Protective Role Of Quercetin Research Articles

The protective role of quercetin against copper-induced female reproductive toxicity: Insights from transcriptome analysis

Quercetin has been shown to mitigate the cytotoxic effects of heavy metals. While copper is an essential trace element for bodily functions, excessive intake has been linked to impaired female reproductive function. Transcriptome analysis was employed to identify genes that are differentially expressed in response to high copper and were validated through qRT-PCR and western blotting. ATP content and Tunel were used to identify the damage of mitochondrial and cell apoptosis. PPI analysis revealed that MKI67, TOPII, ASPM, CASP3, PLK1, and TTK are central proteins within the network. Additionally, exposure to elevated levels of copper resulted in the dysregulation of 86 genes associated with mitochondria. Conversely, treatment with quercetin (QUE) in combination with high copper led to the normalization of 42 mitochondria-related genes previously affected by high copper levels. Furthermore, CuSO4 decreases ATP content and induces cell apoptosis, which can be reversed by QUE. Results suggest that elevated copper levels could lead to oxidative stress and apoptosis by inducing mitochondrial damage, while QUE has the potential to mitigate these effects, ultimately safeguarding granulosa cells and halting the progression of cell death. This study provides novel insights into the molecular pathways involved in female reproductive toxicity caused by excessive copper exposure.

Protective Role of Quercetin on Carmustine-induced Lung Toxicity in Adult Male Albino Rats

Background: Carmustine (BCNU) is an alkylating agent used as an antineoplastic agent. A major problem with the clinical use of BCNU is the occurrence of pulmonary toxicity. Quercetin (QUE) is an important polyphenolic flavonoid that exhibits antioxidant, anti-inflammatory and other health-promoting effects. This study aimed to investigate the protective effect of QUE on BCNU-induced lung injury in rats using histologic and biochemical methods. Methods: Forty adult male albino rats were divided into 4 groups: Group I served as the control group. Group ІІ received QUE orally in a dose of 100 mg/kg per day for 7 days. Group ІІI received a single dose (30 mg/kg) of BCNU intraperitoneally (i.p.) on the 7th day of the study. Group ІV received (BCNU + QUE). On the 8th day of the experiment, lung tissues were collected for histopathological examinations. The levels of malondialdehyde (MDA), hydroxyproline (HYP), myeloperoxidase (MPO), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were also determined in all dissected tissues. Results: Pretreatment with QUE ameliorated lung morphological changes noticed in the BCNU group and the levels of MDA, HYP, and MPO were significantly decreased whereas those of GSH, GSH-Px, and SOD were significantly increased. Conclusions: QUE provides a protective effect against BCNU-induced lung injury by reducing oxidative stress and pulmonary fibrosis.

Dietary quercetin intake is associated with lower ulcerative colitis risk but not Crohn's disease in a prospective cohort study and in vivo experiments.

Objectives: Previous preclinical evidence indicates a protective role of quercetin against inflammatory bowel disease (IBD). However, there is no evidence from human populations, resulting in knowledge gaps regarding the role of quercetin in the IBD development. We aimed to prospectively evaluate the associations between dietary quercetin intake and IBD in humans and in vivo animal models. Methods: We included 187 709 IBD-free participants from the UK Biobank. Dietary information was collected using validated 24-hour dietary recalls and the quercetin intake was estimated based on national nutrient databases. Incident IBD was ascertained via inpatient and primary care data. Cox proportional hazard models were used to estimate the multi-variable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Experiments were conducted in two chemical-induced (dextran sulfate sodium salt and trinitro-benzene-sulfonic acid) mouse models orally pretreated with quercetin (CAS number: 117-39-5) solution to evaluate the effects of quercetin at physiological levels. Results: After a mean follow-up of 9.7 years, we documented 863 incident IBD. Compared to participants with the lowest quintile intake of quercetin, those in the highest quintiles were associated with a lower risk of IBD (aHR 0.76, 95% CI 0.60-0.95; P-trend = 0.004) and ulcerative colitis (aHR 0.69, 95% CI 0.53-0.91; P-trend = 0.001), but not Crohn's disease (aHR 0.95, 95% CI 0.62-1.45; P-trend = 0.765). Mouse models showed that pretreatment with quercetin could attenuate the chemically induced colitis. Conclusions: Higher quercetin intake was associated with a lower risk of IBD, especially UC. The protective role of quercetin is promising in humans and warrants further investigation into downstream mechanisms.

Quercetin influences intestinal dysbacteriosis and delays alveolar epithelial cell senescence by regulating PTEN/PI3K/AKT signaling in pulmonary fibrosis

Pulmonary fibrosis is a chronic and progressive lung disease with high mortality. This study aims to explore the protective mechanism of quercetin against pulmonary fibrosis regarding cell senescence and gut microbiota. Rats were intratracheally injected with bleomycin (BLM) to establish a pulmonary fibrosis rat model. RLE-6TN cells were stimulated with BLM to build the model of alveolar epithelial cell senescence, and RLE-6TN-derived conditional medium (CM) was harvested to further culture fibroblasts. Histopathological changes were assessed by H&E and Masson staining. α-SMA expression was assessed by immunofluorescence assay. Senescence-associated β-galactosidase (SA-β-gal) staining and senescence-associated secretory phenotype (SASP) cytokine assay were conducted to assess cellular senescence. Gut microbiota was analyzed by 16S rRNA gene sequencing. The fibrosis-, senescence-, and PTEN/PI3K/AKT signaling–related proteins were examined by western blot. In BLM-induced pulmonary fibrosis rats, quercetin exerted its protective effects by reducing histological injury and collagen deposition, lessening cellular senescence, and regulating gut microbiota. In BLM-induced alveolar epithelial cell senescence, quercetin inhibited senescence, lessened SASP cytokine secretion of alveolar epithelial cells, and further ameliorated collagen deposition in fibroblasts. In addition, quercetin might exert its functional effects by regulating the PTEN/PI3K/AKT signaling pathway. Moreover, quercetin regulated intestinal dysbacteriosis in BLM-induced pulmonary fibrosis rats, especially boosting the abundance of Akkermansia. To conclude, our findings provide an in-depth understanding of the potential mechanism behind the protective role of quercetin against pulmonary fibrosis.

Quercetin alleviates zearalenone-induced apoptosis and necroptosis of porcine renal epithelial cells by inhibiting CaSR/CaMKII signaling pathway

Zearalenone (ZEA) is a mycotoxin that is highly contaminated in feed and can cause severe toxic effects on the kidneys and other organs of animals. Quercetin (QUE) is a plant-derived flavonoid with a variety of detoxification properties, but the mechanism by which QUE detoxifies the toxic effects induced by ZEA has not yet been fully elucidated. We treated porcine kidney cells (PK15) with 80 μM ZEA and/or 30 μM QUE. The results showed that ROS and MDA levels were increased, antioxidant system levels were down-regulated, anti-apoptotic factor expression levels were decreased, and apoptotic and necroptosis-related factors were up-regulated after ZAE exposure. In addition, the results of Ca2+ staining, mitochondrial membrane potential, and mitochondrial dynamics-related indicators showed that ZEA induced Ca2+ overload in PK15 cells and increased mitochondrial Ca2+ uptake (MCU expression increased). The accumulated ROS and free Ca2+ further aggravate mitochondrial damage and eventually lead to mitochondrial pathway apoptosis and necroptosis. Nevertheless, QUE targets CaSR to inhibit the CaSR/CaMKII pathway and regulate calcium homeostasis, thereby alleviating apoptosis and necroptosis mediated by mitochondrial dynamic disorder and dysfunction. The present study demonstrated the mechanism by which ZEA induces apoptosis and necroptosis in PK15 and the protective role of QUE in this process.

Discovering the Protective Effects of Quercetin on Aflatoxin B1-Induced Toxicity in Bovine Foetal Hepatocyte-Derived Cells (BFH12).

Aflatoxin B1 (AFB1) induces lipid peroxidation and mortality in bovine foetal hepatocyte-derived cells (BFH12), with underlying transcriptional perturbations associated mainly with cancer, cellular damage, inflammation, bioactivation, and detoxification pathways. In this cell line, curcumin and resveratrol have proven to be effective in mitigating AFB1-induced toxicity. In this paper, we preliminarily assessed the potential anti-AFB1 activity of a natural polyphenol, quercetin (QUE), in BFH12 cells. To this end, we primarily measured QUE cytotoxicity using a WST-1 reagent. Then, we pre-treated the cells with QUE and exposed them to AFB1. The protective role of QUE was evaluated by measuring cytotoxicity, transcriptional changes (RNA-sequencing), lipid peroxidation (malondialdehyde production), and targeted post-transcriptional modifications (NQO1 and CYP3A enzymatic activity). The results demonstrated that QUE, like curcumin and resveratrol, reduced AFB1-induced cytotoxicity and lipid peroxidation and caused larger transcriptional variations than AFB1 alone. Most of the differentially expressed genes were involved in lipid homeostasis, inflammatory and immune processes, and carcinogenesis. As for enzymatic activities, QUE significantly reverted CYP3A variations induced by AFB1, but not those of NQO1. This study provides new knowledge about key molecular mechanisms involved in QUE-mediated protection against AFB1 toxicity and encourages in vivo studies to assess QUE's bioavailability and beneficial effects on aflatoxicosis.

Protective effect of quercetin on fetal development and congenital skeletal anomalies against exposure of pregnant Wistar rats to crude oil vapor.

Epidemiological evidence indicates a relationship between maternal exposure to crude oil vapors (COV) during pregnancy and adverse pregnancy outcomes. Quercetin (QUE) is a plant flavonoid with purported antioxidant and anti-inflammatory effects, which has been shown to prevent birth defects. This study was aimed to investigate the protective role of QUE on fetal development and congenital skeletal anomalies caused by exposure of pregnant rats to COV. Twenty-four pregnant Wistar rats were randomly categorized into four groups of control, COV, COV + QUE, and QUE (50 mg/kg). The inhalation method was used to expose pregnant rats to COV from day 0 to 20 of pregnancy, and QUE was administered orally during this period. On day 20 of gestation, the animals were anesthetized and a laparotomy was performed, and then the weight and crown rump length (CRL) of the fetuses were determined. Skeletal stereomicroscopic evaluations of fetuses were performed using Alcian blue/Alizarin red staining method, and the expression of osteogenesis-related genes (Runx2 and BMP-4) was evaluated using qPCR. This study showed that prenatal exposure to COV significantly reduced fetal weight and CRL, and expression of Runx2 and BMP-4 genes. Moreover, COV significantly increased the incidence of congenital skeletal anomalies such as cleft palate, spina bifida and non-ossification of the fetal bones. However, administration of QUE with exposure to COV improved fetal bone development and reduced congenital skeletal anomalies. QUE can ameliorate the teratogenic effects of prenatal exposure to COV by increasing the expression of osteogenesis-related genes.

Protective role of quercetin and kaempferol against oxidative damage and photosynthesis inhibition in wheat chloroplasts under arsenic stress.

Arsenic (As) toxicity negatively impacts plant development, limits agricultural production, and, by entering the food chain, endangers human health. Studies on the use of natural and bioactive molecules in increasing plants' resistance to abiotic stressors, such as As, have gained increasing attention in the last few years. Flavonols are plant secondary metabolites with high potential in stress tolerance due to their roles in signal transmission. Therefore, the focus of this study was to examine the effects of two flavonols, quercetin (Q, 25 μM) and kaempferol (K, 25 μM), on growth parameters, photosynthesis, and chloroplastic antioxidant activity in wheat leaves under As stress (100 μM). As stress reduced the relative growth rate by 50% and relative water content by 25% in leaves. However, applying Q and/or K alleviated the As-induced suppression of growth and water relations. Exogenous phenolic treatments reversed the effects of As toxicity in photochemistry and maintained the photochemical quantum efficiency of the Photosystem II (Fv /Fm ). As exposure increased, the H2 O2 content in wheat chloroplasts by 42% and high levels of H2 O2 accumulation were also observed in guard cells in confocal microscopy images. Analysis of the chloroplastic antioxidant system has shown that Q and K applications increase the activity of antioxidant enzymes, including superoxide dismutase, peroxidase, and ascorbate peroxidase. Phenolic applications have induced the ascorbate-glutathione (AsA-GSH) cycle in charge of the protection of the cellular redox balance in different ways. It has been determined that Q triggers the AsA renewal, and K maintains the GSH pool. As a result, Q and K applications provide tolerance to wheat plants under As stress by increasing the chloroplastic antioxidant system activity and protecting photosynthetic reactions from oxidative damage. This study reveals the potential use of plant phenolic compounds in agricultural systems as a biosafe strategy to enhance plant stress tolerance, hence increasing yield.

Elucidating the toxicity mechanism of AFM2 and the protective role of quercetin in albino mice

Aflatoxin M2 (AFM2) is a type of mycotoxin detected in milk or dairy products from animals consuming contaminated feed. In this study, the toxicity mechanism of AFM2 and the protective effects of quercetin were investigated in albino mice. For this purpose, the mice were divided into 6 groups and the groups were fed with quercetin and AFM2. The toxic effects of AFM2 and the protective properties of quercetin were investigated using physiological, biochemical and cytogenetic parameters. The genotoxic mechanism of AFM2 and the protective role of quercetin were investigated by molecular docking, which is an in silico model. As a result, 16 mg/kg b.w AFM2 administration caused serious changes in body weight, organ index, kidney and liver weight, and deterioration of antioxidant/oxidant balance in liver and kidney organs. The decrease in glutathione levels along with an increase in malondialdehyde (MDA) levels in the liver and kidney after AFM2 administration indicates that oxidative stress is induced. The increases in alanine transaminase (ALT) and aspartat transaminase (AST) levels, which are indicators of liver damage, and the increases in serum levels of blood urea nitrogen (BUN) and creatinine, which are indicators of kidney damage, confirm the damage in both organs. AFM2 also caused genotoxicity by inducing micronucleus (MN) and chromosomal abnormalities (CAs) in bone marrow tissue. It has been determined that AFM2, which exhibits genotoxicity as a result of its clastogenic and aneugenic effects, causes CAs by interacting with DNA. Quercetin provided significant protection by improving liver and kidney tissues, partial normalization in serum parameter levels, and severe reductions in MN and CAs. The highest protection was determined as 74.1% against dicentric chromosome formations in 50 mg/kg b.w quercetin application. The interaction of quercetin with xanthine oxidase and nitric oxide synthase enzymes was determined in silico with an inhibition constant in the range of 283.71–476.17 nM. These interactions cause changes in the activity of enzymes, reducing the oxidative load in the cell, and in this way, quercetin provides protection. All toxic effects induced by AFM2 were decreased with quercetin administration dose-dependently, and this protective effect was associated with quercetin's reduction of oxidative load by inhibiting the free radical-producing enzyme. All toxic effects caused by AFM2 were decreased with quercetin administration in a dose-dependent manner, and this protective effect was associated with quercetin's reduction of oxidative load by inhibiting the enzyme that produces free radicals.

Protective Role of Quercetin on Thioacetamide-Induced Renal Injury in Adult Male Albino Rats

Background: Thioacetamide (TAA) is a recognized industrial poisonous agent drastically used in animal studies for induction of hepatic necrosis, fibrosis and cirrhosis. It is additionally reported to be nephrotoxic through induction of oxidative stress. Quercetin (QE) has a high antioxidant capacity via free radical scavenging, transition metal ion binding, and lipid peroxidation inhibition. Aim of the work: The goal of this research was to see if QE may help reduce the negative effects of thioacetamide on renal tissue by histological examination of the kidney. Material and methods: Twenty four adult male Albino rats 7–9 weeks old around 180–200g body weight were allocated into 3 groups; Group I (n=8) receiving distilled water, Group II (n=8); rats receiving TAA and Group III (n=8); receiving TAA and QE. Results: Renal tissues were examined under a light microscope stained by Harris Hematoxylin & Eosin (H&E stain), Periodiceeacid Schiff (PAS) andjMasson’srTrichrome for TAA-treated groups revealed severe histopathological changes, whereas specimens obtained from QE-treated groups showed onlywmild changes. Immunohistochemical results corroborated these findings. Conclusion: This study demonstrated the ameliorative consequences of QE in opposition to TAA-induced renal injury in rats. The result of this study might contribute in the development of a novel complementary alternative medication in combating and therapeutic intervention of TAA-induced renal injury. KEY WORDS: Thioacetamide, renal, quercetin, albino rat and histopathology.

Potential protective effect of quercetin on the male reproductive system against exposure of Wistar rats to crude oil vapor: Genetic, biochemical, and histopathological evidence

Toxic compounds in crude oil vapor (COV), including polycyclic aromatic hydrocarbons (PAHs), are associated with adverse effects on reproduction in living organisms. Quercetin (QT) is the most plentiful flavonoid in vegetables and fruits, with antioxidant activities. This study aimed to evaluate the protective role of QT on testicular toxicity induced by COV. Twenty-four adult male Wistar rats were randomly divided into four groups (n = 6) including control, quercetin (QT) (50 mg/kg), crude oil vapors (COV), and COV + QT. The inhalation method was used to expose the rats to crude oil vapors for 5 h daily, and QT was administered orally. After 30 days, the rats were euthanized, then, the testes were removed for gonadosomatic index (GSI), sperm parameters, H&E staining, the activity of the antioxidant enzymes, and apoptotic gene expression assessments. The COV statistically significantly (P < 0.05) reduced GSI, sperm count, motility, viability, and sperm normal morphology, histological indexes, and antioxidant enzyme activities than control. Also, COV statistically significantly (P < 0.05) increased the expression of caspase-3, p-53, and Bax genes and decreased Bcl-2 gene expression. Co-administration of QT + COV caused a statistically significant (P < 0.05) decrease in Bax gene expression and increased antioxidant enzyme activities, Bcl-2 gene expression, and reproductive parameters than the COV group. Based on the results of this study, it appears that crude oil vapor causes side effects on male reproduction. Yet, quercetin has the potential to reduce the side effects of crude oil vapor on the male reproductive system.

Nicotine exacerbates reproductive biomarkers via generation of free radicals in female Wistar rats: Protective role of Quercetin

Background: Nicotine has been widely reported to generate free radicals in several organs of the body. Therefore, this study investigated the ameliorative potentials of Quercetin on selected reproductive biomarkers in female Wistar rats.Methods: Forty female rats were randomly divided into five groups (n=8) which were treated as follows: Group I (CN) received normal saline (1 ml/kg bwt); Group II (LN) received nicotine (0.5 mg/kg bwt) only; Group III (HN) received nicotine (1.0 mg/kg bwt) only; however, Groups IV (LNA) and V (HNA) received 0.5 and 1.0 mg/kg of nicotine with 20 mg/kg of quercetin respectively. All administration were done orally and lasted 28 days. Results: Nicotine significant reduction in the bioavailability of estrogen and progesterone in the treated rats when compared to control. Furthermore, relative to the control group, nicotine administration resulted in significant elevation in MDAand consequently caused significant reduction in the antioxidant enzymes (SOD and CAT) activities. However, quercetin treatment ameliorated these alterations. Conclusion: Quercetin dampens the reproductive distruptive effects exerted by nicotine through anti-oxidative mechanism in female Wistar rats.

Protective Role of Quercetin in Carbon Tetrachloride Induced Toxicity in Rat Brain: Biochemical, Spectrophotometric Assays and Computational Approach.

Carbon tetrachloride (CCL4) induces oxidative stress by free radical toxicities, inflammation, and neurotoxicity. Quercetin (Q), on the other hand, has a role as anti-inflammatory, antioxidant, antibacterial, and free radical-scavenging. This study explored protection given by quercetin against CCL4 induced neurotoxicity in rats at given concentrations. Male Wistar rats were divided into four groups Group C: control group; Group CCL4: given a single oral dose of 1 mL/kg bw CCL4; Group Q: given a single i.p injection of 100 mg/kg bw quercetin; and Group Q + CCL4: given a single i.p injection of 100 mg/kg bw quercetin before two hours of a single oral dose of 1 mL/kg bw CCL4. The results from brain-to-body weight ratio, morphology, lipid peroxidation, brain urea, ascorbic acid, reduced glutathione, sodium, and enzyme alterations (aspartate aminotransferase (AST), alanine aminotransferase (ALT), catalase, and superoxide dismutase) suggested alterations by CCL4 and a significant reversal of these parameters by quercetin. In silico analysis of quercetin with various proteins was conducted to understand the molecular mechanism of its protection. The results identified by BzScore4 D showed moderate binding between quercetin and the following receptors: glucocorticoids, estrogen beta, and androgens and weak binding between quercetin and the following proteins: estrogen alpha, Peroxisome proliferator-activated receptors (PPARγ), Herg k+ channel, Liver x, mineralocorticoid, progesterone, Thyroid α, and Thyroid β. Three-dimensional/four-dimensional visualization of binding modes of quercetin with glucocorticoids, estrogen beta, and androgen receptors was performed. Based on the results, a possible mechanism is hypothesized for quercetin protection against CCL4 toxicity in the rat brain.

The Possible Protective Role of Quercetin on Nicotine Induced Liver and Kidney Damage of Neonates Albino Rats: Histological and Immunohistochemical Study

The Possible Protective Role of Quercetin on Nicotine Induced Liver and Kidney Damage of Neonates Albino Rats: Histological and Immunohistochemical Study

Protective Role of Quercetin Against Rotenone- Induced Hepato and Nephrotoxicity in Swiss Albino Mice

Rotenone is well known environmental neurotoxin used to induce Parkinson’s disease (PD) model. Numerous studies are investigated its toxicity on the brain but few studies are available that examined its toxicity on the liver and kidney. Therefore, the main aim of the present work was to explore the toxicity of rotenone on the liver and kidney and its protection through quercetin. Administration of rotenone orally at the dose of (5mg/kg b.w daily for 60 days) caused a significant increase in the levels of liver function and renal function biomarkers as compared to controls. A significant increase in the level of lipid peroxidation, nitric oxide, and decrease in the levels of reduced glutathione, reduction in the activities of catalase and superoxide dismutase were observed in the liver and kidney as compared to control. The histopathological and SEM study in rotenone-treated mice showed alteration and signs of inflammation in the liver and kidney. While co-treatment of quercetin orally (30 mg/kg b.w for 60 days) together with rotenone, reversed the above parameters. In conclusion, rotenone significantly damages the liver and kidney, and the administration of quercetin along with rotenone shown a protective role. This study provides a new insight into where rotenone-induced liver and kidney dysfunction could be successfully protected by quercetin.

The probable protective Effect of Quercetin Against Doxorubicin-Induced Hepatotoxicity in Adult Albino Rats: A Biochemical and Immunohistopathological Study

Background: Doxorubicin (DOX) is an anthracycline antineoplastic which causes hepatotoxicity by induction of free radicals and inflammatory liver tissues. Quercetin (QCT) is considered as a potent antioxidant that may ameliorates hepatotoxicity. Aim of the work: The current study was designed to detect the toxic effects of DOX in liver cells and evaluating the possible protective role of QCT against those toxic alterations in adult male albino rats. Materials and methods: 40 male albino rates were divided to four groups: Control (group I), DOX-treated (group II): Rats received 18 mg/kg of body weight of DOX. Group III, received 60 ml/kg of QCT combined with DOX. Group IV treated with DOX plus 100 ml of QCT/kg. After rate sacrifice, liver enzymes and the bile levels were estimated. The livers were extracted and used in oxidative stress markers, histological and immunological studies. Results: Doxorubicin administration induced an increase in liver enzymes, bile level and oxidative stress markers. QCT administration induced an improvement in those levels, especially with the high dose. The microscopic examinations of the DOX-treated sections showed loss of normal architectures of hepatic cells, enlargement and congestion of the central and portal veins and blood sinusoids, vacuolar degeneration, cholelithiasis and necrosis of H&E stained hepatocytes. PAS-stained liver sections in the DOX-treated group showed an increase in the depth of the stain. Quercetin administration improved these changes and hepatocytes which stained with PAS showed moderate to mild staining, especially with the high dose of QCT. Sections of the stained liver caspase-3, in DOX-treated group showed positive results with intensity. QCT treated groups showed little effects of caspase-3, especially with the high dose. Conclusion: DOX had toxic effects on rats’ livers, with significant improvement after treatment with QCT as an antioxidant substance, and its high doses were more protective than low doses.

Protective Effects of Quercetin against Rotenone Induced Histopathological and Biochemical Alteration in Testes of Mice

The present work aimed to investigate the protective role of quercetin against rotenone-induced testes damage at the level of oxidative stress and histological alteration. Reproductive toxicity was induced in mice by oral treatment of rotenone, 5 mg/kg body weight daily for 60 days, dissolve in sunflower oil as a vehicle. The quercetin was orally administered 30 mg/kg body weight daily for 60 days along with rotenone. The results of the current study showed that rotenone significantly reduced the Reduced glutathione (GSH) content and decreased the activities of Catalase (CAT) and Superoxide dismutase (SOD) and increased the oxidative markers such as Lipid peroxidation (LPO), and Nitric Oxide (NO) in rotenone treated group as compared to control. Co-administration of quercetin along with rotenone significantly reduced LPO and NO in the testes of mice when compared to rotenone alone group, increased the content of GSH, enhanced activities of CAT, and SOD when compared to rotenone the only group. The results of histological studies of the rotenone treated group showed a reduced number of germ cells, sperms loss, abnormality in seminiferous tubules, and degeneration of interstitial cells was found in the rotenone treated group as compared to control. While co-administration of quercetin reverses these adverse effects. The results of the current study clearly indicated that rotenone exerts harmful effects on the testes and co-administration of quercetin along with rotenone significantly protects damage caused by rotenone.

Quercetin Efficiently Alleviates TNF-α-Stimulated Injury by Signal Transducer and Activator of Transcription 1 and Mitogen-Activated Protein Kinase Pathway in H9c2 Cells: A Protective Role of Quercetin in Myocarditis.

This study aimed to evaluate the protective effect of quercetin and its in-depth mechanism in TNF-α-stimulated cardiomyocytes. The differential expression of TNF-alpha (TNF-α) and signal transducer and activator of transcription 1 (STAT1) was analyzed based on the GEO database. H9c2 cells were stimulated with TNF-α to simulate myocarditis. Cell counting kit-8 assay and flow cytometry assay were performed to detect the cell viability and apoptosis. ELISA was used to measure the levels of proinflammatory cytokines (IL-6 and IL-17A) and anti-inflammatory cytokine (IL-10). STAT1 expression was downregulated by transfection with si-STAT1, and its expression was detected using quantitative real-time polymerase chain reaction and Western blot. Western blot was also performed to assess the expression of the mitogen-activated protein kinase (MAPK) pathway-related factors. In this article, TNF-α was highly expressed in patients with myocarditis, and TNF-α (20 μg/mL) declined the viability of H9c2 cells. Quercetin pretreatment partially alleviated the decrease of cell viability, the increase of apoptosis, and the release of inflammatory cytokines (IL-10, IL-6, and IL-17A) induced by TNF-α. In addition, TNF-α increased STAT1 expression, but quercetin prevented the TNF-α-increased STAT1 level. Remarkably, knockdown of STAT1 enhanced the protective effect of quercetin on TNF-α-injured H9c2 cells. Moreover, quercetin restrained the TNF-α-induced activation of the MAPK pathway. Also, the inhibitory effect of quercetin on the pathway was aggravated by STAT1 lacking. In summing, quercetin plays a protective role in TNF-α-stimulated H9c2 cell injury, which may be related to the regulation of STAT1 and MAPK pathway.

Protective Role Of Quercetin On Hippocampus Inflammatory And Oxidative Damage Induced By Monosodium Glutamate In Rats

The aim of the current study was to investigate the possible protective role of quercetin against monosodium glutamate (MSG) induced oxidative stress and inflammation on the brain hippocampus of adult male albino rats. Thirty adult male albino rats were equally divided into 5 groups; Group I (control), group II received1 ml/ kg/ day of 0.5% of Dimethyl sulfoxide (DMSO), group III received 50 mg of quercetin/ kg/ day, group IV received1.6 g/ kg/ day of MSG, group V received quercetin and after one hour, rats received MSG as previously mentioned. All treatments were given orally for 8 weeks. Then rats were anesthetized, sacrificed and specimens from the brain hippocampus were taken for biochemical and histological studies. MSG exposure showed deleterious effects on Y-maze discrimination learning and memory, significantly increased tissue malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), interleukin- 1 beta (IL-1β), tumor necrosis factor-α (TNF-α), glutamate level and acetyl cholinesterase (AChE) activity with significant depletions of catalase (CAT) activities and reduced glutathione (GSH) content. This was accompanied with alteration in the structure of the brain hippocampus. Co-administration of quercetin along with MSG ameliorated the above mentioned effects. The results of this study have shown that quercetin has protective effects against MSG-induced toxicity in rat brain hippocampus.

Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats.

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1β, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.