Trilobatin attenuates cerebral ischaemia/reperfusion‐induced blood–brain barrier dysfunction by targeting matrix metalloproteinase 9: The legend of a food additive

British Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 181(7), P. 1005 - 1027

Published: Sept. 19, 2023

Abstract Background and Purpose Blood–brain barrier (BBB) breakdown is one of the crucial pathological changes cerebral ischaemia–reperfusion (I/R) injury. Trilobatin (TLB), a naturally occurring food additive, exerts neuroprotective effects against I/R injury as demonstrated in our previous study. This study was designed to investigate effect TLB on BBB disruption after Experimental Approach Rats with focal ischaemia caused by transient middle artery occlusion were studied along brain microvascular endothelial cells human astrocytes mimic oxygen glucose deprivation/reoxygenation (OGD/R). Key Results The results showed that effectively maintained integrity inhibited neuronal loss following challenge. Furthermore, increased tight junction proteins including ZO‐1, Occludin Claudin 5, decreased levels apolipoprotein E (APOE) 4, cyclophilin A (CypA) phosphorylated nuclear factor kappa B (NF‐κB), thereby reducing proinflammatory cytokines. also Bax/Bcl‐2 ratio cleaved‐caspase 3 reduced number apoptotic neurons. Molecular docking transcriptomics predicted MMP9 prominent gene evoked treatment. protective I/R‐induced largely abolished overexpression MMP9, beneficial OGD/R‐induced astrocyte co‐cultures markedly reinforced knockdown MMP9. Conclusions Implications Our findings reveal novel property TLB: preventing via targeting inhibiting APOE4/CypA/NF‐κB axis.

Language: Английский

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Network Pharmacology and Molecular Docking Analyses Unveil the Mechanisms of Yiguanjian Decoction against Parkinson’s Disease from Inner/Outer Brain Perspective

BioMed Research International, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 25

Published: Sept. 26, 2022

This study aims to explore the pharmacodynamic mechanism of Yiguanjian (YGJ) decoction against Parkinson's disease (PD) through integrating central nervous (inner brain) and peripheral system (outer relationship spectrum.The active components YGJ were achieved from TCMSP, TCMID, TCM@Taiwan databases. The blood-brain barrier (BBB) permeability along with their corresponding targets was evaluated utilizing existing website, namely, SwissADME SwissTargetPrediction. PD determined database retrieval. interaction network constructed upon STRING database, followed by visualization using Cytoscape software. Then, we performed Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses on potential targets. Finally, molecular docking approach employed assess binding affinity between key targets.Overall, identified 79 components, 128 YGJ, 97 YGJ-BBB potentially suitable for treatment PD. GO KEGG showed that mainly relied PI3K-Akt pathway while mostly involved in endocrine resistance. results displayed high multiple compounds accordance previous observations.Our unveiled mechanisms a systemic perspective: (1) they have exerting effects inhibiting neuronal apoptosis regulating pathway; (2) YGJ-BBB, can directly modulate resistance holistically enhance body pathway.

Language: Английский

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Ethnopharmacological validation of Karkataka Taila-An edible crab Rasayana in rotenone-induced in vitro and in vivo models of Parkinson's disease

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 335, P. 118691 - 118691

Published: Aug. 10, 2024

Language: Английский

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Silent Information Regulator 1/Peroxisome Proliferator‐Activated Receptor‐γ Coactivator‐1α Axis: A Promising Target for Parkinson's and Alzheimer's Disease Therapies

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(12)

Published: Dec. 1, 2024

ABSTRACT One of the key challenges in medical research is developing safe medications to treat neurodegenerative disorders. Increased oxidative stress, mitochondrial dysfunction, and neuroinflammation are common features Alzheimer's disease (AD) Parkinson's (PD). Silent information regulator 1 (SIRT‐1), part sirtuin family, plays a critical role various physiological processes by binding histones nonhistone proteins. SIRT‐1 primarily mitigates stress regulates activity maintaining deacetylated form peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α), ensuring stable PGC‐1α levels. Research has shown reduced SIRT‐1/PGC‐1α expression AD PD models. Targeting this pathway presents promising therapeutic approach for managing PD, potentially leading disease‐modifying treatments improved outcomes. This review highlights findings studies suggesting that promotes biogenesis, synaptic plasticity, cognitive function, as well exerts antioxidant, anti‐inflammatory, anti‐apoptotic effects, offering potential method treatment.

Language: Английский

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Role of Apoptosis in Neurodegeneration: Therapeutic Targets and Strategies

Published: Jan. 1, 2024

Language: Английский

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