scholarly journals Flavonoids and Mitochondria: Activation of Cytoprotective Pathways?

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3060 ◽  
Author(s):  
Anna Kicinska ◽  
Wieslawa Jarmuszkiewicz

A large number of diverse mechanisms that lead to cytoprotection have been described to date. Perhaps, not surprisingly, the role of mitochondria in these phenomena is notable. In addition to being metabolic centers, due to their role in cell catabolism, ATP synthesis, and biosynthesis these organelles are triggers and/or end-effectors of a large number of signaling pathways. Their role in the regulation of the intrinsic apoptotic pathway, calcium homeostasis, and reactive oxygen species signaling is well documented. In this review, we aim to characterize the prospects of influencing cytoprotective mitochondrial signaling routes by natural substances of plant origin, namely, flavonoids (e.g., flavanones, flavones, flavonols, flavan-3-ols, anthocyanidins, and isoflavones). Flavonoids are a family of widely distributed plant secondary metabolites known for their beneficial effects on human health and are widely applied in traditional medicine. Their pharmacological characteristics include antioxidative, anticarcinogenic, anti-inflammatory, antibacterial, and antidiabetic properties. Here, we focus on presenting mitochondria-mediated cytoprotection against various insults. Thus, the role of flavonoids as antioxidants and modulators of antioxidant cellular response, apoptosis, mitochondrial biogenesis, autophagy, and fission and fusion is reported. Finally, an emerging field of flavonoid-mediated changes in the activity of mitochondrial ion channels and their role in cytoprotection is outlined.

2006 ◽  
Vol 80 (1) ◽  
pp. 395-403 ◽  
Author(s):  
Yin Liu ◽  
Yinghui Pu ◽  
Xuming Zhang

ABSTRACT A previous study demonstrated that infection of rat oligodendrocytes by mouse hepatitis virus (MHV) resulted in apoptosis, which is caspase dependent (Y. Liu, Y. Cai, and X. Zhang, J. Virol. 77:11952-11963, 2003). Here we determined the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis. We found that caspase-9 activity was 12-fold higher in virus-infected cells than in mock-infected cells at 24 h postinfection (p.i.). Pretreatment of cells with a caspase-9 inhibitor completely blocked caspase-9 activation and partially inhibited the apoptosis mediated by MHV infection. Analyses of cytochrome c release further revealed an activation of the mitochondrial apoptotic pathway. Stable overexpression of the two antiapoptotic proteins Bcl-2 and Bcl-xL significantly, though only partially, blocked apoptosis, suggesting that activation of the mitochondrial pathway is partially responsible for the apoptosis. To identify upstream signals, we determined caspase-8 activity, cleavage of Bid, and expression of Bax and Bad by Western blotting. We found a drastic increase in caspase-8 activity and cleavage of Bid at 24 h p.i. in virus-infected cells, suggesting that Bid may serve as a messenger to relay the signals from caspase-8 to mitochondria. However, treatment with a caspase-8 inhibitor only slightly blocked cytochrome c release from the mitochondria. Furthermore, we found that Bax but not Bad was significantly increased at 12 h p.i. in cells infected with both live and UV-inactivated viruses and that Bax activation was partially blocked by treatment with the caspase-8 inhibitor. These results thus establish the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis.


Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1709 ◽  
Author(s):  
Maria Teresa Viggiani ◽  
Lorenzo Polimeno ◽  
Alfredo Di Leo ◽  
Michele Barone

Phytoestrogens are natural substances that have been extensively studied for their beneficial effect on human health. Herein, we analyzed the data of the literature on the role of phytoestrogens in the prevention of colorectal neoproliferative lesions (CNL). Both in vitro and in vivo studies suggest that the beneficial effects of phytoestrogens on CNL mainly depend on their ability to bind estrogen receptor beta (ERβ) in the intestinal mucosa and counter ER-alpha (ERα) activity. Epidemiological data demonstrate a correlation between the low prevalence of CNL in Eastern populations and the consumption of soy products (phytoestrogen-enriched diet). However, both observational and interventional studies have produced inconclusive results. In our opinion, these discrepancies depend on an inadequate evaluation of phytoestrogen intake (dietary questionnaires were not aimed at establishing phytoestrogen intake) and absorption (depending mainly on the intestinal microbiota of the analyzed subjects). For this reason, in the present review, we performed an overview of phytoestrogen dietary intake and metabolism to offer the reader the opportunity for a better interpretation of the literature. Future prospective trials focusing on the protective effect of phytoestrogens against CNL should take into account both their dietary intake and absorption, considering the effective role of the intestinal microbiota.


2013 ◽  
Vol 45 (3) ◽  
pp. 106-109 ◽  
Author(s):  
Michael C. Velarde

Estrogen provides many beneficial effects early in life by regulating normal tissue development and several physiological functions. While estrogen replacement therapy (ERT) in women was expected to reduce the health risks associated with the age-related decline in estrogen levels during menopause, ERT also resulted in increased progression to other types of diseases. Hence, distinguishing the signaling pathways that regulate the beneficial and detrimental effects of estrogen is important for developing interventions that selectively harness the hormone's beneficial effects, while minimizing its side effects. Estrogen can minimize mitochondrial dysfunction, which is thought to contribute to aging phenotypes. Decline in estrogen levels during menopause may lead to progressive mitochondrial dysfunction and may permanently alter cellular response, including that of estrogen (i.e., ERT). This review discusses the interplay between estrogen and mitochondrial function during the aging process and suggests a potential role of mitochondria in influencing the pleiotropic action of estrogen.


2019 ◽  
Vol 7 (2A) ◽  
Author(s):  
João Victor Torres de Moraes ◽  
Ricardo Luiz Calazans Luna Filho ◽  
Williams Nascimento de Siqueira ◽  
Hianna Arely Milca Fagundes Silva ◽  
Dewson Rocha Pereira ◽  
...  

Ionizing radiation has been applied in several areas of knowledge, among them the study of the radiomodifier activity of natural substances. These substances can modify the cellular response to the damage induced by the radiation. Therefore, this work aimed to evaluate the radiomodifier action of Pityrocarpa moniliformis extract on Biomphalaria glabrata embryos exposed to 60Co gamma radiation. Initially, toxicity tests were performed on the extract against the B. glabrata embryos for the choice of concentration that did not cause death and embryonic malformation. Then, the antioxidant activity of the P. moniliformis extract with flavonoids and phenolic compounds was evaluated by means of the ABTS method. To evaluate the radiomodifier activity of the extract, embryos were selected in the blastula stage and irradiated with 7.5 Gy in a 60Co source (gammacell-Co60). Then, the embryos were exposed for 24 h to the extract of P. moniliformis at a concentration of 250 μg/mL. The results showed that the extract of P. moniliformis presents flavonoids and enzymatic inhibition by ABTS, which demonstrates the presence of antioxidant compounds. However, the tests of the radiomodifier activity did not present radioprotective effect for embryos exposed to ionizing radiation.


2020 ◽  
Vol 16 (5) ◽  
pp. 675-688
Author(s):  
Shamsi Abbasalizadeh ◽  
Behzad Ebrahimi ◽  
Aslan Azizi ◽  
Rogaye Dargahi ◽  
Maryam Tayebali ◽  
...  

Constipation is a common public health concern experienced by all individuals during their life affecting the quality of life. In this paper, we aimed to provide an overview of the existing evidence regarding the role of food ingredients, including bran, prune, fig, kiwifruit, and flax-seed in constipation treatment. We searched Scopus, Pub Med, and Science Direct by using the keywords, “laxative foods” and “constipation”, for searching studies assessing laxative food ingredients and their beneficial effects on constipation treatment and/or control. Lifestyle modifications such as increasing dietary fiber and fluid intake and daily exercise are the proposed first line treatments for constipation. Optimizing ‘diet’ as an efficient lifestyle factor may contribute to the well-being of patients. The use of laxative food ingredients including bran, prune, fig, kiwifruit, flax-seed, probiotics, and prebiotics is a convenient alternative to cope with constipation. According to previous findings, laxative food ingredients could be considered as effective treatments for subjects suffering from constipation. Many studies have assessed the pharmacological and non-pharmacological roles of these ingredients in treating constipation, however, their importance has not been thoroughly investigated.


2020 ◽  
Vol 16 (6) ◽  
pp. 846-853
Author(s):  
Raghunandan Purohith ◽  
Nagendra P.M. Nagalingaswamy ◽  
Nanjunda S. Shivananju

Metabolic syndrome is a collective term that denotes disorder in metabolism, symptoms of which include hyperglycemia, hyperlipidemia, hypertension, and endothelial dysfunction. Diet is a major predisposing factor in the development of metabolic syndrome, and dietary intervention is necessary for both prevention and management. The bioactive constituents of food play a key role in this process. Micronutrients such as vitamins, carotenoids, amino acids, flavonoids, minerals, and aromatic pigment molecules found in fruits, vegetables, spices, and condiments are known to have beneficial effects in preventing and managing metabolic syndrome. There exists a well-established relationship between oxidative stress and major pathological conditions such as inflammation, metabolic syndrome, and cancer. Consequently, dietary antioxidants are implicated in the remediation of these complications. The mechanism of action and targets of dietary antioxidants as well as their effects on related pathways are being extensively studied and elucidated in recent times. This review attempts a comprehensive study of the role of dietary carotenoids in alleviating metabolic syndromewith an emphasis on molecular mechanism-in the light of recent advances.


2019 ◽  
Vol 18 (3) ◽  
pp. 232-238 ◽  
Author(s):  
Emanuela Onesti ◽  
Vittorio Frasca ◽  
Marco Ceccanti ◽  
Giorgio Tartaglia ◽  
Maria Cristina Gori ◽  
...  

Background: The cannabinoid system may be involved in the humoral mechanisms at the neuromuscular junction. Ultramicronized-palmitoylethanolamide (μm-PEA) has recently been shown to reduce the desensitization of Acetylcholine (ACh)-evoked currents in denervated patients modifying the stability of ACh receptor (AChR) function. <p> Objective: To analyze the possible beneficial effects of μm-PEA in patients with myasthenia gravis (MG) on muscular fatigue and neurophysiological changes. <p> Method: The duration of this open pilot study, which included an intra-individual control, was three weeks. Each patient was assigned to a 1-week treatment period with μm-PEA 600 mg twice a day. A neurophysiological examination based on repetitive nerve stimulation (RNS) of the masseteric and the axillary nerves was performed, and the quantitative MG (QMG) score was calculated in 22 MG patients every week in a three-week follow-up period. AChR antibody titer was investigated to analyze a possible immunomodulatory effect of PEA in MG patients. <p> Results: PEA had a significant effect on the QMG score (p=0.03418) and on RNS of the masseteric nerve (p=0.01763), thus indicating that PEA reduces the level of disability and decremental muscle response. Antibody titers did not change significantly after treatment. <p> Conclusion: According to our observations, μm-PEA as an add-on therapy could improve muscular response to fatigue in MG. The possible modulation of AChR currents as a means of eliciting a direct effect from PEA on the conformation of ACh receptors should be investigated. The co-role of cytokines also warrants an analysis. Given the rapidity and reversibility of the response, we suppose that PEA acts directly on AChR, though further studies are needed to confirm this hypothesis.


Author(s):  
Suzanne C. Thompson

A sense of personal control is an important resource that helps people maintain emotional stability and successfully negotiate their way through life. People foster their perceived control by focusing on reachable goals, creating new avenues for control, and accepting difficult-to-change circumstances. In general, perceived control need not be realistic in order to have beneficial effects, although in the area of health promotion, overestimating one's control can reduce the motivation to engage in protection. Research on ethnic differences in the benefits of a sense of personal control suggests that those from more collectivistic cultures or subcultures may be less benefited by a sense of personal control, relying instead on a socially derived sense of control. Successful interventions to enhance personal control include programs that bolster coping skills, give options and decisions to participants, and provide training that encourages attributions to controllable factors. Future research should further explore ethnic differences in the effects of personal control, the consequences of unrealistic control perceptions, and interventions to enhance the sense of control.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1002
Author(s):  
Fabiola Marino ◽  
Mariangela Scalise ◽  
Eleonora Cianflone ◽  
Luca Salerno ◽  
Donato Cappetta ◽  
...  

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.


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