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1.
Cell Physiol Biochem ; 58(5): 548-570, 2024 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-39370950

RESUMO

BACKGROUND/AIMS: High Monomeric Polyphenols Berries Extract (HMPBE) is a formula highly rich in polyphenols clinically proven to enhance learning and memory. It is currently used to enhances cognitive performance including accuracy, working memory and concentration. METHODS: Here, we investigated for the first time the beneficial effects of HMPBE in a mouse model of acute and chronic traumatic brain injury (TBI). RESULTS: HMPBE, at the dose of 15 mg/kg was able to reduce histological alteration as well as inflammation and lipid peroxidation. HMPBE ameliorate TBI by improving Nrf-2 pathway, reducing Nf-kb nuclear translocation and apoptosis, and ameliorating behavioral alteration such as anxiety and depression. Moreover, in the chronic model of TBI, HMPBE administration restored the decline of Tyrosine Hydroxylase (TH) and dopamine transporter (DAT) and the accumulation of a-synuclein into the midbrain region. This finding correlates the beneficial effect of HMPBE administration with the onset of parkinsonism related to traumatic brain damage. CONCLUSION: The data may open a window for developing new support strategies to limit the neuroinflammation event of acute and chronic TBI.


Assuntos
Frutas , Fator 2 Relacionado a NF-E2 , NF-kappa B , Extratos Vegetais , Polifenóis , Proteína X Associada a bcl-2 , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Polifenóis/farmacologia , Polifenóis/química , Polifenóis/uso terapêutico , Camundongos , NF-kappa B/metabolismo , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Frutas/química , Proteína X Associada a bcl-2/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/patologia , Modelos Animais de Doenças , Tirosina 3-Mono-Oxigenase/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Peroxidação de Lipídeos/efeitos dos fármacos
2.
Int J Exp Pathol ; 2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39397270

RESUMO

Metabolic syndrome (MetS) is becoming an increasing public health challenge. Many of the individual components of MetS are associated with ocular changes, but it is not yet clear what the association is. It is known that MetS can lead to diabetes and hence its consequences such as retinopathy. Osteopontin (OPN) is a phosphoglycoprotein that appears to be implicated in diabetic retinopathy. Given the involvement of OPN in retinal damage, the aim of this research was to evaluate OPN expression and its variation over time in a model of MetS induced by 30% fructose consumption for 1, 2 and 3 months. The weight of the animals and the consumption of food and fructose/water were evaluated during the experiment. The results showed a time-dependent increase in weight and liquid consumption in animals treated with fructose, while there was no significant difference in food consumption. Subsequently, the biochemical parameters confirmed that the animals treated with fructose, over time, underwent alterations like those found in patients with MetS. We then moved on to the evaluation of OPN and microglia. In both cases, we observed a time-dependent increase in OPN and Iba-1 in fructose consumption. Furthermore, the results showed a gradual loss of ZO-1 and occludin levels over time. Thus identification of OPN in patients with MetS could be used as an early marker of retinal damage, and this could help to prevent the complications related to the progression of this pathology.

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5.
Mech Ageing Dev ; 220: 111960, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38971236

RESUMO

Neurodegenerative diseases have multifactorial pathogenesis, mainly involving neuroinflammatory processes. Finding drugs able to treat these diseases, expecially because for most of these diseases there are no effective drugs, and the current drugs cause undesired side effects, represent a crucial point. Most in vivo and in vitro studies have been concentrated on various aspects related to neurons (e.g. neuroprotection), however, there has not been focus on the prevention of early stages involving glial cell activation and neuroinflammation. Recently, it has been demonstrated that nutritional phytochemicals including polyphenols, the main active constituents of the Mediterranean diet, maintain redox balance and neuroprotection through the activation of hormetic vitagene pathway. Recent lipidomics data from our laboratory indicate mushrooms as strong nutritional neuronutrients with strongly activity against neuroinflammation in Meniere' diseaseas, a model of cochleovestibular neural degeneration, as well as in animal model of traumatic brain injury, or rotenone induced parkinson's disease. Moreover, Hidrox®, an aqueous extract of olive containing hydroxytyrosol, and Boswellia, acting as Nrf2 activators, promote resilience by enhancing the redox potential, and thus, regulate through hormetic mechanisms, cellular stress response mechanisms., Thus, modulation of cellular stress pathways, in particular vitagenes system, may be an innovative approach for therapeutic intervention in neurodegenerative disorders.


Assuntos
Hormese , Humanos , Animais , Envelhecimento Saudável/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico
7.
Arch Biochem Biophys ; 758: 110083, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38969196

RESUMO

Fibromyalgia (FMS) is a persistent syndrome marked by widespread musculoskeletal pain and behavioural symptoms. Given the hypothesis linking FMS aetiology to mitochondrial dysfunction and oxidative stress, we examined the biochemical correlation among these factors by studying specific proteins associated with mitochondrial homeostasis in muscle. Additionally, this study investigated the role of Boswellia serrata gum resin extract (BS), known for its various functions, including the potent induction of antioxidant enzymes, in determining protective or reparative mechanisms in the muscle cells. Sprague-Dawley rats were injected with reserpine to induce FMS. These animals exhibited moderate changes in hind limb skeletal muscles, experiencing mobility difficulties. Additionally, there were noteworthy morphological and ultrastructural alterations, along with the expression of myogenin, mitochondrial enzymes and oxidative stress markers in the gastrocnemius muscle. Interestingly, BS demonstrated a reduction in spontaneous motor activity difficulties. Moreover, BS showed a positive impact on musculoskeletal morphostructural aspects, as well as a decrease in oxidative stress and mitochondrial alterations. In particular, BS restored the mRNA expression of citrate synthase and cytochrome-c oxidase subunit II and the activity of electron transfer chain complexes. BS also influenced mitochondrial biogenesis, upregulating PGC-1α expression and the related transcription factors (Nrf1, Tfam, Nrf2, FOXO3a, SIRT3, GCLC, NQO1, SOD2 and GPx4), oxidative stress (lipid peroxidation, GSH levels and GSH-Px activity) and mitochondrial dynamics and function (Mnf2 expression and CoQ10 levels). Overall, this study underlined the key role of the mitochondrial alteration in FMS and that BS had a very high antioxidant effect in these organelles and also in the cells.


Assuntos
Fibromialgia , Músculo Esquelético , Estresse Oxidativo , Ratos Sprague-Dawley , Fibromialgia/metabolismo , Fibromialgia/induzido quimicamente , Fibromialgia/patologia , Animais , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Ratos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/patologia , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Antioxidantes/metabolismo
9.
Environ Toxicol Pharmacol ; 109: 104496, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38959819

RESUMO

Endocrine disruptors (EDs) pose significant risks to human and environmental health, with potential implications for neurotoxicity. This study investigates the synergistic neurotoxic effects of perfluorooctane sulfonate (PFOS) and glyphosate (GLY), two ubiquitous EDs, using SHSY5Y neuronal and C6 astrocytic cell lines. While individual exposures to PFOS and glyphosate at non-toxic concentrations did not induce significant changes, their combination resulted in a marked increase in oxidative stress and neuroinflammatory responses. Specifically, the co-exposure led to elevated levels of interleukin-6, tumor necrosis factor alpha, and interferon gamma, along with reduced interleukin-10 expression, indicative of heightened neuroinflammatory processes. These findings underscore the importance of considering the synergistic interactions of EDs in assessing neurotoxic risks and highlight the urgent need for further research to mitigate the adverse effects of these compounds on neurological health.


Assuntos
Ácidos Alcanossulfônicos , Disruptores Endócrinos , Fluorocarbonos , Glicina , Glifosato , Glicina/análogos & derivados , Glicina/toxicidade , Fluorocarbonos/toxicidade , Disruptores Endócrinos/toxicidade , Humanos , Ácidos Alcanossulfônicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular Tumoral , Linhagem Celular , Animais , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Herbicidas/toxicidade , Citocinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ratos
10.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167301, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-38878832

RESUMO

A critical role for mitochondrial dysfunction has been shown in the pathogenesis of fibromyalgia. It is a chronic pain syndrome characterized by neuroinflammation and impaired oxidative balance in the central nervous system. Boswellia serrata (BS), a natural polyphenol, is a well-known able to influence the mitochondrial metabolism. The objective of this study was to evaluate the mitochondrial dysfunction and biogenesis in fibromyalgia and their modulation by BS. To induce the model reserpine (1 mg/Kg) was subcutaneously administered for three consecutive days and BS (100 mg/Kg) was given orally for twenty-one days. BS reduced pain like behaviors in reserpine-injected rats and the astrocytes activation in the dorsal horn of the spinal cord and prefrontal cortex that are recognized as key regions associated with the neuropathic pain. Vulnerability to neuroinflammation and impaired neuronal plasticity have been described as consequences of mitochondrial dysfunction. BS administration increased PGC-1α expression in the nucleus of spinal cord and brain tissues, promoting the expression of regulatory genes for mitochondrial biogenesis (NRF-1, Tfam and UCP2) and cellular antioxidant defence mechanisms (catalase, SOD2 and Prdx 3). According with these data BS reduced lipid peroxidation and the GSSG/GSH ratio and increased SOD activity in the same tissues. Our results also showed that BS administration mitigates cytochrome-c leakage by promoting mitochondrial function and supported the movement of PGC-1α protein into the nucleus restoring the quality control of mitochondria. Additionally, BS reduced Drp1 and Fis1, preventing both mitochondrial fission and cell death, and increased the expression of Mfn2 protein, facilitating mitochondrial fusion. Overall, our results showed important mitochondrial dysfunction in central nervous system in fibromyalgia syndrome and the role of BS in restoring mitochondrial dynamics.


Assuntos
Fibromialgia , Mitocôndrias , Fibromialgia/metabolismo , Fibromialgia/patologia , Animais , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Ratos , Masculino , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Biogênese de Organelas , Medula Espinal/metabolismo , Medula Espinal/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Extratos Vegetais/farmacologia , Modelos Animais de Doenças
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