Dl-3-n-butylphthalide attenuates cerebral ischemia/reperfusion injury in mice through AMPK-mediated mitochondrial fusion

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 22, 2024

Introduction: NBP is a compound isolated from celery seeds, which was approved by the National Medical Products Administration in 2002 for clinical treatment of ischemic stroke. However, brain ischemia/reperfusion (I/R) injury, related research on mitochondrial dynamics and its mechanism action still need to be further studied. The aim this study assess cerebral pathology stroke vivo , with specific focus molecular mechanisms how promotes fusion. Methods: Male C57BL/6 mice were utilized subjected middle artery occlusion/reperfusion (MCAO/R). Pre-ischemia, administered through intraperitoneal (i.p.) injection 7 days. Results: Our findings demonstrated that effectively reduced infarct volume, improved neurological dysfunction, enhanced blood flow, promoted fusion MCAO/R. More importantly, pro-fusion effects found linked activation AMPK/Mfn1 pathway, function, partially eliminated inhibitors AMPK. Discussion: results revealed novel promoter protecting against AMPK-mediated Mfn1. These contribute understanding involved protection function following

Language: Английский

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In silico identification of novel ligands targeting stress-related human FKBP5 protein in mental disorders

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0320017 - e0320017

Published: March 17, 2025

FK506-binding protein 51 (FKBP51 or FKBP5) serves as a crucial stress modulator implicated in mental disorders, presenting potential target for intervention. Inhibitors like SAFit2, rapamycin, and tacrolimus exhibit promising interactions with this protein. Despite these advances, challenges persist diversifying FKBP5 ligands, prompting further exploration of interaction partners. Hence, study aims to identify other ligands. Employing molecular docking, we generated complexes various ligands (rapamycin, tacrolimus, SAFit2-Selective antagonist FKBP51 by induced fit, ascomycin, pimecrolimus, rosavin, salidroside, curcumin, apigenin, uvaricin, ruscogenin, neoruscogenin, pumicalagin, castalagin, grandinin). We identified the top 3 best which ruscogenin neoruscogenin had notable abilities cross blood-brain barrier have high gastrointestinal absorption, curcumin. Toxicity predictions show be least toxic based on oral toxicity classification (Class VI). Tyrosine (Tyr113) formed consistent all complex, reinforcing their involvement modulation. Molecular dynamic (MD) simulation validated strong between our three key provided an understanding stability complex. The binding free energy (ΔG) (based pharmacological properties) from MD analysis is -31.78 kcal/mol -30.41 -27.6 These molecules, therefore, can serve therapeutic molecules biomarkers research stress-impacted disorders. While offering implications disorders attenuating impact, it emphasize that ligands’ transition clinical applications necessitates extensive experimental research, including trials, unravel intricate neural pathways involved interactions.

Language: Английский

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(+)-catechin protects PC12 cells against CORT-induced oxidative stress and pyroptosis through the pathways of PI3K/AKT and Nrf2/HO-1/NF-κB

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 28, 2024

Pyroptosis induced by oxidative stress is a significant contributor to mental health disorders, including depression (+)-Catechin (CA), polyphenolic compound prevalent in various food sources, has been substantiated prior research exhibit potent antioxidant properties and potential antidepressant effects. Nonetheless, the precise antidepressive mechanisms effects of CA remain incompletely elucidated. In this study, we employed corticosterone (CORT) PC12 cells develop cellular model depression, aiming investigate protective against CORT-induced damage. Our objective was elucidate underlying action. We utilized transcriptomic analysis identify differentially expressed genes bioinformatics approaches predict CA’s cells. These predictions were subsequently validated through western blot analysis. The findings indicated that possesses capacity mitigate suppress pyroptosis via activation PI3K/AKT signaling pathway. This modulates Nrf2/HO1/NF-κB pathways, thereby providing protection damage CORT. Furthermore, investigated interaction between Keap1 protein employing molecular docking thermal shift assays. propose can activate Nrf2 two decrease reactive oxygen species (ROS) levels inhibit pyroptosis: one mechanism involves pathway, other direct binding Keap1, leading an increase p-Nrf2.

Language: Английский

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Unveiling the neuroprotection effects of Volvalerenic acid A: Mitochondrial fusion induction via IDO1-mediated Stat3-Opa1 signaling pathway

Phytomedicine, Journal Year: 2024, Volume and Issue: 129, P. 155555 - 155555

Published: March 20, 2024

Language: Английский

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SARS-CoV-2 Infection and Alpha-Synucleinopathies: Potential Links and Underlying Mechanisms

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12079 - 12079

Published: Nov. 10, 2024

Alpha-synuclein (α-syn) is a 140-amino-acid, intrinsically disordered, soluble protein that abundantly present in the brain. It plays crucial role maintaining cellular structures and organelle functions, particularly supporting synaptic plasticity regulating neurotransmitter turnover. However, for reasons not yet fully understood, α-syn can lose its physiological begin to aggregate. This altered disrupts dopaminergic transmission causes both presynaptic postsynaptic dysfunction, ultimately leading cell death. A group of neurodegenerative diseases known as α-synucleinopathies characterized by intracellular accumulation deposits specific neuronal glial cells within certain brain regions. In addition Parkinson's disease (PD), these conditions include dementia with Lewy bodies (DLBs), multiple system atrophy (MSA), pure autonomic failure (PAF), REM sleep behavior disorder (RBD). Given disorders are associated α-syn-related neuroinflammation-and considering SARS-CoV-2 infection has been shown affect nervous system, COVID-19 patients experiencing neurological symptoms-it proposed may contribute neurodegeneration PD other promoting misfolding aggregation. this review, we focus on whether could act an environmental trigger facilitates onset or progression α-synucleinopathies. Specifically, new evidence potential modulating function discuss causal relationship between development parkinsonism-like symptoms.

Language: Английский

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Salidroside and exercise performance in healthy active young adults – an exploratory, randomized, double-blind, placebo-controlled study

Journal of the International Society of Sports Nutrition, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 27, 2024

Background Rhodiola rosea extract is purported to improve physical performance and support resilience stress. Salidroside considered be one of the main constituents responsible for ergogenic actions R. rosea. However, contains relatively little salidroside cultivation challenging as it mainly found in high-altitude, cold regions. Additionally, plant subject conservation concerns because its growing popularity. The purpose this exploratory study was evaluate short-term effects pure, biosynthetic supplementation on exercise performance, mood state, markers inflammation muscle damage healthy active young adults.

Language: Английский

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Editorial: Exploring the key targets and compounds that manipulate brain neurocircuits against mental disorders and psychiatric

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 29, 2024

Language: Английский

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Research progress on anti-cancer mechanism of salidroside regulating miRNA-mRNA signaling axis

ONCOLOGIE, Journal Year: 2024, Volume and Issue: 26(4), P. 525 - 534

Published: July 1, 2024

Language: Английский

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