning promising approach. In this study, we combined ligand-based structure-based approaches to identify potential candidates among FDA-approved drugs for treatment. We used the human acetylcholinesterase receptor structure (PDB ID: 4EY7) applied Rapid Overlay of Chemical Structures Swiss Similarity screening.Computational shape-based screening revealed 20 out 760 FDA approved with structural similarity Donepezil, an treatment AChE inhibitor query molecule. The screened hits were further analyzed using docking analysis Autodock Vina Schrodinger glide. Predicted binding affinities guided prioritization candidates. Doxazosin, Oxypertine, Cyclopenthiazide, Mestranol, Terazosin exhibited favorable properties in shape similarity, energy, molecular dynamics stability.Molecular simulations confirmed stability complexes over 100 ns. Binding free energy MM-GBSA indicated favourable energies selected drugs. ADME, formulation studies offered insights into therapeutic applications predicted toxicity.This comprehensive computational approach identified (especially Doxazosin) as repurposing treatment, warranting investigation clinical assessment.

Language: Английский

Citations

1
Nebivolol, an antihypertensive agent, has new application in inhibiting melanoma DOI Creative Commons
Shuping Yang, Zhi Li,

Jiamei Yi

et al.

Anti-Cancer Drugs, Journal Year: 2024, Volume and Issue: unknown

Published: April 11, 2024

Repurposing existing drugs for cancer therapy has become an important strategy because of its advantages, such as cost reduction, effect and safety. The present study was designed to investigate the antimelanoma possible mechanisms action nebivolol, which is approved widely prescribed antihypertensive agent. In this study, we explored nebivolol on cell proliferation activity in melanoma vitro potential mechanism through a series experiments, including analysis effects with regard apoptosis metastasis. Furthermore, evaluated xenograft tumor models inspected vivo using immunohistochemical immunofluorescence staining assays. As results work, , possessed strong suppression cycle arrest melanoma. Moreover, significantly induced mitochondrial-mediated endogenous pathway. Additionally, inhibited More importantly, exhibited effective related induction, inhibition, metastasis blocking angiogenesis arrest. Overall, data recommend that holds great application novel agent treatment

Language: Английский

Citations

1
Direct Interaction of Minocycline to p47phox Contributes to its Attenuation of TNF-α-Mediated Neuronal PC12 Cell Death: Experimental and Simulation Validation DOI
Habib Eslami,

Koosha Rokhzadi,

Mohsen Basiri

et al.

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 82(2), P. 1261 - 1277

Published: May 13, 2024

Language: Английский

Citations

1
Synthesis and cholinesterases inhibitory effects of water soluble zinc(II) and silicon(IV) phthalocyanines bearing ({8‐[3‐(dimethylamino)phenoxy]octyl}oxy) groups DOI Creative Commons

Berna Usta,

Gökçe Seyhan, Didem Akkaya

et al.

Applied Organometallic Chemistry, Journal Year: 2024, Volume and Issue: 38(11)

Published: July 19, 2024

Alzheimer's disease, is one of the irreversible neurodegenerative disorders among older people, causes behavior, memory, and thinking problems. This study aim to synthesize 4‐({8‐[3‐(dimethylamino)phenoxy]octyl}oxy)phthalonitrile, zinc(II) phthalocyanine its water soluble derivative containing ({8‐[3‐(dimethylamino)phenoxy]octyl}oxy) substituents at peripheral positions first time. To determine potential silicon(IV) phthalocyanines for use in AD, spectrophotometric assays were performed their acetylcholinesterase/butyrylcholinesterase inhibitory effects. In addition, DNA nuclease properties evaluated by agarose gel electrophoresis. The results showed that compounds inhibited acetylcholinesterase/butyrylcholinesterase. They did not damage pBR322 plasmid depending on time concentration. As a result experiments, it revealed may be as cholinesterase inhibitors, which promising approach treatment disease.

Language: Английский

Citations

1
Omaveloxolone Ameliorates Cognitive Deficits by Inhibiting Apoptosis and Neuroinflammation in APP/PS1 Mice DOI
Zhao‐Jun Liu, Jianping Jia

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

Citations

1
Cysteine sulfenylation contributes to liver fibrosis via the regulation of EphB2-mediated signaling DOI Creative Commons

Yueqing Han,

Qi Gao,

Yating Xu

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Aug. 20, 2024

Sulfenylation is a reversible oxidative posttranslational modification (PTM) of proteins on cysteine residues. Despite the dissection various biological functions sulfenylation, its roles in hepatic fibrosis remain elusive. Here, we report that EphB2, receptor tyrosine kinase previously implicated liver fibrosis, regulated by sulfenylation during fibrotic progression liver. Specifically, EphB2 sulfenylated at residues Cys636 and Cys862 activated stellate cells (HSCs), leading to elevation activity protein stability stronger interactions with focal adhesion for activation downstream mitogen-activated signaling. The inhibitions both idebenone (IDE), marketed drug potent antioxidant activity, can markedly suppress HSCs ameliorate injury two well-recognized mouse models fibrosis. Collectively, this study reveals as new type PTM sheds light therapeutic potential IDE treatment

Language: Английский

Citations

1
Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease DOI Creative Commons

Andrea Bagán,

Sergio Rodríguez‐Arévalo, Teresa Taboada

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(10), P. 2381 - 2381

Published: Sept. 25, 2023

Humanity is facing a vast prevalence of neurodegenerative diseases, with Alzheimer's disease (AD) being the most dominant, without efficacious drugs, and only few therapeutic targets identified. In this scenario, we aim to find molecular entities that modulate imidazoline I2 receptors (I2-IRs) have been pointed out as relevant in AD. work, explored structural modifications well-established I2-IR ligands, giving access derivatives an imidazole-linked heterocycle common key feature. We report synthesis, affinity human I2-IRs, brain penetration capabilities, silico ADMET studies, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies new bunch ligands. Selected compounds showed neuroprotective properties beneficial effects vitro model Parkinson's disease, rescued dopaminergic cell line SH-SY5Y from death after treatment 6-hydroxydopamine, crucial anti-inflammatory cellular neuroinflammation. After preliminary pharmacokinetic study, action our representative 2-(benzo[b]thiophen-2-yl)-1H-imidazole LSL33 mouse AD (5xFAD). Oral administration at 2 mg/Kg for 4 weeks ameliorated 5XFAD cognitive impairment synaptic plasticity, well reduced neuroinflammation markers. summary, ligand promoted should be considered promising strategy neurodegeneration.

Language: Английский

Citations

3
BNIP1 inhibits the fusion of autophagosome and lysosome in hippocampal neurons and promotes the development of Alzheimer's disease DOI Creative Commons
Chen Li, Miao Zhang, Hongyan Xia

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 7, 2024

Abstract Background BNIP1 (BCL2 interacting protein 1) is a soluble N-ethyl maleimide sensitive factor attachment receptor, and its decreased expression potentially associated with the occurrence development of Alzheimer's disease (AD), regulation has potential significance for prevention treatment AD. Methods The was detected in APP/PS1 transgenic mice APP-overexpressed HT22 hippocampal nerve cells. most relevant components were investigated by mass spectrometry. After using small interfering RNA plasmid to regulate BNIP1, detection results strengthened ensure accuracy reliability experiment. Results In our study, we that decrease double-transgenic cells inhibited fusion autophagosome lysosome, further induced Rab7 Rab5b recruitment. Overexpression can promote lysosome. knockdown resulted dysfunction lysosome Conclusions These suggest lead dysfusion AD while overexpression ultimately inducing recruit Rab7, which provides intervention target

Language: Английский

Citations

0
Alzheimer's disease: current concept and a new hope with siRNA-liposomal system DOI
Kawthar K. Abla,

Mohammad K. Zahwi

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 102, P. 106409 - 106409

Published: Nov. 13, 2024

Language: Английский

Citations

0
Polysaccharide from Ganoderma sinense improves cognitive capacity in a mouse model of Alzheimer’s disease via reshaping the gut microbiota and short-chain fatty acid metabolism DOI Creative Commons
Wenjuan Bian, Jiaxuan Wang,

Yudi Jin

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Abstract Two types of polysaccharides from Ganoderma sinense termed GSP1 (Mw: 58.92 kDa, consisting fourteen monosaccharides) and GSP2 3.27 were purified, their protective effects against Alzheimer's disease (AD) in a mouse model investigated. An vitro study suggested that GSPs protect SH-SY5Y cells neurotoxicity oxidative stress response to glutamate. The effect on the cognitive memory capacity AD was confirmed using Morris Water Maze, Object Recognition, Nestlet Shredding tests. Additionally, treatment with could reduce amyloid β plaques brains mice. Multi-omics analysis gut microbiome, short-chain fatty acid (SCFAs) metabolomics, behavioral tests conducted elucidate therapeutic mechanisms GSPs. results revealed improved diversity restored structure microflora, regulated SCFA metabolism. Four genera (Turicibacter, Jeotgalicoccus, Staphylococcusa, Odoribacter) significantly associated both SCFAs metabolism GSP1-treated group. These findings provide basis for development polysaccharide drugs further GSP1.

Language: Английский

Citations

0