Age specific neuroprotection of curcumin is through differential modulation of brain dopamine metabolism: Insights from Drosophila model of Parkinson’s disease DOI Creative Commons

Mohamad Ayajuddin,

Abhik Das, Sarat Chandra Yenisetti

et al.

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

Published: July 27, 2024

Abstract Epidemiological studies suggest a strong linkage between exposure to environmental toxins and onset of Parkinson’s disease (PD). Rotenone is widely used pesticide known inhibitor mitochondrial complex I, that has been shown induce Parkinsonian phenotypes in various animal models. Our laboratory developed rotenone mediated ALSS Drosophila model PD which critical screen small molecules identify molecular targets dopaminergic neuroprotection for late-onset neurodegenerative diseases such as PD. Using negative geotaxis assay, qualitative quantitative analysis neurons by fluorescence microscopy further quantifying the levels dopamine its metabolites HPLC, we have assessed neurodegeneration under induced conditions employing curcumin Exposure induces mobility defects health transition phase adult Drosophila; whereas ameliorates deficits only during early but fail late phases. Probing whole fly brain using anti-tyrosine hydroxylase antibodies, illustrates it does not cause loss per se. However, leads “neuronal dysfunction” (diminished rate limiting enzyme synthesis) rescues neuronal dysfunction fails mitigate pathology life. Genotropic nutraceutical replenishes diminished specific DOPAC HVA do so phase, suggesting life phase-specific neuroprotective efficacy through differential modulation perturbations metabolism. Present study suggests limitation therapeutic agent emphasizes necessity screening putative matched models sets in.

Language: Английский

Targeting natural antioxidant polyphenols to protect neuroinflammation and neurodegenerative diseases: a comprehensive review DOI Creative Commons
Maroua Jalouli, Md. Ataur Rahman, Partha Biswas

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 24, 2025

Polyphenols, naturally occurring phytonutrients found in plant-based foods, have attracted significant attention for their potential therapeutic effects neurological diseases and neuroinflammation. These compounds possess diverse neuroprotective capabilities, including antioxidant, anti-inflammatory, anti-amyloid properties, which contribute to mitigating the progression of neurodegenerative conditions such as Alzheimer's Disease (AD), Parkinson's (PD), Dementia, Multiple Sclerosis (MS), Stroke, Huntington's (HD). Polyphenols been extensively studied ability regulate inflammatory responses by modulating activity pro-inflammatory genes influencing signal transduction pathways, thereby reducing neuroinflammation neuronal death. Additionally, polyphenols shown promise various cellular signaling pathways associated with viability, synaptic plasticity, cognitive function. Epidemiological clinical studies highlight polyphenol-rich diets decrease risk alleviate symptoms disorders Furthermore, demonstrated through regulation key Akt, Nrf2, STAT, MAPK, play critical roles neuroprotection body's immune response. This review emphasizes growing body evidence supporting combating neurodegeneration neuroinflammation, well enhancing brain health. Despite substantial promising hypotheses, further research investigations are necessary fully understand role establish them advanced targets age-related neuroinflammatory conditions.

Language: Английский

Citations

3
Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence DOI Open Access

Yandra Cervelim Nunes,

Nathalia. M. Mendes,

Enzo Pereira de Lima

et al.

Published: July 12, 2024

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant anti-inflammatory properties, has emerged as promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms curcumin's effects optimal dosages different conditions necessitate further investigation. This systematic review synthesizes current evidence on potential addressing disorders, emphasizing its impact cognitive function, neurodegeneration, muscle health older adults. By evaluating safety, efficacy, action curcumin supplementation, this aims provide insights into therapeutic promoting healthy aging. A search across three databases using specific keywords yielded 2,256 documents, leading selection 15 clinical trials synthesis. Here we highlight multifaceted agent combating disorders. The findings suggest that could offer effective approach enhancing quality life aging individuals. Further research well-designed are essential validate optimize use personalized medicine approaches conditions.

Language: Английский

Citations

8
Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence DOI Open Access

Yandra Cervelim Nunes,

Nathalia. M. Mendes,

Enzo Pereira de Lima

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(16), P. 2721 - 2721

Published: Aug. 15, 2024

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant anti-inflammatory properties, has emerged as promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms curcumin’s effects optimal dosages different conditions necessitate further investigation. This systematic review synthesizes current evidence on potential addressing disorders, emphasizing its impact cognitive function, neurodegeneration, muscle health older adults. By evaluating safety, efficacy, action curcumin supplementation, this aims provide insights into therapeutic promoting healthy aging. A search across three databases using specific keywords yielded 2256 documents, leading selection 15 clinical trials synthesis. Here, we highlight multifaceted agent combating disorders. The findings suggest that could offer effective approach enhancing quality life aging individuals. Further research well-designed are essential validate optimize use personalized medicine approaches conditions.

Language: Английский

Citations

8
Nitric Oxide in Parkinson’s Disease: The Potential Role of Dietary Nitrate in Enhancing Cognitive and Motor Health via the Nitrate–Nitrite–Nitric Oxide Pathway DOI Open Access
Gianluca Tripodi, Mauro Lombardo,

Sercan Kerav

et al.

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 393 - 393

Published: Jan. 22, 2025

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in substantia nigra pars compacta, leading to motor symptoms such as tremor, rigidity, and bradykinesia. The pathological hallmarks PD include Lewy bodies mechanisms like oxidative/nitrosative stress, chronic inflammation, mitochondrial dysfunction. Nitric oxide (NO), produced nitric synthase (NOS) isoforms, plays dual role neuroprotection neurodegeneration. Excessive NO production exacerbates neuroinflammation damage, contributing cell death. This review explores NO’s pathogenesis investigates dietary nitrate therapeutic strategy regulate levels. Methods: A literature studies addressing was conducted using major scientific databases, including PubMed, Scopus, Web Science, keywords “nitric oxide”, “NOSs”, “Parkinson’s disease”, “nitrate PD”. Studies on metabolism via nitrate–nitrite–NO pathway its effects were analyzed. regarding nitrosamine formation PD, which are mainly formed during nitrification process amines (nitrogen-containing compounds), often due chemical reactions presence nitrite or nitrate, also examined. In particular, has been shown induce oxidative affect function, contribute inflammatory phenomena brain, another factor closely related PD. Results: production, particularly from iNOS nNOS, strongly associated with amplifying neuronal damage Dietary enhance bioavailability through pathway, mitigating inflammation damage. Conclusions: Dysregulated contributes significantly progression pathways. modulating levels, offers promising counteract these mechanisms. Further clinical trials warranted establish efficacy optimize use management.

Language: Английский

Citations

1
Nutrition: A non‐negligible factor in the pathogenesis and treatment of Alzheimer's disease DOI Creative Commons

Boye Wen,

Xiaodong Han,

Jin Gong

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract Alzheimer's disease (AD) is a degenerative characterized by progressive cognitive dysfunction. The strong link between nutrition and the occurrence progression of AD pathology has been well documented. Poor nutritional status accelerates progress potentially aggravating amyloid beta (Aβ) tau deposition, exacerbating oxidative stress response, modulating microbiota–gut–brain axis, disrupting blood–brain barrier function. advanced stage tends to lead malnutrition due impairments, sensory dysfunctions, brain atrophy, behavioral psychological symptoms dementia (BPSD). This, in turn, produces vicious cycle AD. This review discusses how factors deteriorate each other from early terminal stages AD, focusing on potential different levels factors, ranging micronutrients diet patterns. provides novel insights into reducing risk delaying its progression, improving prognosis. Highlights Two‐fifths cases worldwide have attributed modifiable factors. Up ≈26% community‐dwelling patients with are malnourished, compared 7%∼76% institutionalized patients. Undernutrition effects onset, prognosis through multiple mechanisms. Various supports were confirmed be protective for via specific

Language: Английский

Citations

1
Protective effects of resveratrol against PM2.5-induced damage in hNSCs and its mitigation of PM2.5-induced mitochondrial dysfunction in a 3D scaffold system DOI
Ming‐Chang Chiang, Christopher J.B. Nicol, Yuping Yang

et al.

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

Published: Feb. 1, 2025

Language: Английский

Citations

1
Behavioral and Biochemical Insights into the Therapeutic Potential of Mitocurcumin in a Zebrafish–Pentylenetetrazole (PTZ) Epilepsy Model DOI Creative Commons

Alin Dumitru Ciubotaru,

Carmen-Ecaterina Leferman, Bogdan Ignat

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 382 - 382

Published: March 7, 2025

Background/Objectives: Epilepsy is a complex neurological disorder with strong link to oxidative stress, which contributes seizure susceptibility and neuronal damage. This study aims investigate the effects of curcumin (Cur), sodium valproate (VPA), mitocurcumin (MitoCur), mitochondria-targeted curcumin, on behavioral stress parameters in zebrafish model pentylenetetrazole (PTZ)-induced seizures. Methods: Adult were exposed two concentrations (0.25 0.5 µM for Cur MitoCur; 0.25 mM VPA). Behavioral assessments, including locomotion, spatial exploration, directional movement, conducted using EthoVision XT tracking software. Oxidative markers, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx), total antioxidant status (TAS), analyzed brain homogenates. Results: analyses indicated dose-dependent effects, higher doses generally reducing activity. MitoCur at enhanced defenses reduced damage, while exhibited pro-oxidant shift. VPA improved TAS without significantly altering MDA levels. Conclusions: These findings emphasize importance dose optimization antioxidant-based epilepsy treatments highlight potential as targeted therapeutic option.

Language: Английский

Citations

1
Mitochondrial Dysfunction in Endothelial Cells: A Key Driver of Organ Disorders and Aging DOI Creative Commons
Elena Grossini, Sakthipriyan Venkatesan, Mohammad Mostafa Ola Pour

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 372 - 372

Published: March 21, 2025

Mitochondria are of great importance in cell biology since they major sites adenosine triphosphate (ATP) production and widely involved different cellular pathways the response to stress. During ATP production, reactive oxygen species (ROS) can be produced. While a small amount ROS may important for regulation physiological processes, at elevated levels turn into harmful agents leading damage. From pathological perspective, it could particularly interesting focus on mitochondrial function endothelial cells development aging onset diseases, including renal, cardio-metabolic, liver neurodegenerative ones. However, date, there no surveys which address above issues. To fill this gap, valuable collect recent findings about role mitochondria function, not only increase knowledge but also clinical applications. Here, we overview most issues view characterizing as an innovative potential target prevention aging, well treatment conditions.

Language: Английский

Citations

1
Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders DOI
Mahan Farzan,

Behnaz Abedi,

Iman Bhia

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(16), P. 2966 - 2981

Published: July 31, 2024

Sinapic acid (SA) is a phenylpropanoid derivative found in various natural sources that exhibits remarkable versatile properties, including antioxidant, anti-inflammatory, and metal-chelating capabilities, establishing itself as promising candidate for the prevention treatment of conditions affecting central nervous system, such Alzheimer's disease (AD), Parkinson's (PD), ischemic stroke, other neurological disorders. These effects also include neuroprotection epilepsy models, evidenced by reduction seizure-like behavior, cell death specific hippocampal regions, lowered neuroinflammatory markers. In AD, SA enhances memory, reverses cognitive deficits, attenuates astrocyte activation. has positive on cognition improving memory lowering oxidative stress. This shown lower levels stress markers, higher antioxidant enzyme activity, better retention. Additionally, stroke PD provides microglial protection exerts anti-inflammatory effects. review emphasizes SA's multifaceted neuroprotective properties its potential role brain Despite need further research to fully understand mechanisms action clinical applicability, stands out valuable bioactive compound ongoing quest combat neurodegenerative diseases enhance quality life affected individuals.

Language: Английский

Citations

5
New Insights in Natural Bioactive Compounds for Periodontal Disease: Advanced Molecular Mechanisms and Therapeutic Potential DOI Creative Commons
Nada Tawfig Hashim, Rasha Babiker, Nallan CSK Chaitanya

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 807 - 807

Published: Feb. 10, 2025

Periodontal disease is a chronic inflammatory condition that destroys the tooth-supporting structures due to host's immune response microbial biofilms. Traditional periodontal treatments, such as scaling and root planing, pharmacological interventions, surgical procedures, have significant limitations, including difficulty accessing deep pockets, biofilm recolonization, development of antibiotic resistance. In light these challenges, natural bioactive compounds derived from plants, herbs, other sources offer promising alternative their anti-inflammatory, antioxidant, antimicrobial, tissue-regenerative properties. This review focuses on molecular mechanisms through which compounds, curcumin, resveratrol, epigallocatechin gallate (EGCG), baicalin, carvacrol, berberine, essential oils, Gum Arabic, exert therapeutic effects in disease. Bioactive inhibit critical pathways like NF-κB, JAK/STAT, MAPK while activating protective Nrf2/ARE, reducing cytokine production oxidative stress. They also activity matrix metalloproteinases (MMPs), preventing tissue degradation promoting healing. addition, demonstrated potential disrupt bacterial biofilms by interfering with quorum sensing, targeting cell membranes, enhancing efficacy.Bioactive modulate system shifting balance pro-inflammatory anti-inflammatory responses efferocytosis, helps resolve inflammation supports regeneration. However, despite challenges related poor bioavailability, stability oral cavity, absence large-scale clinical trials need be addressed. Future strategies should prioritize advanced delivery systems nanoparticles hydrogels enhance bioavailability sustain release, alongside long-term studies assess human populations. Furthermore, combining traditional treatments could provide synergistic benefits managing aims explore disease, emphasizing action offering insights into integration conventional therapies for more comprehensive approach health.

Language: Английский

Citations

0