scholarly journals A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington’s disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254834
Author(s):  
Rodrigo Pérez-Arancibia ◽  
Jose Luis Ordoñez ◽  
Alexis Rivas ◽  
Philippe Pihán ◽  
Alfredo Sagredo ◽  
...  

Accumulation of misfolded proteins in the brain is a common hallmark of most age-related neurodegenerative diseases. Previous studies from our group identified the presence of anti-inflammatory and antioxidant compounds in leaves derived from the Chilean berry Ugni molinae (murtilla), in addition to show a potent anti-aggregation activity in models of Alzheimer´s disease. However, possible beneficial effects of berry extracts of murtilla was not investigated. Here we evaluated the efficacy of fruit extracts from different genotypes of Chilean-native U. molinae on reducing protein aggregation using cellular models of Huntington´s disease and assess the correlation with their chemical composition. Berry extraction was performed by exhaustive maceration with increasing-polarity solvents. An unbiased automatic microscopy platform was used for cytotoxicity and protein aggregation studies in HEK293 cells using polyglutamine-EGFP fusion proteins, followed by secondary validation using biochemical assays. Phenolic-rich extracts from murtilla berries of the 19–1 genotype (ETE 19–1) significantly reduced polyglutamine peptide aggregation levels, correlating with the modulation in the expression levels of autophagy-related proteins. Using LC-MS and molecular network analysis we correlated the presence of flavonoids, phenolic acids, and ellagitannins with the protective effects of ETE 19–1 effects on protein aggregation. Overall, our results indicate the presence of bioactive components in ethanolic extracts from U. molinae berries that reduce the load of protein aggregates in living cells.

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Munehiro Kitada ◽  
Daisuke Koya

Resveratrol (3,5,4′-trihydroxystilbene), a natural polyphenolic compound found in grapes and red wine, is reported to have beneficial effects on cardiovascular diseases, including renal diseases. These beneficial effects are thought to be due to this compound’s antioxidative properties: resveratrol is known to be a robust scavenger of reactive oxygen species (ROS). In addition to scavenging ROS, resveratrol may have numerous protective effects against age-related disorders, including renal diseases, through the activation of SIRT1. SIRT1, an NAD+-dependent deacetylase, was identified as one of the molecules through which calorie restriction extends the lifespan or delays age-related diseases, and this protein may regulate multiple cellular functions, including apoptosis, mitochondrial biogenesis, inflammation, glucose/lipid metabolism, autophagy, and adaptations to cellular stress, through the deacetylation of target proteins. Previous reports have shown that resveratrol can ameliorate several types of renal injury, such as diabetic nephropathy, drug-induced injury, aldosterone-induced injury, ischemia-reperfusion injury, sepsis-related injury, and unilateral ureteral obstruction, in animal models through its antioxidant effect or SIRT1 activation. Therefore, resveratrol may be a useful supplemental treatment for preventing renal injury.


2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Gizem Donmez

Sirtuins are highly conserved NAD+-dependent enzymes that were shown to have beneficial effects against age-related diseases. Aging is the major risk factor for all neurodegenerative disorders including Alzheimer’s Disease (AD). Sirtuins have been widely studied in the context of AD using different mouse models. In most of these studies, overexpression of SIRT1 has been shown to have protective effects against AD. Therefore, designing therapeutics based on increasing SIRT1 activity might be important for investigating the ways of treatment for this disease. This paper summarizes the recent research on the effect of SIRT1 in AD animal models and also the potential of SIRT1 being a therapeutical target for AD.


2018 ◽  
Vol 24 (3) ◽  
pp. 365-378 ◽  
Author(s):  
Chen Guang-Yi ◽  
Ge Li-Sha ◽  
Li Yue-Chun

The morbidity of myocarditis demonstrates an upward tendency by years, is commonly defined as the inflammation of myocytes and is caused by multiple factors. With the development of the molecular biological technique, great breakthroughs in the diagnosis and understanding of pathophysiological mechanisms of myocarditis have recently been achieved. Several questions remain unresolved, however, including standard treatment approaches to myocarditis, which remain controversial and ambiguous. Heart rate, as an independent risk factor, has been shown to be related to cardiac disease. Recent studies also show that the autonomic nervous system is involved in immunomodulatory myocarditis processes. Heart rate reduction treatment is recommended in myocarditis based on a number of animal experiments and clinical trials. It is possible that heart rate-lowering treatments can help to attenuate the inflammatory response and myocyte injury and reverse ventricular remodeling. However, how to execute the protective effects of heart rate reduction on myocarditis is still not clear. In this review, we discuss the pathogenesis and pathophysiological process of viral myocarditis and propose heart rate lowering as a therapeutic target for myocarditis, especially in light of the third-generation β-blockade carvedilol and funny channel blocker ivabradine. We also highlight some additional beneficial effects of such heart rate reduction agents, including anti-inflammatory, antioxidation, anti-nitrosative stress, anti-fibrosis and antiapoptosis properties.


Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mercedes M. Pérez-Jiménez ◽  
José M. Monje-Moreno ◽  
Ana María Brokate-Llanos ◽  
Mónica Venegas-Calerón ◽  
Alicia Sánchez-García ◽  
...  

AbstractAging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer’s disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.


2018 ◽  
Vol 19 (8) ◽  
pp. 2180 ◽  
Author(s):  
María Ariza ◽  
Tamara Forbes-Hernández ◽  
Patricia Reboredo-Rodríguez ◽  
Sadia Afrin ◽  
Massimiliano Gasparrini ◽  
...  

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.


2014 ◽  
pp. 309 ◽  
Author(s):  
Cristovam Picanço-Diniz ◽  
Thais Cristina Galdino De Oliveira ◽  
Fernanda Cabral Soares ◽  
Liliane Dias E Dias De Macedo ◽  
Domingos Luiz Wanderley Picanco Diniz ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 936-936
Author(s):  
Juliet Sobering ◽  
Lisa Brown

Abstract Older adults are vulnerable to particular risk factors that contribute to lower well-being and poorer functioning. With the COVID-19 pandemic, the importance of social support has been highlighted in media reports because of its well-known beneficial effects on overall well-being. However, as adults age, social networks, contacts, and activities naturally decrease. These age-related losses are often difficult, if not impossible, to replace. Pets have recently been recognized as a valuable source of social support for many older adults, providing both physical and psychological benefits through mutual connection and behavioral activation. Previous studies have examined how human social support or pet social support enhance older adults’ well-being (i.e., positive emotions, engagement, relationships, accomplishment, and meaning). However, there is a gap in our scientific knowledge as previous research has not evaluated if pet social support can serve as a protective factor in the absence of adequate human social support. Current analyses, with 141 older adult participants, suggests that pet owners with a positive attachment to their pet experience higher well-being as pets serve as a coping resource that protects against common life stressors. Similar to human social support, pet social support appears to be a protective factor that also promotes and fosters a sense of well-being in older adults. Support in late life is especially important for families and agencies to be attuned to, especially during a global pandemic.


2021 ◽  
Vol 14 (4) ◽  
pp. 310
Author(s):  
Ana V. González-de-Peredo ◽  
Mercedes Vázquez-Espinosa ◽  
Ceferino Carrera ◽  
Estrella Espada-Bellido ◽  
Marta Ferreiro-González ◽  
...  

Onion, one of the most consumed vegetables in the world, is also known to contain high levels of antioxidant compounds, with protective effects against different degenerative pathologies. Specifically, onion is rich in flavonols, mainly quercetin derivatives, which are compounds with high antioxidant and free radical scavenging power. For this reason, it is of the utmost importance to count on optimal analytical methods that allow for the determination and quantification of these compounds of interest. A rapid ultra-high performance liquid chromatography (UHPLC)-photo-diode array (PDA) method for the separation of the major flavonols in onions was developed using a Box–Behnken design in conjunction with multiresponse optimization on the basis of the desirability function. The conditions that provided a successful separation were 9.9% and 53.2% of phase B at the beginning and at the end of the gradient, respectively; 55 °C column working temperature; and 0.6 mL min−1 flow rate. The complete separation was achieved in less than 2.7 min with excellent chromatographic characteristics. The method was validated, and its high precision, low detection and quantification limits, good linearity, and robustness were confirmed. The correct applicability of the method improves the analysis of the raw material, increasing the quality of onions and its subproducts in terms of bioactive compounds and functional characteristics for consumers.


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