Neuroprotective efficacy of berberine and caffeine against rotenone‐induced neuroinflammatory and oxidative disturbances associated with Parkinson’s disease via inhibiting α-synuclein aggregation and boosting dopamine release

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

Abstract Parkinson's disease (PD) is characterized by motor impairment, glial-mediated inflammation, redox imbalance, and α-synuclein (α-syn) aggregation. Conventional therapies relieve early PD symptoms, but they do not repair dopaminergic neurons. Berberine (BBR) caffeine (CAF), both natural alkaloids, exhibited neuroprotective effects in many neurodegenerative disorders. Consequently, we hypothesized that the combination of BBR CAF would offer protection against PD-related impairments rotenone (ROT)-induced rat model when compared to commercial drug, metformin (MTF). Our results showed combined administration (25 mg/kg/day) (2.5 for four weeks prevented deficits, weight reduction, dopamine (DA) depletion, monoamine oxidase (MAO) activity ROT-induced rats comparison with monotherapy along MTF. This produced a notable effect reducing tumor necrosis factor (TNF)-α interleukin-16 (IL-6) midbrain rats. combinations markedly normalized tyrosine hydroxylase (TH) levels decreased total α-syn α-syn-p ser129 aggregation increased protein phosphatase 2A (PP2A) levels. Histological analysis indicated damaged neurons significant amelioration co-administration CAF. The molecular docking had binding affinity pocket surrounding α-syn, PP2A, TH They are predicted serve as effective inhibitors enzyme-mediated phosphorylation α-syn- pser129 . Conclusively, presents novel strategy neuroprotection blocking initial events incidence, demonstrating considerable anti-oxidative anti-inflammatory benefits relative Graphical abstract

Language: Английский

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Overview of Metformin and Neurodegeneration: A Comprehensive Review

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 486 - 486

Published: March 28, 2025

This comprehensive review examines the therapeutic potential of metformin, a well-established diabetes medication, in treating neurodegenerative disorders. Originally used as first-line treatment for type 2 diabetes, recent studies have begun investigating metformin’s effects beyond metabolic disorders, particularly its neuroprotective capabilities against conditions like Parkinson’s disease, Alzheimer’s Huntington’s and multiple sclerosis. Key findings demonstrate that operate through pathways: AMPK activation enhancing cellular energy metabolism autophagy; upregulation antioxidant defenses; suppression inflammation; inhibition protein aggregation; improvement mitochondrial function. These mechanisms collectively address common pathological features neurodegeneration neuroinflammation, including oxidative stress, accumulation, dysfunction. Clinical preclinical evidence supporting association with improved cognitive performance, reduced risk dementia, modulation hallmarks diseases is critically evaluated. While metformin shows promise agent, this emphasizes need further investigation to fully understand optimal applications diseases.

Language: Английский

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Diabetes and dementia: current data

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Journal Year: 2025, Volume and Issue: 21(2), P. 215 - 225

Published: April 1, 2025

This review analyzes current data on the epidemiology, pathogenesis, clinical features, and approaches to treatment of cognitive impairments in diabetes mellitus (DM). DM is recognized as an independent risk factor for dementia, particularly Alzheimer’s disease vascular increasing their likelihood by 50–91 %. The mechanism disorders includes brain insulin resistance, hyperglycemia, beta-amyloid accumulation, tau pathology, oxidative stress, dysfunction, neuroinflammation. Insulin resistance disrupts signaling pathways (IRS-1/PI3K/AKT), contributing neurodegeneration, while chronic hyperglycemia damages endothelium, accelerates atherosclerosis, increases dementia due ischemic neuronal damage. According guidelines, impairment screening recommended all individuals with over 65 years old (earlier if mental changes are observed) using psychodiagnostic tests. Diagnosis also neuroimaging, cerebral hemodynamics analysis, cerebrospinal fluid biomarker testing (beta-amyloid, protein), PET scans amyloid tau, along damage markers, promising early detection staging disease. Treatment strategies should be individualized, focusing glycemic control (target HbA1c < 8.0 % elderly), minimizing hypo-/hyperglycemia, preventing complications. Dementia involves combining antidiabetic therapy standard approaches: cholinesterase inhibitors, NMDA receptor antagonists, or anti-amyloid monoclonal antibodies. strategy aims slow decline improve patient quality life. Metformin, a pathogenetically relevant drug, plays key role not only but treatment, it reduces burden, suppresses inflammation, activates AMPK pathway, stimulates neurogenesis, improves function even non-diabetic patients. Long-term metformin use associated 29–84 reduced depending duration, its combination other drugs may provide synergy slowing neurodegeneration. prevention lifestyle modifications (physical activity, healthy diet), correction harmful habits, avoiding environmental risks, controlling body weight, blood pressure, lipid levels.

Language: Английский

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The Janus Face of Astrocytes in Multiple Sclerosis: Balancing Protection and Pathology

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111356 - 111356

Published: April 1, 2025

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and neurodegeneration in the central nervous system (CNS), predominantly affecting young adults with notable female predominance. While pathogenesis of MS involves complex interactions between peripheral immune cells CNS glia, astrocytes-the most abundant glial cells-play dual role disease progression. Traditionally classified into pro-inflammatory A1 neuroprotective A2 phenotypes, recent single-cell spatial transcriptomics reveal that human astrocytes exhibit continuum states beyond this binary paradigm. In MS, reactive contribute to neurotoxicity disrupting blood-brain barrier (BBB), promoting glutamate excitotoxicity, presenting antigens autoreactive T cells. Conversely, they also support repair through neurotrophic factor release (e.g., BDNF, CNTF) remyelination. Emerging therapies like dimethyl fumarate (DMF) fingolimod modulate astrocyte reactivity, targeting oxidative stress sphingosine-1-phosphate receptors mitigate neuroinflammation. However, challenges persist translating murine A1/A2 concepts as display heterogeneous, context-dependent responses influenced regional microenvironments stages. Advanced techniques, including multi-omics, highlight astrocyte-microglia crosstalk metabolic reprogramming key drivers pathology. This review synthesizes current evidence on heterogeneity, their Janus-faced roles therapeutic potential astrocyte-targeted strategies, advocating for precision approaches account human-specific biology. Future research must priorities human-centric biomarkers dynamic modelling bridge gap experimental findings clinical applications.

Language: Английский

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THE IMPACT OF METFORMIN USE ON RISK, PROGRESSION, AND SEVERITY OF DEMENTIA: A SYSTEMATIC REVIEW

Published: July 5, 2024

This study aimed to investigate the impact of metformin use on risk, progression, and severity dementia, considering its potential neuroprotective effects. Through a comprehensive literature review analysis epidemiological studies, clinical trials, comparative research, we synthesized evidence evaluate relationship between therapy dementia outcomes. Our findings revealed conflicting perspectives, with some studies suggesting protective effect in reducing while others indicated mixed results regarding influence cognitive function disease progression diagnosed patients. Despite these discrepancies, our underscores importance personalized approaches need for further particularly large-scale, long-term randomized controlled clarify therapeutic optimize practice context management.

Language: Английский

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