Neuroprotective Effects Of Quercetin Research Articles

Neuroprotective effect of quercetin and nano-quercetin against cyclophosphamide-induced oxidative stress in the rat brain: Role of Nrf2/ HO-1/Keap-1 signaling pathway

Quercetin (Qu) is a powerful flavanol antioxidant that is naturally found in plants and is part of the flavonoid family. Qu has a wide range of biological properties, such as neuroprotective, anti-cancer, anti-diabetic, anti-inflammatory, and radical scavenging capabilities. However, the in vivo application of Qu is limited by its poor water solubility and low bioavailability. These issues could be addressed by utilizing Qu nanoformulations. Cyclophosphamide (CP) is a potent chemotherapeutic agent that causes severe neuronal damage and cognitive impairment due to reactive oxygen species (ROS) overproduction. The present study aimed to explore the proposed neuroprotective mechanism of quercetin (Qu) and quercetin-loaded Chitosan nanoparticles (Qu-Ch NPs) against the brain oxidative damage induced by CP in male albino rats. For this aim, thirty-six adult male rats were randomly divided into six groups (n = 6). Rats were pretreated with Qu and Qu-Ch NPs orally in doses of 10 mg/kg bwt/day for 2 weeks, and CP (75 mg/kg bwt) was administered intraperitoneally 24 h before the termination of the experiment. After 2 weeks, some neurobehavioral parameters were evaluated, and then euthanization was done to collect the brain and blood samples. Results showed that CP induces neurobehavioral deteriorations and impaired brain neurochemical status demonstrated by a significant decrease in brain glutathione (GSH), serum total antioxidant capacity (TAC), and serotonin (5-HT) levels while malondialdehyde (MDA), nitric oxide (NO), Tumor necrosis factor α (TNFα), and choline esterase (ChE) concentrations increased significantly compared to the control group. Pretreatment with Qu and Qu-Ch NPs showed a significant anti-oxidative, anti-depressive, and neuroprotective effect through modification of the above-mentioned parameters. The results were further validated by assessing the expression levels of selected genes in brain homogenates and histopathological investigations were done to pinpoint the exact brain-altered regions. It could be concluded that Qu and Qu-Ch NPs can be useful neuroprotective adjunct therapy to overcome neurochemical damage induced by CP.

Neuroprotective effect of quercetin and Zingiber officinale on sodium arsenate-induced neurotoxicity in rats.

The study was aimed at determining the ameliorative potential of quercetin and Zingiber officinale (ZO) against sodium arsenate-induced neurotoxicity in male Wistar rats. Thirty adult animals were randomly allocated to five groups (n=6). Group I served as control, groups II and IV were treated with ZO [300 mg/kg, PO (per os)/day], and group V animals were administered quercetin (50 mg/kg, PO/day) for 18 days. Groups III, IV, and V were injected with sodium arsenate (20 mg/kg, intraperitoneally/day) for 4 days starting from day 15. The administration of sodium arsenate resulted in a significant decrease in total antioxidant status, total thiols, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and aryl esterase in brain tissue of the animals compared with the control group. In addition, a significant increase was observed in malondialdehyde, advanced oxidation protein product and plasma nitric oxide levels, indicating oxidative stress-mediated neuronal damage. However, these arsenic-induced alterations were significantly reversed by quercetin or ZO in the treatment groups, indicating their ameliorative potential. These positive effects were further confirmed by histopathological examination of brain tissue revealing the suppression of severe neuronal injury, spongiosis and gliosis in the samples pretreated with quercetin and ZO. Our results suggest that inclusion of ZO and quercetin-rich foods in the diet can help in preventing the neurotoxic effects in areas with elevated levels of arsenic in food chain and ground water.

Neuroprotective Effect of Quercetin and Memantine against AlCl3-Induced Neurotoxicity in Albino Wistar Rats.

Recent evidences indicate that there is a substantial increase in worldwide cases of dementia. Alzheimer's disease is the leading cause of dementia and may contribute to 60-70% of cases. Quercetin is a unique bioflavonoid that has numerous therapeutic benefits such as anti-allergy, anti-ulcer, anti-inflammatory, anti-hypertensive, anti-cancer, immuno-modulatory, anti-infective, antioxidant, acetylcholinesterase inhibitory activity, neuroprotective effects, etc. In the present study, we evaluated the neuroprotective effect of orally administered quercetin with memantine in albino Wistar rats after inducing neurotoxicity through AlCl3 (100 mg/kg, p.o.). Chronic administration of AlCl3 resulted in poor retention of memory and significant oxidative damage. Various behavioral parameters, such as locomotor activity, Morris water maze, elevated plus maze, and passive avoidance test, were assessed on days 21 and 42 of the study. The animals were euthanatized following the completion of the last behavioral assessment. Various oxidative stress parameters were assessed to know the extent of oxidative damage to brain tissue. Quercetin with memantine has shown significant improvement in behavioral studies, inhibition of AChE activity, and reduction in oxidative stress parameters. Histopathological studies assessed for cortex and hippocampus using hematoxylin and eosin (H&E), and Congo red stain demonstrated a reduction in amyloid-β plaque formation after treatment of quercetin with memantine. Immunohistochemistry showed that quercetin with memantine treatment also improved the expression of brain-derived neurotrophic factor (BDNF) and inhibited amyloid-β plaque formation. The present study results demonstrated protective effects of treatment of quercetin with memantine in the neurotoxicity linked to aluminum chloride in albino Wistar rats.

ASCERTAINING THE ANTIOXIDANT PROPERTIES OF QUERCETIN AGAINST OXIDATIVE STRESS IN COMBATING ALZHEIMER’S DISEASE: A REVIEW

Quercetin is a flavonoid compound mostly found in plants including fruits, vegetables, green tea, red wine etc. Apart from having many health effects, quercetin possesses antioxidant capacities. It can scavenge hydroxyl radical (OH-), hydrogen peroxide (H2O2), nitric oxide (NO) and other free radicals. The reactive oxygen species have high potential to interrupt the functions of lipids, proteins, DNA and RNA which can lead to various epigenetic changes. These components in the neurons are more vulnerable to oxidative stress. Mitochondrial dysfunctions, amyloidopathy, taopathy, metal accumulation, synaptic dysfunctions, genetic and neuro- inflammation can cause oxidative stress in a cell, which is responsible for development of Alzheimer’s disease (AD). The relationship between oxidative stress and AD suggests that oxidative stress is an important contributor of the pathological process for AD and antioxidants may be useful for the treatment. It is proposed that quercetin would be the best choice to act against oxidative stress and hence to AD as it has antioxidant properties as well can inhibit the crowding of macromolecules such as Aβ, Tau protein etc. The neuroprotective effects of quercetin are regulated through nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Paraoxonase-2, c-Jun- N-terminal kinase (JNK), Protein kinase C, Mitogen-activated protein kinase (MAPK) and PI3K/AKt pathways. Therefore the aim of this review is to study the antioxidant effects of quercetin against oxidative stress and hence to prevent the pathogenesis of AD.

Involvement of Microbiome Gut-Brain Axis in Neuroprotective Effect of Quercetin in Mouse Model of Repeated Mild Traumatic Brain Injury.

Repeated mild traumatic brain injury (rmTBI) poses adversity in the form of neurological deficits. The ignition of long-term neurological aberrations post-TBI is appended with the microbiota gut-brain axis perturbation. Herein, we examined whether quercetin, which is anti-inflammatory and antioxidant flavonoid, serves as a prebiotic and modifies the compromised microbiome gut-brain axis in rmTBI mouse model. Male C57BL/6 mice were subjected to rmTBI for 7 times. The quercetin (50mg/kg) was administered peroral from the day1 of first injury till 7days post-injury. The neurobehavioral assessments were performed using return of righting reflex (ROR), rotarod, forced swimming test (FST), elevated zero maze (EZM), novel object recognition test (NORT), and Y-maze. Mice fecal samples, brains, and intestines were collected for molecular studies. Mice underwent rmTBI showed significant neurological deficits in ROR and rotarod test and also exhibited long-term neuropsychiatric aberrations like anxiety- and depression-like phenotypes, and cognitive deficits in EZM, FST, and Y-maze assays, respectively. Repeated peroral administration of quercetin ameliorated these neuropsychiatric problems. Quercetin treatment also restored the increased expression of GFAP and decreased expression of occludin and doublecortin in the frontal cortex and hippocampus of rmTBI mice. The altered levels of acetate and propionate, and microbial phylum abundance in fecal samples were also normalized in the quercetin-treated group. We also noted an improved intestinal permeability indicated by reduced villi rupture, blunting, and mucosal thinning in quercetin-treated mice. We suggest that the neuroprotective effect of quercetin may be mediated via remodeling of the microbiome gut-brain axis in rmTBI mouse model.

A Critical Analysis of Quercetin as the Attractive Target for the Treatment of Parkinson's Disease.

Parkinson's Disease (PD) is a multifaceted disorder with various factors suggested to play a synergistic pathophysiological role, such as oxidative stress, autophagy, pro-inflammatory events, and neurotransmitter abnormalities. While it is crucial to discover new treatments in addition to preventing PD, recent studies have focused on determining whether nutraceuticals will exert neuroprotective actions and pharmacological functions in PD. Quercetin, a flavonol-type flavonoid, is found in many fruits and vegetables and is recognised as a complementary therapy for PD. The neuroprotective effect of quercetin is directly associated with its antioxidant activity, in addition to stimulating cellular defence against oxidative stress. Other related mechanisms are activating Sirtuins (SIRT1) and inducing autophagy, in addition to induction of Nrf2-ARE and Paraoxonase 2 (PON2). Quercetin, whose neuroprotective activity has been demonstrated in many studies, unfortunately, has a disadvantage because of its poor water solubility, chemical instability, and low oral bioavailability. It has been reported that the disadvantages of quercetin have been eliminated with nanocarriers loaded with quercetin. The role of nanotechnology and nanodelivery systems in reducing oxidative stress during PD provides an indisputable advantage. Accordingly, the present review aims to shed light on quercetin's beneficial effects and underlying mechanisms in neuroprotection. In addition, the contribution of nanodelivery systems to the neuroprotective effect of quercetin is also discussed.

Quercetin and lycopene co-administration prevents oxidative damage induced by d-galactose in mice

Quercetin and lycopene are strong dietary antioxidants that often co-exist in foods. Here, the cardiac and neuroprotective effects of quercetin and lycopene combination were analyzed in d-galactose-induced oxidative stress in mice. ICR mice were divided into control group, d-galactose group (D-GAL), quercetin treatment (Q45: 45 mg kg−1 d−1quercetin, Q60: 60 mg kg−1 d−1 quercetin), lycopene treatment (15 mg kg−1 d−1 lycopene), and M groups (45 mg kg−1 d−1quercetin+15 mg kg−1 d−1 lycopene). Mice were given quercetin, lycopene, and their combination through oral gavage for 6 weeks. They were injected with d-galactose (150 mg kg−1 d−1) simultaneously except for the control group. Results showed that the quercetin-lycopene combination could ameliorate histopathological injuries in the heart and hippocampus. They significantly decreased the serum and heart malonaldehyde (MDA) levels, heart 4-Hydroxynonenal (4-HNE) levels, and increased the activity of serum and heart superoxide dismutase (SOD), catalase (CAT), and the hippocampal SOD and CAT mRNA level. Quercetin-lycopene combination exhibited anti-inflammation effects by reducing inflammatory genes such as cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β). The heart and hippocampal mRNA level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression was up-regulated, and the antioxidant genes related to Nrf2 including heme oxygenase-1 (HO-1), NAD(P)H Quinone Dehydrogenase 1 (NQO1) were elevated. Quercetin-lycopene combination significantly promoted the mRNA level of deacetylase sirtuin-1 (SIRT1), increased 3.3-fold and 3-fold SIRT1 expression in the heart and hippocampus, respectively. They could bind SIRT1 at the active site predicted by molecular docking. These results suggested that they may interact with SIRT1 to activate Nrf2, inhibit pro-inflammatory factors, and prevent oxidative stress in D-GAL-induced mice.

Neuroprotective effects of quercetin on the cerebellum of zinc oxide nanoparticles (ZnoNps)-exposed rats

ABSTRACT Engineered nanomaterials induce hazardous effects at the cellular and molecular levels. We investigated different mechanisms underlying the neurotoxic potential of zinc oxide nanoparticles (ZnONPs) on cerebellar tissue and clarified the ameliorative role of Quercetin supplementation. Forty adult male albino rats were divided into control group (I), ZnONPs-exposed group (II), and ZnONPs and Quercetin group (III). Oxidative stress biomarkers (MDA & TOS), antioxidant biomarkers (SOD, GSH, GR, and TAC), serum interleukins (IL-1β, IL-6, IL-8), and tumor necrosis factor alpha (TNF-α) were measured. Serum micro-RNA (miRNA): miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-3p expression levels were quantified by real-time quantitative polymerase-chain reaction (RT-QPCR). Cerebellar tissue sections were stained with Hematoxylin & Eosin and Silver stains and examined microscopically. Expression levels of Calbindin D28k, GFAP, and BAX proteins in cerebellar tissue were detected by immunohistochemistry. Quercetin supplementation lowered oxidative stress biomarkers levels and ameliorated the antioxidant parameters that were decreased by ZnONPs. No significant differences in GR activity were detected between the study groups. ZnONPs significantly increased serum IL-1β, IL-6, IL-8, and TNF-α which were improved with Quercetin. Serum miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-p expression levels showed significant increase in ZnONPs group, while no significant difference was observed between Quercetin-treated group and control group. ZnONPs markedly impaired cerebellar tissue structure with decreased levels of calbindin D28k, increased BAX and GFAP expression. Quercetin supplementation ameliorated cerebellar tissue apoptosis, gliosis and improved calbindin levels. In conclusion: Quercetin supplementation ameliorated cerebellar neurotoxicity induced by ZnONPs at cellular and molecular basis by different studied mechanisms.Abbreviations: NPs: Nanoparticles, ROS: reactive oxygen species, ZnONPs: Zinc oxide nanoparticles, AgNPs: silver nanoparticles, BBB: blood–brain barrier, ncRNAs: Non-coding RNAs, miRNA: Micro RNA, DMSO: Dimethyl sulfoxide, LPO: lipid peroxidation, MDA: malondialdehyde, TBA: thiobarbituric acid, TOS: total oxidative status, ELISA: enzyme-linked immunosorbent assay, H2O2: hydrogen peroxide, SOD: superoxide dismutase, GR: glutathione reductase, TAC: total antioxidant capacity, IL-1: interleukin-1, TNF: tumor necrosis factor alpha, cDNA: complementary DNA, RT-QPCR: Real-time quantitative polymerase-chain reaction, ABC: Avidin biotin complex technique, DAB: 3′, 3-diaminobenzidine, SPSS: Statistical Package for Social Sciences, ANOVA: One way analysis of variance, Tukey’s HSD: Tukey’s Honestly Significant Difference, GFAP: glial fiberillar acitic protein, iNOS: Inducible nitric oxide synthase, NO: nitric oxide, HO-1: heme oxygenase-1, Nrf2: nuclear factor erythroid 2-related factor 2, NF-B: nuclear factor-B, SCI: spinal cord injury, CB: Calbindin

Neuroprotective effect of quercetin against rotenone-induced neuroinflammation and alterations in mice behavior.

Various studies suggested that neuroinflammation leads to the development of several neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), andHuntington's disease (HD). Rotenone is an organic pesticide and potent inhibitor of complex I of electron transport chain widely used to develop the PD model. Numerous studies reported rotenone toxicity in the dopaminergic system but very few studies are available on rotenone-induced glial cell activation and subsequent neurodegeneration and alterations in various types of behavior. Therefore, the present study was designed to explore the effect of rotenone on neuroinflammation and its deleterious effect on the behavior of mice, and also how these effects can be protected through quercetin. Quercetin, a natural flavonoid having strong antioxidant and anti-inflammatory properties, is found in vegetables and fruits. The finding of the study indicated that rotenone 5 mg/kg body weight for 60 days through oral gavage leads to the release of inflammatory markers in blood serum, astrocytes activation in substantia nigra and hippocampus, and subsequently decreased density of dopaminergic fibers in the striatum. Rotenone also altered the memory of the mice as indicated by decreased spontaneous alteration in Y-maze and T-maze tests and reduction in exploration time in novel object recognition, increased immobility time in theforced swim testand reduced muscular strength. Co-treatment of quercetin 30 mg/kg/day through oral gavage for 60 days along with rotenone significantly reversed all these adverse effects, suggesting that quercetin could reduce neuroinflammation, and improve memory, and cognitive function.

Neuroprotective Effects of Quercetin on Ischemic Stroke: A Literature Review.

Ischemic stroke (IS) is characterized by high recurrence and disability; however, its therapies are very limited. As one of the effective methods of treating acute attacks of IS, intravenous thrombolysis has a clear time window. Quercetin, a flavonoid widely found in vegetables and fruits, inhibits immune cells from secreting inflammatory cytokines, thereby reducing platelet aggregation and limiting inflammatory thrombosis. In pre-clinical studies, it has been shown to exhibit neuroprotective effects in patients with ischemic brain injury. However, its specific mechanism of action remains unknown. Therefore, this review aims to use published data to elucidate the potential value of quercetin in patients with ischemic brain injury. This article also reviews the plant sources, pharmacological effects, and metabolic processes of quercetin in vivo, thus focusing on its mechanism in inhibiting immune cell activation and inflammatory thrombosis as well as promoting neuroprotection against ischemic brain injury.

Quercetin Modulates Behavioural and Biochemical Alterations in Stressed Mice

Disruption of the active phase of sleep alters the physiological homeostasis of the body and results in oxidative breakdown which may trigger a wide array of defects. The central nervous system and the metabolic system are some of the most affected systems as described in several literatures. Some plant based compounds with antioxidant property have been previously described in the abrogation of the deleterious effects of active sleep disruption. One of such compounds is quercetin. This study was premeditated to expatiate on the probable neuroprotective effect of quercetin on mice exposed to 72hr active sleep disruption. Mice were allotted into five treatment groups (n = 6): group 1 served as control, group 2 received 10 mL/kg vehicle, groups 3 and 4 received 25 and 50 mg/kg quercetin respectively, and group 5 received 50 mg/kg astaxanthin. Treatment lasted for 7 days while groups 2-5 were exposed to the sleep deprivation protocol starting from day 4. Behavioural tests followed by biochemical assays and histopathological changes in the prefrontal cortex were evaluated. Data were analysed by ANOVA set at p<0.05 significance. The results revealed that quercetin, in both doses, significantly amplified memory performance, attenuated depression-like behaviour, replenished catalase and superoxide dismutase, attenuated nitric oxide levels in brain and liver of mice when compared to control group and protected against loss of prefrontal cortex neurons. In conclusion, quercetin possesses protective effects against sleep deprivation-induced brain damage.

Cholinesterase Inhibitory Potential of Quercetin towards Alzheimer's Disease - A Promising Natural Molecule or Fashion of the Day? - A Narrowed Review.

Natural substances are known to have strong protective effects against neurodegenerative diseases. Among them, phenolic compounds, especially flavonoids, come to the fore with their neuroprotective effects. Since quercetin, which is found in many medicinal plants and foods, is also taken through diet, its physiological effects on humans are imperative. Many studies have been published up to date on the neuroprotective properties of quercetin, a flavanol derivative. However, there is no review published so far summarizing the effect of quercetin on the cholinesterase (ChE) enzymes related to the cholinergic hypothesis, which is one of the pathological mechanisms of Alzheimer's Disease (AD). However, ChE inhibitors, regardless of natural or synthetic, play a vital role in the treatment of AD. Although the number of studies on the ChE inhibitory effect of quercetin is limited, it deserves to be discussed in a review article. With this sensitivity, the neuroprotective effect of quercetin against AD through ChE inhibition was scrutinized in the current review study. In addition, studies on the bioavailability of quercetin and its capacity to cross the blood-brain barrier and how this capacity and bioavailability can be increased were given. Generally, studies containing data published in recent years were obtained from search engines such as PubMed, Scopus, and Medline and included herein. Consequently, quercetin should not be considered as a fashionable natural compound and should be identified as a promising compound, especially with increased bioavailability, for the treatment of AD.

Neuroprotective Effect of Quercetin during Cerebral Ischemic Injury Involves Regulation of Essential Elements, Transition Metals, Cu/Zn Ratio, and Antioxidant Activity.

Cerebral ischemia results in increased oxidative stress in the affected brain. Accumulating evidence suggests that quercetin possesses anti-oxidant and anti-inflammatory properties. The essential elements magnesium (Mg), zinc (Zn), selenium (Se), and transition metal iron (Fe), copper (Cu), and antioxidants superoxide dismutase (SOD) and catalase (CAT) are required for brain functions. This study investigates whether the neuroprotective effects of quercetin on the ipsilateral brain cortex involve altered levels of essential trace metals, the Cu/Zn ratio, and antioxidant activity. Rats were intraperitoneally administered quercetin (20 mg/kg) once daily for 10 days before ischemic surgery. Cerebral ischemia was induced by ligation of the right middle cerebral artery and the right common carotid artery for 1 h. The ipsilateral brain cortex was homogenized and the supernatant was collected for biochemical analysis. Results show that rats pretreated with quercetin before ischemia significantly increased Mg, Zn, Se, SOD, and CAT levels, while the malondialdehyde, Fe, Cu, and the Cu/Zn ratio clearly decreased as compared to the untreated ligation subject. Taken together, our findings suggest that the mechanisms underlying the neuroprotective effects of quercetin during cerebral ischemic injury involve the modulation of essential elements, transition metals, Cu/Zn ratio, and antioxidant activity.

Neuropharmacological Effects of Quercetin: A Literature-Based Review

Quercetin (QUR) is a natural bioactive flavonoid that has been lately very studied for its beneficial properties in many pathologies. Its neuroprotective effects have been demonstrated in many in vitro studies, as well as in vivo animal experiments and human trials. QUR protects the organism against neurotoxic chemicals and also can prevent the evolution and development of neuronal injury and neurodegeneration. The present work aimed to summarize the literature about the neuroprotective effect of QUR using known database sources. Besides, this review focuses on the assessment of the potential utilization of QUR as a complementary or alternative medicine for preventing and treating neurodegenerative diseases. An up-to-date search was conducted in PubMed, Science Direct and Google Scholar for published work dealing with the neuroprotective effects of QUR against neurotoxic chemicals or in neuronal injury, and in the treatment of neurodegenerative diseases. Findings suggest that QUR possess neuropharmacological protective effects in neurodegenerative brain disorders such as Alzheimer’s disease, Amyloid β peptide, Parkinson’s disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. In summary, this review emphasizes the neuroprotective effects of QUR and its advantages in being used in complementary medicine for the prevention and treatment o of different neurodegenerative diseases.

Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro.

The AMPK/PGC-1α pathway-mediated mitochondrial dysfunction has been supposed to play a crucial role in pathogenesis of diabetic peripheral neuropathy (DPN). The present study investigated the neuroprotective potential of quercetin, a natural AMPK activator. Streptozotocin (STZ)-induced diabetic rats that developed DPN phenotype were orally administrated with quercetin (30 and 60 mg/kg per day) for 6 weeks. The morphologic changes in the sciatic nerves (SN), the pathological structure of neurons in dorsal root ganglion (DRG), and the expressions of myelin proteins were assessed. The ATP content and the mitochondrial ultrastructure were measured. Furthermore, key proteins in the AMPK/PGC-1α pathway were determined. As a result, quercetin administration at both doses improved the paw withdrawal threshold, nerve conduction velocity, and the pathologic changes in SN and DRG of DPN rats. The expressions of myelin basic protein and myelin protein zero were also increased by quercetin. The oxidative stress, decreased ATP generation, and morphological changes of mitochondria were corrected by quercetin. In vitro study found that quercetin treatment significantly decreased the high-glucose-induced generation of reactive oxygen species, as well as attenuated the mitochondrial morphologic injuries and oxidative DNA damages of RSC96 cells. Quercetin treatment promoted the expressions of phosphorylated AMPK, PGC-1α, SIRT1, NRF1, and TFAM under hyperglycemic state in vivo and in vitro. This study revealed that the neuroprotective effect of quercetin was mainly related to mitochondrial protection by activation of the AMPK/PGC-1α pathway for the first time and proved quercetin as a potential therapeutic agent in the management of diabetic neuropathy.

Quercetin alleviates styrene oxide-induced cytotoxicity in cortical neurons in vitro via modulation of oxidative stress and apoptosis

Styrene 7,8-oxide (SO) is the principal metabolite of styrene, an industrial neurotoxic compound which causes various neurodegenerative disorders. The present study aimed to explore the mechanisms of SO cytotoxicity (0.5 − 4 mM) in primary cortical neurons and to evaluate the neuroprotective potential of quercetin (QUER). Our results showed that exposure to SO decreased viability of cortical neurons in a concentration-dependent manner. In the presence of QUER, cell viability was increased significantly. The neuroprotective effects of QUER were associated with the reduction of intracellular Reactive Oxygen Species (ROS), the decrease in calcium overload and the restoration of mitochondrial membrane depolarization caused by SO. Additionally, to evaluate neuronal death mechanisms triggered by SO, cells were incubated with Ac-DEVD-CHO, Calpeptin and Necrostatin-1, pharmacological inhibitors of caspase-3, calpains and necroptosis respectively. The data showed that the three inhibitors reduced cell death induced by SO and suggested the implication of apoptotic, necrotic and necroptotic pathways. However, western blot analysis showed that QUER attenuated the activation of caspase-3 but did not prevent calpain activity. Taken together, these data indicated that the cytotoxicity of SO was mediated by oxidative stress and apoptosis, necrosis and necroptosis mechanisms, while the neuroprotection provided by QUER against SO depended mainly on its anti-apoptotic activity.

Neuroprotective Effects of Quercetin in Pediatric Neurological Diseases.

Oxidative stress is a crucial event underlying several pediatric neurological diseases, such as the central nervous system (CNS) tumors, autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Neuroprotective therapy with natural compounds used as antioxidants has the potential to delay, ameliorate or prevent several pediatric neurological diseases. The present review provides an overview of the most recent research outcomes following quercetin treatment for CNS tumors, ASD and ADHD as well as describes the potential in vitro and in vivo ameliorative effect on oxidative stress of bioactive natural compounds, which seems like a promising future therapy for these diseases. The neuroprotective effects of quercetin against oxidative stress can also be applied in the management of several neurodegenerative disorders with effects such as anti-cancer, anti-inflammatory, anti-viral, anti-obesity and anti-microbial. Therefore, quercetin appears to be a suitable adjuvant for therapy against pediatric neurological diseases.

Neuroprotective effects of quercetin 3-O-sophoroside from Hibiscus rosa-sinensis Linn. on scopolamine-induced amnesia in mice

Abstract Quercetin 3-O-sophoroside (Q3OS) was isolated and identified from Hibiscus rosa-sinensis Linn. (HRS) for the first time. Although Q3OS is common glycosides, its therapeutic potential and mechanism of action against Alzheimer’s disease (AD) have rarely been reported. The results demonstrated that Q3OS treatment effectively ameliorated learning and memory impairment in mice with scopolamine (SCOP)-induced cognitive dysfunction by using the Morris water maze test. Nissl staining results revealed that Q3OS administration blocked neuronal loss in the hippocampal CA1 region. Immunohistochemistry and western blot results also indicated that Q3OS reversed the SCOP-induced decrease in ChAT expression, increase in AChE expression, and decrease in ACh. These findings suggested that Q3OS from HRS could be potentially used to prevent and treat AD, by exerting neuroprotective effects and these effects could be in response to its modification of the cholinergic system function. HRS can be potentially used as a neuroprotective nutrient in the prevention of AD.

Dietary quercetin attenuates depressive-like behaviors by inhibiting astrocyte reactivation in response to stress

The mechanisms underlying the antidepressant activity of quercetin are unknown. We investigated the effect of a quercetin-enriched diet (2 g/kg and 0.5 g/kg doses) on chronic social defeat stress (CSDS)-induced depressive-like behaviors in mice. The 2 g/kg quercetin-enriched diet attenuated depressive-like behaviors when introduced before CSDS (long-term). The long-term 0.5 g/kg quercetin-enriched diet showed a trend toward behavioral improvement. The frequencies of spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs) in the mPFC and hippocampus were significantly higher in mice fed the long-term 2 g/kg quercetin-enriched diet compared with the normal diet; no difference was found in the amygdala. Quercetin-enriched diets administered concurrently and after stress induction failed to trigger these effects. A1-specific astrocyte reactivity was markedly suppressed in the microglia and astrocytes isolated from the mPFC and hippocampus of mice fed the long-term quercetin-enriched diet, but not in those who received quercetin supplementation concurrently or after CSDS. To confirm the role of astrocytes in the neuroprotective effect of quercetin, we activated astrocytes by injecting a chemogenic AAV stimulus into the mPFC and hippocampus and found that astrocyte activation during administration of the long-term quercetin-enriched diet significantly deceased the frequency of sEPSCs and sIPSCs in the mPFC and hippocampus and further attenuated quercetin-induced behavioral improvements. These findings highlight the key role of astrocyte reactivation in the regulation of quercetin neuroprotective activity and suggest that a diet high in quercetin, whether as a fruit- and vegetable-rich diet or food additive may help cope with stress.

Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation.

Microglia stimulated by oxygen glucose deprivation (OGD) were treated with quercetin to investigate the effect on oxidative stress and the inflammatory response and to explore whether toll-like receptor 4 (TLR4) signaling was involved. In addition, the effect of quercetin on the neurological functions of neonatal mice with hypoxic-ischemic brain injury (HIBI) was examined. Mouse BV2 microglial cells and postnatal day 7 neonatal mice were used. A predetermined concentration of quercetin was used in cell experiments. Quercetin was injected i.p. (50mg/kg) at three time points after HI insult: 0, 24, and 48h. Cell viability assay, Western blotting, qRT-RCR, ELISA, HIBI model construction and behavioral tests. This study first showed that quercetin protected BV2 cells from OGD-induced damage and reversed the changes in microglial oxidative stress-related molecules. Second, quercetin inhibited OGD-induced expression of inflammatory factors in BV2 cells and suppressed TLR4/MyD88/NF-κB signaling. Finally, quercetin was disclosed to be effective in mitigating cerebral infarct volume and cognitive and motor function deficits in HIBI mice. These results suggest that the neuroprotective effect of quercetin in HIBI mice is partially due to the inhibition of oxidative stress and TLR4-mediated inflammatory responses in activated microglia.