Quercetin is a ubiquitous flavonoid that is present in numerous plants that are utilized in many different cultures for their nervous system and anticancer effects. To better understand the neuroprotective and antiproliferative activities of quercetin, we present a comprehensive review of the divergent actions that contribute to the ethnopharmacological profile of these plants.
The pharmacological activities of quercetin that modulate antioxidation/oxidation/kinase-signaling pathways might be differentially elicited in neurons compared with malignant cells, ultimately promoting cell survival or death in a cell type- and metabolism-specific manner. Whereas the broad antioxidation and anti-inflammatory activities of quercetin are important for neuronal survival, the oxidative, kinase- and cell cycle-inhibitory, apoptosis-inducing effects of quercetin are essential for its anticancer effects. The diverse mechanistic interactions and activities of quercetin that modulate the phosphorylation state of molecules as well as gene expression would alter the interconnected and concerted intracellular signaling equilibrium, either inhibiting or strengthening survival signals. These mechanisms, which have been mainly observed in in vitro studies, cannot be easily translated into an explanation of the divergent simultaneous neuroprotective and anticancer effects observed in vivo. This is in part due to low bioavailability in plasma and in the brain, as well as the nature of the actual active molecules.
Numerous studies have demonstrated the beneficial effects of chronic quercetin intake, which is ethnopharmacologically meaningful, as many plants that are chronically ingested by people contain quercetin. Although quercetin and quercetin-containing plants exhibit potential as therapeutic modalities in neuropathology and in cancer, the data collectively highlight the need to elucidate issues such as bioavailability as well as its correlation with effectiveness at biomarkers in vivo. There would be an increased potentential of these plants for chemoprevention and neuropathology prevention.
"Quercetin has emerged as a potential therapeutic agent for treatment of various types of cancers owing to its ability to induce apoptosis. Several articles have suggested mechanisms implicated in the proapoptotic properties of this compound involving activation of kinases, downregulation of survival pathways, ROS production, mitochondrial potential perturbation, release of cytochrome c, and, in consequence, activation of caspase-3 and caspase-9      . A body of literature also describes [ "
[Show abstract][Hide abstract] ABSTRACT: Background:
High expression of HSP27 and HSP72 in glioma cells has been closely associated with chemoresistance and decreased sensitivity to programmed cell death induction. Therefore, it is important to devise therapies that effectively target invasive cancer cells by inducing cell death. The aim of our study was to assess the effect of quercetin and imperatorin applied separately and in combinations on the apoptosis and autophagy induction in human T98G cells cultured in vitro.
Cell death induction was analyzed by the staining method. The Western blotting technique and fluorimetric measurements of activity were used to assess the expression of marker proteins of apoptosis and autophagy. The specific siRNA transfected method was used for blocking of the expression of HSP27 and HSP72 genes.
The experiments revealed the highest percentage of apoptotic cells after using a 50?M concentration of both compounds. Simultaneous quercetin and imperatorin administration induced apoptosis more effectively than incubation with single drugs. These results were accompanied with decreased HSP27 and HSP72 expression, and a high level of caspase-3 and caspase-9 activity. Autophagy was not observed. Additional experiments were performed on a cell line with blocked Hsp27 and Hsp72 expression and significant increase the sensitivity to apoptosis induction upon quercetin and imperatorin treatment was noticed.
The present study indicates that quercetin and imperatorin are potent apoptosis inducers, especially when they act synergistically, which may be a promising combination useful in glioma therapy. Our results also demonstrated that blocking the HSP27 and HSP72 gene expression might serve as a therapeutic target for the human brain cancer.
"Flavonoids are natural polyphenols with well-known antioxidant and scavenger characteristics . Furthermore, flavonoids show cytoprotective effects and are considered to be promising agents in prevention and/or therapy of numerous disorders    . "
[Show abstract][Hide abstract] ABSTRACT: Diosmetin (DIOS) is a flavone aglycone commonly occurring in citrus species and olive leaves, in addition it is one of the active ingredients of some medications. Based on both in vitro and in vivo studies several beneficial effects are attributed to DIOS but the biochemical background of its action seems to be complex and it has not been completely explored yet. Previous investigations suggest that most of the flavonoid aglycones have negative effect on ATP synthesis in a dose dependent manner. In our study 17 flavonoids were tested and interestingly DIOS caused a significant elevation of intracellular ATP levels after 6- and 12-h incubation in MDCK kidney cells. In order to understand the mechanism of action, intracellular ATP and protein levels, ATP/ADP ratio, cell viability and ROS levels were determined after DIOS treatment. In addition, impacts of different enzyme inhibitors and effect of DIOS on isolated rat liver mitochondria were also tested. Finally, the influence of DIOS on the ATP depleting effect of the mycotoxin, ochratoxin A was also investigated. Our major conclusions are the followings: DIOS increases intracellular ATP levels both in kidney and in liver cells. Inhibition of glycolysis or citric acid cycle does not decrease the observed effect. DIOS-induced elevation of ATP levels is completely abolished by the inhibition of ATP synthase. DIOS is able to completely reverse the ATP-depleting effect of the mycotoxin, ochratoxin A. Most probably the DIOS-induced impact on ATP system does not originate from the antioxidant property of DIOS. Based on our findings DIOS may be promising agent to positively influence ATP depletion caused by some metabolic poisons.
Journal of photochemistry and photobiology. B, Biology 01/2014; 132C:1-9. DOI:10.1016/j.jphotobiol.2014.01.016 · 2.96 Impact Factor
"Several previous studies suggested that flavonoids may act as antioxidants, free-radical scavengers and radioprotectors 41. Quercetin is a ubiquitous flavonoid that is present in numerous plants that are utilised in many different cultures for their nervous system and anticancer effects 42,43. Quercetin plays an important role in altering the progression of neurodegenerative diseases by its protective effect against oxidative stress 44. "
[Show abstract][Hide abstract] ABSTRACT: Quercetin has been demonstrated to play an important role in altering the progression of ischemic brain injuries and neurodegenerative diseases by protecting against oxidative stress. The effects of quercetin on brain damage after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of quercetin on oxidative stress and brain edema after experimental SAH using four equal groups (n = 16) of adult male Sprague-Dawley (SD) rats, including a sham group, an SAH + vehicle group, an SAH + quercetin10 group, and an SAH + quercetin50 group. The rat SAH model was induced by injection of 0.3 ml of non-heparinised arterial blood into the prechiasmatic cistern. In the SAH + quercetin10 and SAH + quercetin50 groups, doses of 10 mg/kg and 50 mg/kg quercetin, respectively, were directly administered by intraperitoneal injection at 30 min, 12 h, and 24 h after SAH induction. Cerebral tissue samples were extracted for enzymatic antioxidant determination, lipid peroxidation assay, caspase-3 activity and water content testing 48 h after SAH. Treatment with a high dose (50 mg/kg) of quercetin markedly enhanced the activities of copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), and treatment with this dose significantly reduced the level of malondialdehyde (MDA). Caspase-3 and brain edema was ameliorated and neurobehavioral deficits improved in rats that received the high dose of quercetin. The findings suggest that the early administration of optimal dose of quercetin may ameliorate brain damage and provide neuroprotection in the SAH model, potentially by enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation.
International journal of medical sciences 01/2014; 11(3):282-90. DOI:10.7150/ijms.7634 · 2.00 Impact Factor
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