Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications

2007 ◽  
Vol 35 (5) ◽  
pp. 1156-1160 ◽  
Author(s):  
C. Alarcón de la Lastra ◽  
I. Villegas

Resveratrol (3,4′,5-trihydroxystilbene) is found in various plants, including grapes, berries and peanuts. It is also present in wines, especially red wines. During the last years, it has been the focus of numerous in vitro and in vivo studies investigating its biological attributes, which include mainly antioxidant and anti-inflammatory activities, anti-platelet aggregation effect, anti-atherogenic property, oestrogen-like growth-promoting effect, growth-inhibiting activity, immunomodulation and chemoprevention. In fact, recently, it has been demonstrated that the stilbene blocks the multistep process of carcinogenesis at various stages: tumour initiation, promotion and progression. More recent results provide interesting insights into the effect of this compound on the life span of yeasts and flies, implicating the potential of resveratrol as an anti-aging agent in treating age-related human diseases. Nevertheless, depending on the concentration of the phytoalexin and the cell type, it has also been shown that resveratrol can exhibit pro-oxidant properties, leading to oxidative breakage of cellular DNA in the presence of transition metal ions such as copper. Recently, it has been proposed that such a pro-oxidant action could be a common mechanism for anticancer and chemopreventive properties of plant polyphenols. The present paper is intended to provide the reader up-to-date information on the antioxidant and pro-oxidant properties of resveratrol and its clinical implications.

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2243 ◽  
Author(s):  
Ranjini Sankaranarayanan ◽  
D. Ramesh Kumar ◽  
Janki Patel ◽  
G. Jayarama Bhat

Despite decades of research to elucidate the cancer preventive mechanisms of aspirin and flavonoids, a consensus has not been reached on their specific modes of action. This inability to accurately pinpoint the mechanism involved is due to the failure to differentiate the primary targets from its associated downstream responses. This review is written in the context of the recent findings on the potential pathways involved in the prevention of colorectal cancers (CRC) by aspirin and flavonoids. Recent reports have demonstrated that the aspirin metabolites 2,3-dihydroxybenzoic acid (2,3-DHBA), 2,5-dihydroxybenzoic acid (2,5-DHBA) and the flavonoid metabolites 2,4,6-trihydroxybenzoic acid (2,4,6-THBA), 3,4-dihydroxybenzoic acid (3,4-DHBA) and 3,4,5-trihydroxybenzoic acid (3,4,5-THBA) were effective in inhibiting cancer cell growth in vitro. Limited in vivo studies also provide evidence that some of these hydroxybenzoic acids (HBAs) inhibit tumor growth in animal models. This raises the possibility that a common pathway involving HBAs may be responsible for the observed cancer preventive actions of aspirin and flavonoids. Since substantial amounts of aspirin and flavonoids are left unabsorbed in the intestinal lumen upon oral consumption, they may be subjected to degradation by the host and bacterial enzymes, generating simpler phenolic acids contributing to the prevention of CRC. Interestingly, these HBAs are also abundantly present in fruits and vegetables. Therefore, we suggest that the HBAs produced through microbial degradation of aspirin and flavonoids or those consumed through the diet may be common mediators of CRC prevention.


2013 ◽  
Vol 304 (7) ◽  
pp. R473-R487 ◽  
Author(s):  
Daniela Salvemini ◽  
Sangwon F. Kim ◽  
Vincenzo Mollace

The nitric oxide (NO) and cyclooxygenase (COX) pathways share a number of similarities. Nitric oxide is the mediator generated from the NO synthase (NOS) pathway, and COX converts arachidonic acid to prostaglandins, prostacyclin, and thromboxane A2. Two major forms of NOS and COX have been identified to date. The constitutive isoforms critically regulate several physiological states. The inducible isoforms are overexpressed during inflammation in a variety of cells, producing large amounts of NO and prostaglandins, which may underlie pathological processes. The cross-talk between the COX and NOS pathways was initially reported by Salvemini and colleagues in 1993, when they demonstrated in a series of in vitro and in vivo studies that NO activates the COX enzymes to produce increased amounts of prostaglandins. Those studies led to the concept that COX enzymes represent important endogenous “receptor” targets for amplifying or modulating the multifaceted roles of NO in physiology and pathology. Since then, numerous studies have furthered our mechanistic understanding of these interactions in pathophysiological settings and delineated potential clinical outcomes. In addition, emerging evidence suggests that the canonical nitroxidative species (NO, superoxide, and/or peroxynitrite) modulate biosynthesis of prostaglandins through non-COX-related pathways. This article provides a comprehensive state-of-the art overview in this area.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Shujing Jin ◽  
Xun Qi ◽  
Bin Zhang ◽  
Ziqing Sun ◽  
Bingchun Zhang ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sija Landman ◽  
Chiel van der Horst ◽  
Piet E. J. van Erp ◽  
Irma Joosten ◽  
Rob de Vries ◽  
...  

AbstractInflammatory disorders like diabetes, systemic lupus erythematodes, inflammatory lung diseases, rheumatoid arthritis and multiple sclerosis, but also rejection of transplanted organs and GvHD, form a major burden of disease. Current classes of immune suppressive drugs to treat these disorders are never curative and side effects are common. Therefore there is a need for new drugs with improved and more targeted modes of action. Potential candidates are the DNA methyl transferase inhibitor 5-azacytidine (Aza) and its derivative 5-aza 2′deoxycitidine (DAC). Aza and DAC have been tested in several pre-clinical in vivo studies. In order to obtain an overview of disorders for which Aza and/or DAC can be a potential treatment, and to find out where information is lacking, we systematically reviewed pre-clinical animal studies assessing Aza or DAC as a potential therapy for distinct inflammatory disorders. Also, study quality and risk of bias was systematically assessed. In the 35 identified studies, we show that both Aza and DAC do not only seem to be able to alleviate a number of inflammatory disorders, but also prevent solid organ rejection and GvHD in in vivo pre-clinical animal models. Aza/DAC are known to upregulate FOXP3, a master transcription factor for Treg, in vitro. Seventeen studies described the effect on Treg, of which 16 studies showed an increase in Treg. Increasing Treg therefore seems to be a common mechanism in preventing inflammatory disorders by Aza/DAC. We also found, however, that many essential methodological details were poorly reported leading to an unclear risk of bias. Therefore, reported effects might be an overestimation of the true effect.


Author(s):  
Mr. Chate Mahesh Madhukar

Abstract: Pomegranates fruits have innumerable health benefits and its implication in diseases cure have been widely recognized since ancient time. Moreover, pomegranate fruits, seeds and peels are intensively used in traditional medicine as a natural therapy. It contains numerous valuable ingredients such as flavonoids, ellagitannin, punicalagin, ellagic acid, vitamins and minerals. The principal constituents including punicalagins and ellagitannin are responsible for immeasurable health benefits due to its strong antioxidant activity. Additionally, constituents of pomegranate show health promoting effect through the modulation of physiological and biochemical pathways. Recent evidences suggested that pomegranates fruits, peels and seeds illustrate therapeutics implications in health management via inhibition of free radical effect and modulation of enzymes activity linked with diseases development and progression. In this review, we summarize the therapeutic role of pomegranate fruits, seeds and peels in the health managements based on in vitro and in vivo studies. Keywords: Pomegranates, Anti-oxidant, Anti-inflammatory effect, Heptoprotective effect, Neuroprotective effect and antimicrobial effects.


Author(s):  
Mahboubeh Bozorgi ◽  
◽  
Zahra Najafi ◽  
Sahar Omidpanah ◽  
Arash Sadri ◽  
...  

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. Sever cognitive and memory impairments, huge increase in the prevalence of the disease, and lacking definite cure have absorbed worldwide efforts to develop therapeutic approaches. Since many drugs have failed in the clinical trials due to multifactorial nature of AD, symptomatic treatments are still in the center attention and now, nootropic medicinal plants have been found as versatile ameliorators to reverse memory disorders. In this work, anti-Alzheimer’s activity of aqueous extract of areca nuts (Areca catechu L.) was investigated via in vitro and in vivo studies. It depicted good amyloid β (Aβ) aggregation inhibitory activity, 82% at 100 µg/mL. In addition, it inhibited beta-secretase 1 (BACE1) with IC50 value of 19.03 µg/mL. Evaluation of neuroprotectivity of the aqueous extract of the plant against H2O2-induced cell death in PC12 neurons revealed 84.5% protection at 1 µg/mL. It should be noted that according to our results obtained from Morris Water Maze (MWM) test, the extract reversed scopolamine-induced memory deficit in rats at concentrations of 1.5 and 3 mg/kg.


Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1253
Author(s):  
Ajay Ashok ◽  
Suman Chaudhary ◽  
Aaron S. Wise ◽  
Neil A. Rana ◽  
Dallas McDonald ◽  
...  

To evaluate the role of iron in sodium iodate (NaIO3)-induced model of age-related macular degeneration (AMD) in ARPE-19 cells in-vitro and in mouse models in-vivo. ARPE-19 cells, a human retinal pigment epithelial cell line, was exposed to 10 mM NaIO3 for 24 h, and the expression and localization of major iron modulating proteins was evaluated by Western blotting (WB) and immunostaining. Synthesis and maturation of cathepsin-D (cat-D), a lysosomal enzyme, was evaluated by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) and WB, respectively. For in-vivo studies, C57BL/6 mice were injected with 40 mg/kg mouse body weight of NaIO3 intraperitoneally, and their retina was evaluated after 3 weeks as above. NaIO3 induced a 10-fold increase in ferritin in ARPE-19 cells, which co-localized with LC3II, an autophagosomal marker, and LAMP-1, a lysosomal marker. A similar increase in ferritin was noted in retinal lysates and retinal sections of NaIO3-injected mice by WB and immunostaining. Impaired synthesis and maturation of cat-D was also noted. Accumulated ferritin was loaded with iron, and released from retinal pigmented epithelial (RPE) cells in Perls’ and LAMP-1 positive vesicles. NaIO3 impairs lysosomal degradation of ferritin by decreasing the transcription and maturation of cat-D in RPE cells. Iron-loaded ferritin accumulates in lysosomes and is released in lysosomal membrane-enclosed vesicles to the extracellular milieu. Accumulation of ferritin in RPE cells and fusion of ferritin-containing vesicles with adjacent photoreceptor cells is likely to create an iron overload, compromising their viability. Moreover, reduced activity of cat-D is likely to promote accumulation of other cellular debris in lysosomal vesicles, contributing to AMD-like pathology.


Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1257
Author(s):  
Gloria Magro ◽  
Arianna Calistri ◽  
Cristina Parolin

The presence of latently infected cells and reservoirs in HIV-1 infected patients constitutes a significant obstacle to achieve a definitive cure. Despite the efforts dedicated to solve these issues, the mechanisms underlying viral latency are still under study. Thus, on the one hand, new strategies are needed to elucidate which factors are involved in latency establishment and maintenance. On the other hand, innovative therapeutic approaches aimed at eradicating HIV infection are explored. In this context, advances of the versatile CRISPR-Cas gene editing technology are extremely promising, by providing, among other advantages, the possibility to target the HIV-1 genome once integrated into cellular DNA (provirus) and/or host-specific genes involved in virus infection/latency. This system, up to now, has been employed with success in numerous in vitro and in vivo studies, highlighting its increasing significance in the field. In this review, we focus on the progresses made in the use of different CRISPR-Cas strategies to target the HIV-1 provirus, and we then discuss recent advancements in the use of CRISPR screens to elucidate the role of host-specific factors in viral latency.


Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 102
Author(s):  
Phuong H.L. Tran ◽  
Thao T.D. Tran

Blueberries are consumed as healthy fruits that provide a variety of benefits to the nervous system. Scientists have found that blueberries can be used as a daily edible source for supplementation to prevent and minimize complexities of age-related diseases as well as to improve learning and memory in children. Anthocyanins are the most mentioned compounds among the components in blueberries, as they play a major role in providing the health benefits of this fruit. However, while they are highly active in impeding biological impairment in neuronal functions, they have poor bioavailability. This review focuses on neurological investigations of blueberries from in vitro cell studies to in vivo studies, including animal and human studies, with respect to their positive outcomes of neuroprotection and intervention in neurodegenerative conditions. Readers will also find information on the bioavailability of anthocyanins and the considerable factors affecting them so that they can make informed decisions regarding the daily consumption of blueberries. In this context, the ways in which blueberries or blueberry supplementation forms are consumed and which of these forms is best for maximizing the health benefits of blueberries should be considered important decision-making factors in the consumption of blueberries; all of these aspects are covered in this review. Finally, we discuss recent technologies that have been employed to improve the bioavailability of blueberry anthocyanins in the development of effective delivery vehicles supporting brain health.


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