Trehalose, a natural disaccharide, reduces stroke occurrence in the stroke-prone spontaneously hypertensive rat

Forte, Maurizio; Marchitti, Simona; Cotugno, Maria; Nonno, Flavio Di; Stanzione, Rosita; Bianchi, Franca; Schirone, Leonardo; Schiavon, Sonia; Vecchio, Danièle; Sarto, Gianmarco; Scioli, Mariarosaria; Raffa, Salvatore; Relucenti, Michela; Torrisi, Maria Rosaria; Valenti, Valentina; Versaci, Francesco; Vecchione, Carmine; Volpe, Massimo; Frati, Giacomo; Rubattu, Speranza; Sciarretta, Sebastiano

doi:10.1016/j.phrs.2021.105875

Cited by 22 publications

(12 citation statements)

References 40 publications

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“…To support this concept and further validate the suitability of our rat model, we previously reported the significant protective effect of a Brassica oleracea sprout extract administration toward renal and cerebrovascular damage occurrence in JD-fed SHRSP [ 12 ]. Moreover, the administration of the natural disaccharide trehalose, present in different foods, led to a significant delay in renal damage and stroke occurrence in JD-fed SHRSP [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Citrus Bergamia Polyphenolic Fraction on Saline Load-Induced Injury in Primary Cerebral Endothelial Cells from the Stroke-Prone Spontaneously Hypertensive Rat Model

et al. 2023

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High salt load is a known noxious stimulus for vascular cells and a risk factor for cardiovascular diseases in both animal models and humans. The stroke-prone spontaneously hypertensive rat (SHRSP) accelerates stroke predisposition upon high-salt dietary feeding. We previously demonstrated that high salt load causes severe injury in primary cerebral endothelial cells isolated from SHRSP. This cellular model offers a unique opportunity to test the impact of substances toward the mechanisms underlying high-salt-induced vascular damage. We tested the effects of a bergamot polyphenolic fraction (BPF) on high-salt-induced injury in SHRSP cerebral endothelial cells. Cells were exposed to 20 mM NaCl for 72 h either in the absence or the presence of BPF. As a result, we confirmed that high salt load increased cellular ROS level, reduced viability, impaired angiogenesis, and caused mitochondrial dysfunction with a significant increase in mitochondrial oxidative stress. The addition of BPF reduced oxidative stress, rescued cell viability and angiogenesis, and recovered mitochondrial function with a significant decrease in mitochondrial oxidative stress. In conclusion, BPF counteracts the key molecular mechanisms underlying high-salt-induced endothelial cell damage. This natural antioxidant substance may represent a valuable adjuvant to treat vascular disorders.

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Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Citrus Bergamia Polyphenolic Fraction on Saline Load-Induced Injury in Primary Cerebral Endothelial Cells from the Stroke-Prone Spontaneously Hypertensive Rat Model

et al. 2023

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“…Mitophagy was evaluated by cytofluorimetric assessment of mitochondrial mass upon staining with MitoTracker Green (MTG-FM; Molecular Probes, Invitrogen; 50 nM for 30 min at 37 °C) [ 27 , 28 ] and by colocalization analysis of fluorescent probes MitoTracker Green and LysoTracker Red (see above for staining details). Fluorescence signals were acquired by ApoTome System connected with an Axiovert 200 inverted microscope (Zeiss, Oberkochen, Germany).…”

Section: Methodsmentioning

confidence: 99%

Atrial natriuretic peptide stimulates autophagy/mitophagy and improves mitochondrial function in chronic heart failure

Raffa

Forte

Gallo

et al. 2023

Cell. Mol. Life Sci.

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Mitochondrial dysfunction, causing increased reactive oxygen species (ROS) production, is a molecular feature of heart failure (HF). A defective antioxidant response and mitophagic flux were reported in circulating leucocytes of patients with chronic HF and reduced ejection fraction (HFrEF). Atrial natriuretic peptide (ANP) exerts many cardiac beneficial effects, including the ability to protect cardiomyocytes by promoting autophagy. We tested the impact of ANP on autophagy/mitophagy, altered mitochondrial structure and function and increased oxidative stress in HFrEF patients by both ex vivo and in vivo approaches. The ex vivo study included thirteen HFrEF patients whose peripheral blood mononuclear cells (PBMCs) were isolated and treated with αANP (10–11 M) for 4 h. The in vivo study included six HFrEF patients who received sacubitril/valsartan for two months. PBMCs were characterized before and after treatment. Both approaches analyzed mitochondrial structure and functionality. We found that levels of αANP increased upon sacubitril/valsartan, whereas levels of NT-proBNP decreased. Both the ex vivo direct exposure to αANP and the higher αANP level upon in vivo treatment with sacubitril/valsartan caused: (i) improvement of mitochondrial membrane potential; (ii) stimulation of the autophagic process; (iii) significant reduction of mitochondrial mass—index of mitophagy stimulation—and upregulation of mitophagy-related genes; (iv) reduction of mitochondrial damage with increased inner mitochondrial membrane (IMM)/outer mitochondrial membrane (OMM) index and reduced ROS generation. Herein we demonstrate that αANP stimulates both autophagy and mitophagy responses, counteracts mitochondrial dysfunction, and damages ultimately reducing mitochondrial oxidative stress generation in PBMCs from chronic HF patients. These properties were confirmed upon sacubitril/valsartan administration, a pivotal drug in HFrEF treatment.

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“…Over the last decades, autophagy activation emerged as a potential therapeutic and preventive strategy toward stroke in preclinical models ( Forte et al, 2020 ; Forte et al, 2021a ; Forte et al, 2021b ; Wang et al, 2021 ). In regard to stroke, autophagy is activated in response to IS in all brain cells present in the damaged area such as neurons, glial cells, and microvascular cells ( Perez-Alvarez et al, 2018 ).…”

Section: Role Of Autophagy In Strokementioning

confidence: 99%

“…SHRSP rats fed with a high salt stroke-permissive diet failed to activate autophagy/mitophagy at the cerebral level. Restoration of autophagy with the administration of different compounds, such as the synthetic peptide Tat-Beclin1, the natural disaccharide trehalose and nicotinamide mononucleotide, reduced stroke occurrence with a parallel improvement of mitochondrial function ( Forte et al, 2020 ; Forte et al, 2021b ). Of interest, reactivation of autophagy rescued endothelial dysfunction in both isolated cerebral endothelial cells and in mesenteric arteries of SHRSP.…”

Section: Protective Effect Of Autophagy In Animal Models Of Ismentioning

confidence: 99%

Role of autophagy in ischemic stroke: insights from animal models and preliminary evidence in the human disease

Stanzione,

Pietrangelo,

Cotugno

et al. 2024

Front. Cell Dev. Biol.

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Stroke represents a main cause of death and permanent disability worldwide. The molecular mechanisms underlying cerebral injury in response to the ischemic insults are not completely understood. In this article, we summarize recent evidence regarding the role of autophagy in the pathogenesis of ischemic stroke by reviewing data obtained in murine models of either transient or permanent middle cerebral artery occlusion, and in the stroke-prone spontaneously hypertensive rat. Few preliminary observational studies investigating the role of autophagy in subjects at high cerebrovascular risk and in cohorts of stroke patients were also reviewed. Autophagy plays a dual role in neuronal and vascular cells by exerting both protective and detrimental effects depending on its level, duration of stress and type of cells involved. Protective autophagy exerts adaptive mechanisms which reduce neuronal loss and promote survival. On the other hand, excessive activation of autophagy leads to neuronal cell death and increases brain injury. In conclusion, the evidence reviewed suggests that a proper manipulation of autophagy may represent an interesting strategy to either prevent or reduce brain ischemic injury.

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Trehalose, a natural disaccharide, reduces stroke occurrence in the stroke-prone spontaneously hypertensive rat

Cited by 22 publications

References 40 publications

Beneficial Effects of Citrus Bergamia Polyphenolic Fraction on Saline Load-Induced Injury in Primary Cerebral Endothelial Cells from the Stroke-Prone Spontaneously Hypertensive Rat Model

Beneficial Effects of Citrus Bergamia Polyphenolic Fraction on Saline Load-Induced Injury in Primary Cerebral Endothelial Cells from the Stroke-Prone Spontaneously Hypertensive Rat Model

Atrial natriuretic peptide stimulates autophagy/mitophagy and improves mitochondrial function in chronic heart failure

Role of autophagy in ischemic stroke: insights from animal models and preliminary evidence in the human disease

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