Combination Of Quercetin Research Articles

Quercetin suppresses DNA double-strand break repair and enhances the radiosensitivity of human ovarian cancer cells via p53-dependent endoplasmic reticulum stress pathway.

Quercetin is proven to have anticancer effects for many cancers. However, the role of tumor suppressor p53 on quercetin’s radiosensitization and regulation of endoplasmic reticulum (ER) stress response in this process remains obscure. Here, quercetin exposure resulted in ER stress, prolonged DNA repair, and the expression of p53 protein; phosphorylation on serine 15 and 20 increased in combination with X-irradiation. Quercetin pretreatment could potentiate radiation-induced cell death. The combination of irradiation and quercetin treatment aggravated DNA damages and caused typical apoptotic cell death; as well the expression of Bax and p21 elevated and the expression of Bcl-2 decreased. Knocking down of p53 could reverse all the above effects under quercetin in combination with radiation. In addition, quercetin-induced radiosensitization was through stimulation of ATM phosphorylation. In human ovarian cancer xenograft model, combined treatment of quercetin and radiation significantly restrained the growth of tumors, accompanied with the activation of p53, CCAAT/enhancer-binding protein homologous protein, and γ-H2AX. Overall, these results indicated that quercetin acted as a promising radiosensitizer through p53-dependent ER stress signals.

BEHAVIORAL STUDIES OF WISTAR RATS IN ROTENONE INDUCED MODEL OF PARKINSON’S DISEASE

Objective: The objective of the study was to determine the behavioral activities of Wistar rats induced with rotenone. Methods: Thirty-six male Wistar rats were taken for the study and divided into six groups of six rats each. Group-I is the vehicle-treated, Group–II animals were induced with rotenone (3 mg/kg/bwt) by i. p. Group-III were co-treated with rotenone and L-DOPA (10 mg/kg/bwt) orally, Group-IV were co-treated with rotenone and quercetin (25 mg/kg/bwt) orally, Group-V were co-treated with rotenone and hesperidin (50 mg/kg/bwt) orally, Group-VI were treated with rotenone, quercetin and hesperidin in the same dosage regime for 60 d. The behavioural tests, such as open field test, ladder climbing test and hanging wire test were performed. The biochemical parameters such as urea, creatinine and activities of ALT and AST were also analysed.Results: All data are expressed as the mean±SD. Disability was noted in the behaviour of rats induced with Parkinson’s disease (PD). The deficits in behavioral activity were significantly changed when compared with an induced group (p<0.001) and biochemical parameters due to rotenone were significantly (p<0.001) restored by co-treatment with quercetin and hesperidin.Conclusion: In our in vivo study, we have demonstrated the combination of quercetin and hesperidin to serve as neuroprotective compounds by improving the behavioral abnormalities and restoring the biochemical parameters. Hence, these powerful antioxidants may protect brain cells.

Piperine in combination with quercetin halt 6-OHDA induced neurodegeneration in experimental rats: Biochemical and neurochemical evidences

Parkinson’s disease (PD) is a multifactorial neurological disorder caused by selective dopaminergic neuronal loss. Quercetin (QC) in combination with piperine (bioenhancer) acts as potential antioxidant, anti-inflammatory and neuroprotective against 6-OHDA rat model of PD. Rats were injected 6-OHDA (8μg/2μl, saline) unilaterally, intranigrally once into right SNpc. Pre-treatment with QC (25 and 50mg/kg, p.o.) alone and combination of QC (25mg/kg, p.o.) with piperine (2.5mg/kg, p.o.) were given for 14days starting from 8th day of 6-OHDA infusion. Post lesions were confirmed by rotational behavior with amphetamine (2.5mg/kg, i.p.) and motor coordination was assessed by narrow beam walk, open field and rotarod apparatus on the weekly basis. On 22nd day, animals were sacrificed and striatum homogenates were used for biochemical (LPO, GSH, Nitrite), neuroinflammatory (TNF-α, IL-1 β and IL-6) and neurotransmitter (dopamine, norepinephrine, serotonin, GABA, glutamate) analysis. Rats pre-treated with QC alone and in combination with piperine have significantly attenuated the 6-OHDA induced rotational behavior and motor deficits. Further, these drugs have significantly improved antioxidant potential, decreased striatal proinflammatory cytokines level as well as restored neurotransmitters level. The neuroprotective enhancement of QC along with piperine is attributed through antioxidant, anti-inflammatory and preventing neurotransmitter alteration mechanisms.

Dietary Flavonoids and Acarbose Synergistically Inhibit α-Glucosidase and Lower Postprandial Blood Glucose.

The inhibition of porcine pancreatic α-amylase and mammalian α-glucosidase by 16 individual flavonoids was determined. The IC50 values for baicalein, (+)-catechin, quercetin, and luteolin were 74.1 ± 5.6, 175.1 ± 9.1, 281.2 ± 19.2, and 339.4 ± 16.3 μM, respectively, against α-glucosidase. The IC50 values for apigenin and baicalein were 146.8 ± 7.1 and 446.4 ± 23.9 μM, respectively, against α-amylase. The combination of baicalein, quercetin, or luteolin with acarbose showed synergistic inhibition, and the combination of (+)-catechin with acarbose showed antagonistic inhibition of α-glucosidase. The combination of baicalein or apigenin with acarbose showed additive inhibition of α-amylase at lower concentrations and antagonistic inhibition at a higher concentration. Kinetic studies of α-glucosidase activity revealed that baicalein alone, acarbose alone, and the combination showed noncompetitive, competitive, and mixed-type inhibition, respectively. Molecular modeling revealed that baicalein had higher affinity to the noncompetitive binding site of maltase, glucoamylase, and isomaltase subunits of α-glucosidase, with glide scores of -7.64, -6.98, and -6.88, respectively. (+)-Catechin had higher affinity to the active sites of maltase and glucoamylase and to the noncompetitive site of isomaltase. After sucrose loading, baicalein dose-dependently reduced the postprandial blood glucose (PBG) level in mice. The combination of 80 mg/kg baicalein and 1 mg/kg acarbose synergistically lowered the level of PBG, and the hypoglycemic effect was comparable to 8 mg/kg acarbose. The results indicated that baicalein could be used as a supplemental drug or dietary supplement in dietary therapy for diabetes mellitus.

Protective effect of quercetin on bupivacaine-induced neurotoxicity via T-type calcium channel inhibition

Purpose: To determine the effect of quercetin on bupivacaine-induced neurotoxicity and to investigate the mechanisms involved. Methods: Cultured SH-SY5Y cells were divided into five treatment groups: control group with no drug, bupivacaine treatment group, quercetin group, bupivacaine--quercetin combination treatment group, and bupivacaine-mibefradil combination treatment group. Cell morphology in each group was examined by microscopy while cell viability was assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2- tetrazolium bromide (MTT) assay after 24 h incubation. Cytosolic calcium ion concentration was determined by flow cytometry while Cav3.1 protein expression was evaluated by western blot. Results: Quercetin (50 μM) significantly ( p < 0.05) protected SH-SYS5 cells from bupivacaine-induced cell apoptosis and also significantly reduced intracellular calcium ion concentration ( p < 0.01) by approximately 40 %. Cav3.1 protein expression was normalized following quercetin treatment. Conclusion: These results show that quercetin reduces the neurotoxicity induced by bupivacaine, possibly through inhibition of T-type calcium channel. This finding implies a novel mechanism for neuroprotective effect of quercetin, and its potential for treating toxicity arising from the use of local anesthetic agents. Keywords: Quercetin, Bupivacaine, Local anaesthetic, Neuroprotection, Neurotoxicity, T-type calcium channel

Combination of quercetin, cinnamaldehyde and hirudin protects rat dorsal root ganglion neurons against high glucose-induced injury through Nrf-2/HO-1 activation and NF-κB inhibition.

To examine the effects of the combination of quercetin (Q), cinnamaldehyde (C) and hirudin (H), a Chinese medicine formula on high glucose (HG)-induced apoptosis of cultured dorsal root ganglion (DRG) neurons. DRG neurons exposed to HG (45 mmol/L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species (ROS) level and apoptosis were determined. The expression of nuclear factor of Kappa B (NF-κB), inhibitory kappa Bα(IκBα), phosphorylated IκBα and Nf-E2 related factor 2 (Nrf2) were examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay. The expression of hemeoxygenase-1 (HO-1), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and caspase-3 were also examined by RT-PCR and Western blot assay. HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway (P<0.05). Co-treatment with Q, C, H and their combination decreased HG-induced caspase-3 activation and apoptosis (P<0.05 or P<0.01). The expressions of NF-κB, IL-6 and TNF-α were down-regulated, and Nrf2/HO-1 expression was up-regulated (P<0.05 or P<0.01). QCH has better effect in scavenging ROS, activating Nrf-2/HO-1, and down-regulating the NF-κB pathway than other treatment group. DRG neurons' apoptosis was increased in diabetic conditions, which was reduced by QCH formula treatment. The possible reason could be activating Nrf-2/HO-1 pathway, scavenging ROS, and inhibition of NF-κB activation. The effect of QCH combination was better than each monomer or the combination of the two monomers.

Combination Therapy with Quercetin and 5-Fluorouracil Ameliorates 1,2-Dimethylhydrazine Induced Carcinogenesis in the Colon of Wistar Rats.

Background: Colorectal carcinoma (CRC) is a common cause of cancer-related death worldwide. 5-fluorouracil (5-FU), a first-line chemotherapeutic drug in CRC, has several side effects limiting its therapeutic outcomes. Quercetin (QU) is a dietary bioflavonoid with antioxidant and cytotoxic prooxidant properties. Here, we hypothesize that combination treatment with QU and 5-FU can modulate 1,2-dimethylhydrazine (DMH) induced histological and biochemical changes in the colon of Wistar rats. Methods: A Wistar rats CRC model was established and the animals were randomly divided into five groups. Rats in group A received a suspending vehicle. Group B rats received DMH twice a week subcutaneously for 4 weeks. Animals in the other groups (C, D and E) received the same treatment of DMH, along with QU or 5-FU (individually) or combined QU+5-FU treatment. Results: The DMH-treated rats developed adverse histological alterations (aberrant crypt foci, ACF) and biochemical changes (elevated serum CA19-9; reduced tissue levels of enzymatic antioxidants; elevated CDH12 protein expression and decreased SOX7 mRNA levels). Treatment of DMH-treated animals with QU+5-FU (but not with QU or 5-FU, individually) significantly reversed these changes (i.e., suppressed the formation of ACF; decreased the CA19-9 levels; reduced CDH12 protein expression and increased SOX7 mRNA expression). Conclusions: Conclusively, to the best of our knowledge, our study was the first to evaluate the effects of QU+5-FU treatment on the histological and molecular changes following DMH administration in a rat colon model. Our data suggest that combination therapy with QU+5-FU has therapeutic benefits in colon cancer induced by DMH, with potential for translation to spontaneous disease.

Combination of Quercetin and Green Tea Extract Increased Plasma Epicatechingallate and Decreased Urine Epigallocatechin and Epicatechin Concentrations

Preclinical studies have shown that the combination of quercetin (Q) and green tea (GT) extract enhanced the anti‐carcinogenic activity in a prostate cancer xenograft model, increased the bioavailability of GT polyphenols (P) and decreased P methylation compared to GT extract alone. In order to test the hypothesis in humans that Q in combination with GT extract would enhance bioavailability of GTP compared to GT extract consumption alone we enrolled 32 men diagnosed with prostate cancer and randomized them to receive 2 capsules of GT extract (240 mg) in combination with either 1 capsule of Q (400 mg) (GT+Q) or placebo (GT+PL) two times per day prior to prostatectomy. Blood and early morning spot urine were collected at baseline and at 3 weeks. Bioavailability of GTP and Q were tested at 3 weeks by sampling before and 2 hours after administration of GT and Q. Immediately after the surgery a small aliquot of prostate tissue was collected. All urine, blood and tissue samples were analyzed for GTP and Q by high performance liquid chromatography with coularray detection and mass‐spectrometry. Red blood cell (RBC) and prostate gene expression, protein expression and DNA and polyphenol methylation enzyme activity were determined. There was no liver toxicity in any subject. Q was increased 14‐fold, 12‐fold and 4.5‐fold in plasma, urine, and prostate tissue, respectively, in subjects given GT+Q by comparison to GT+PL. Plasma ECG was significantly increased in men consuming GT+Q compared to GT+PL consistent with an effect of Q on bioavailability of GT as previously observed in animals. Urinary excretion of EGC, 4'‐MeEGC and EC was significantly decreased in urine collected prior to surgery in participants consuming GT+Q compared to GT+PL. The percent of methylated EGC tended to increase from 36 to 79% in urine from men consuming GT+Q compared to GT+PL (p=0.137). ECG and/or EGCG were found in the prostate tissue of 31 out of 32 participants, but there was no difference in prostate GTP content between the GT+Q and GT+PL groups. There were also no epigenetic differences in prostate or RBC as determined by catechol‐methyltransferase and DNA‐methyltransferase gene and protein expression and enzyme activity. Further investigations are underway to determine whether the presence of quercetin in addition to GT polyphenols in the prostate modulated inflammation or oxidant stress in prostate tissue.Support or Funding InformationNIH RO3CA171583

The Effect of Combination of Quercetin And Glibenclamide on Myocardial Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Expression In Type 2 Diabetic Rat

Background. Diabetes mellitus (DM) is a metabolic disorder syndrome that marked by hyperglycemia. The main macrovascular complication is heart failure due to diabetic cardiomyopathy. Hyperglycemia can increase reactive oxygen species (ROS) and lipid peroxidation that induce cellular damage. Quercetin is an antioxidant that reduce hyperglycemia and ROS by modify the expression of nuclear factor erythroid 2-related factor 2 (Nrf 2).Objective. The aim of this research was to investigate the effect of combination of quercetin and glibenclamide on myocardial nuclear factor erythroid 2-related factor 2 (nrf 2) expression in type 2 diabetic rat compared with no combination.Methods. The rats were divided randomly into nine groups (each group consisted of four rats). The control group consist of a normal group that received placebo, DM control groups that received placebo and glibenclamide and intervention groups received quercetin 5, 20 and 80 mg/kgbw/day and combination of quercetin with 5 mg/kgbw/day of glibenclamide orally for a period of four weeks. The expression of myocardial Nrf 2 was measured by immunohistochemistry. Data was analyzed by ANOVA and p&lt;0.05 was considered as significant. Results. Twenty and 80 mg/kgbw/day of quercetin with or without combination with glibenclamide orally for a period of four weeks increase myocardial Nrf2 expression higher than placebo (p&lt;0.05). Eighty mg/kgbw/day of quercetin increase myocardial Nrf2 expression higher than 5 and 20 mg/kgbw/day (p&lt;0.05).Conclusion. From this study it can be suggested that there are significant different in expression level of myocardial Nrf2 of type 2 DM after a combination of quercetin and glibenclamide, quercetin alone, glibenclamide alone and placebo.Bangladesh Journal of Medical Science Vol.16(2) 2017 p.302-306

Complementary cereals and legumes for health: Synergistic interaction of sorghum flavones and cowpea flavonols against LPS-induced inflammation in colonic myofibroblasts.

Cereals and legumes are traditionally consumed together in many cultures, and may provide complementary health benefits beyond what is known about improved indispensable amino acid intake. Here, we use an in vitro model of inflammatory pathways to investigate whether the different flavonoids in sorghum and cowpea could synergistically reduce inflammation. Interactive effect of combining apigenin and quercetin, as well as extracts (70% acetone, v/v) from a flavone-dominated white sorghum and flavonol-dominated white cowpea, against LPS-induced NF-κB and downstream cytokines (TNF-α, IL-6, IL-8) gene and protein expression was evaluated using the CCD18Co colon myofibroblasts. Combination of apigenin and quercetin, and sorghum and cowpea extracts synergistically downregulated LPS-induced NF-κB gene and protein expression in a dose-dependent manner, with additive effect producing IC50 values that were 14.6 and 14.0 times, respectively, higher than 1:1 combined treatments. Similar strong synergistic interactions were observed for the downstream cytokines (IC50 values for additive effect 8.3-21 times higher than combined treatments). Furthermore, the ratios of the different combined treatments significantly affected the magnitude of synergy. Combining the structurally related cereal flavones and legume flavonols elicit strong synergistic anti-inflammatory response in LPS-stimulated nonmalignant colonocytes, likely by targeting interdependent mechanisms.

Antioxidant effect of quercetin in an extender containing DMA or glycerol on freezing capacity of goat semen

This study was performed to evaluate the effectiveness of quercetin as a non-enzymatic antioxidant in combination with glycerol or Dimethylacetamide (DMA), on freezability of goat semen. Ejaculates from four healthy mature Mahabadi goats were collected using an artificial vagina. After primary processing, semen was pooled and extended by egg yolk based extender supplemented with different concentrations of quercetin (10 or 20 μM) along with 5% glycerol or DMA. The extended semen was frozen and sperm motility parameters, viability, abnormality, membrane integrity and lipid peroxidation were assessed after thawing. Results showed that sperm viability, total motility, progressive motility, straightness (STR) and linearity (LIN) were higher (P < 0.05), and abnormality percentage and MDA concentration were lower (P < 0.05) in extender containing DMA. Similarly, higher (P < 0.05) total motility, progressive motility, viability and membrane integrity along with lower (P < 0.05) MDA level were noted in Q10 group. The lowest (P < 0.05) MDA level was observed in DMA extender containing moderate level of quercetin (Q10D). Also the STR was higher (P < 0.05) in Q10D compared to Q10G and Q20G groups. In conclusion, supplementation of extender with 10 μM quercetin in combination with DMA improves the goat sperm motion kinetics and suppresses lipid peroxidation after freezing and thawing. Furthermore, DMA is more effective cryoprotectant for the freezing of goat sperm.

Hyaluronic Acid Nanohydrogel Loaded With Quercetin Alone or in Combination to a Macrolide Derivative of Rapamycin RAD001 (Everolimus) as a New Treatment for Hormone-Responsive Human Breast Cancer.

The aim of this study is based on the evaluation of anticancer, anti-inflammatory activities, and cellular uptake of hyaluronic acid nanohydrogel of quercetin tested alone and in combination to a macrolide derivative of rapamycin RAD001 (everolimus) on hormone-responsive breast cancer cell line MCF-7. Biological investigations were focused on the receptor mediated cellular internalization of the nanohydrogel and its abilities to reduce secretion of several cytokines (IL-8, IL-6, IL-19), VEGF, and metalloproteases (MMP-2, MMP-9) under pro-inflammatory conditions. Nanohydrogel show a CD44 dependent endocytosis with evident time dependent cytoplasmatic accumulation with abilities to reduce secretion of all cytokines of ∼60% compared to untreated cells. Combination of formulated quercetin and everolimus leads to a synergistic cytotoxic effects with a Combination Index of 0.38. These results highlights the importance of synergistic effect of the hyaluronic acid nanohydrogel of quercetin with everolimus in the regulation of human breast cancer cell proliferation and emphasize the antitumor and anti-inflammatory properties of the nanocarrier. J. Cell. Physiol. 232: 2063-2074, 2017. © 2016 Wiley Periodicals, Inc.

Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats

The study aims to compare, through histological and biochemical studies, the effects of quercetin, melatonin and their combination in regulation of immuno-inflammatory mediators and heat shock protein expressions in sodium nitrite induced hypoxia in rat lungs. The results revealed that NaNO2 injection caused a significant decrease in Hb in rats, while serum levels of TNF-α, IL-6 and CRP, VEGF and HSP70 were elevated compared to the control group. Administration of melatonin, quercetin or their combination before NaNO2 injection markedly reduced these parameters. Histopathological examination of the lung tissue supported these biochemical findings. The study suggests that melatonin and/or quercetin are responsible for lung tissue protection in hypoxia by downregulation of immuno-inflammatory mediators and heat shock protein expressions. Pre-treatment of hypoxic animals with a combination of melatonin and quercetin was effective in modulating most of the studied parameters to near-normal levels.

Disruption of quercetin metabolism by fungicide affects energy production in honey bees (Apis mellifera)

Cytochrome P450 monooxygenases (P450) in the honey bee, Apis mellifera, detoxify phytochemicals in honey and pollen. The flavonol quercetin is found ubiquitously and abundantly in pollen and frequently at lower concentrations in honey. Worker jelly consumed during the first 3 d of larval development typically contains flavonols at very low levels, however. RNA-Seq analysis of gene expression in neonates reared for three days on diets with and without quercetin revealed that, in addition to up-regulating multiple detoxifying P450 genes, quercetin is a negative transcriptional regulator of mitochondrion-related nuclear genes and genes encoding subunits of complexes I, III, IV, and V in the oxidative phosphorylation pathway. Thus, a consequence of inefficient metabolism of this phytochemical may be compromised energy production. Several P450s metabolize quercetin in adult workers. Docking in silico of 121 pesticide contaminants of American hives into the active pocket of CYP9Q1, a broadly substrate-specific P450 with high quercetin-metabolizing activity, identified six triazole fungicides, all fungal P450 inhibitors, that dock in the catalytic site. In adults fed combinations of quercetin and the triazole myclobutanil, the expression of five of six mitochondrion-related nuclear genes was down-regulated. Midgut metabolism assays verified that adult bees consuming quercetin with myclobutanil metabolized less quercetin and produced less thoracic ATP, the energy source for flight muscles. Although fungicides lack acute toxicity, they may influence bee health by interfering with quercetin detoxification, thereby compromising mitochondrial regeneration and ATP production. Thus, agricultural use of triazole fungicides may put bees at risk of being unable to extract sufficient energy from their natural food.

The effect of quercetin and doxorubicin combination in inhibiting resistance in mcf-7 cell

Background: Doxorubicin chemotherapy may induce the development of resistance in the cancer cells. Overexpression of P-glycoprotein (P-gp) has prominent causative role in this process. Unfortunately, many inhibitory agents do not exert satisfying clinical outcome to overcome resistance. Quercetin, a polyphenolic compound, can be developed as P-gp inhibitor due to its cytotoxic properties.Objective: To investigate the effect of quercetin and doxorubicin combination in inhibiting the development of resistance in MCF-7 cell.Methods: Doxorubicin resistant MCF-7 cell were developed from the parent MCF-7 cell by exposing to 75 nM doxorubicin for 25 days. The inhibitory effect of resistance was evaluated via exposured to 75 nM doxorubicin and 750 nM quercetin combination in the same manner with resistance induction. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) citotoxicity assay and flowcytometry assay were performed to investigate the degree of resistance and to inhibit the development of resistance.Results: The exposure of 75 nM doxorubicin in MCF-7 cells (MCF-7 cells/dox75) exhibited sensitivity significantly decrease and upregulation of P-gp expression. The combination of 750 nM quercetin and 75 nM doxorubicin (MCF-7 cells/ dox75q750) caused a significantly increase in cell sensitivity to doxorubicin (p&lt;0,05) and a decrease in P-gp expression (p&gt; 0,05).Conclusions: The exposure of 75 nM doxorubicin led to the development of doxorubicin-acquired resistance MCF-7 cell. The combination of quercetin and doxorubicin have potency to inhibit the development of doxorubicin-acquired resistance MCF-7 cell by increasing cell sensitivity and reducing P-gp expression level.Bangladesh Journal of Medical Science Vol.16(1) 2017 p.91-97

Effects of Quercetin and Omega-3 Combination on Nuclear Factor Kappa B (NFκB) Expression Level in Pancreatic Tissue of Rats with Type-2 Diabetes Mellitus

Background: Hyperglycemia increases nuclear factor kappa B (NFκB) expression and promotes cellular injury. Quercetin and omega-3 are expected to regulate NFκB expression. This study aims to measure the effect of combination therapy with quercetin and omega-3 in lowering the expression of NFκB in the pancreatic tissue of rats with type-2 DM as compared to those treated with monotherapy with either agent. Methods: This experimental study involved the use of a paraffin block of pancreatic tissue from 24 male Wistar rats aged 3 months, weighing between 250 g and 350 g. All rats underwent induction of type-2 DM and were divided into 4 groups: K1 (treated daily with placebo), K2 (treated with quercetin at 20 mg·kgBW-1·d-1), K3 (treated with omega-3 at 100 mg·kgBW-1·d-1), and K4 (treated with quercetin at 20 mg·kgBW-1·d-1 and omega-3 at 100 mg·kgBW-1·d-1). Treatments were administered orally for four weeks. Once the treatment was completed, samples of pancreatic tissue were collected for the measurement of the percentage of NFκB expression using immunohistochemical (IHC) staining. Results:The average level of NFκB expression in the pancreatic nuclei of DM rats treated with the combination of omega-3 and quercetin was significantly lower than that of those treated with placebo, quercetin only, or omega-3 only (p &lt; 0.05). Conclusion: The combination of quercetin at 20 mg·kgBW-1·d-1 and omega-3 at 100 mg·kgBW-1·d-1 is significantly more effective in lowering the percentage of NFκB in pancreatic nuclei than monotherapy with either agent.

Neuroprotective potential of Quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity.

1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson's like symptoms in rodents. Quercetin (QC) is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability. Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants (e.g., Quercetin). Therefore, the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats. MPTP (100 μg/μL/rat, bilaterally) was injected intranigrally on days 1, 4 and 7 using a digital stereotaxic apparatus. QC (25 and 50 mg/kg, intragastrically) and QC (25 mg/kg, intragastrically) in combination with piperine (2.5 mg/kg, intragastrically) were administered daily for 14 days starting from day 8 after the 3rd injection of MPTP. On day 22, animals were sacrificed and the striatum was isolated for oxidative stress parameter (thiobarbituric acid reactive substances, nitrite and glutathione), neuroinflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α) and neurotransmitter (dopamine, norepinephrine, serotonin, gamma-aminobutyric acid, glutamate, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid) evaluations. Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance. Both QC (25 and 50 mg/kg) and QC (25 mg/kg) in combination with piperine (2.5 mg/kg), in particular the combination therapy, significantly improved MPTP-induced behavioral abnormalities in rats, reversed the abnormal alterations of neurotransmitters in the striatum, and alleviated oxidative stress and inflammatory response in the striatum. These findings indicate that piperine can enhance the antioxidant and anti-inflammatory properties of QC, and QC in combination with piperine exhibits strong neuroprotective effects against MPTP-induced neurotoxicity.

A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota.

Resveratrol and quercetin, widely found in foods and vegetables, are plant polyphenols reported to have a wide range of biological activities. Despite their limited bioavailabilities, both resveratrol and quercetin are known to exhibit anti-inflammation and anti-obesity effects. We hypothesized that gut microbiota may be a potential target for resveratrol and quercetin to prevent the development of obesity. The aim of this research was to confirm whether a combination of quercetin and resveratrol (CQR) could restore the gut microbiota dysbiosis induced by a high-fat diet (HFD). In this study, Wistar rats were divided into three groups: a normal diet (ND) group, a HFD group and a CQR group. The CQR group was treated with a HFD and administered with a combination of quercetin [30 mg per kg body weight (BW) per day] and resveratrol [15 mg per kg body weight (BW) per day] by oral gavage. At the end of 10 weeks, CQR reduced the body weight gain and visceral (epididymal, perirenal) adipose tissue weight. Moreover, CQR also reduced serum lipids, attenuated serum inflammatory markers [interleukin (IL)-6, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1] and reversed serum biochemical parameters (adiponectin, insulin, leptin, etc.). Importantly, our results demonstrated that CQR could modulate the gut microbiota composition. 16S rRNA gene sequencing revealed that CQR had an impact on gut microbiota, decreasing Firmicutes (P < 0.05) and the proportion of Firmicutes to Bacteroidetes (P = 0.052). CQR also significantly inhibited the relative abundance of Desulfovibrionaceae (P < 0.01), Acidaminococcaceae (P < 0.05), Coriobacteriaceae (P < 0.05), Bilophila (P < 0.05), Lachnospiraceae (P < 0.05) and its genus Lachnoclostridium (P < 0.001), which were reported to be potentially related to diet-induced obesity. Moreover, compared with the HFD group, the relative abundance of Bacteroidales_S24-7_group (P < 0.01), Christensenellaceae (P < 0.001), Akkermansia (P < 0.01), Ruminococcaceae (P < 0.01) and its genera Ruminococcaceae_UCG-014 (P < 0.01), and Ruminococcaceae_UCG-005 (P < 0.01), which were reported to have an effect of relieving HFD-induced obesity, was markedly increased in the CQR group. Overall, these results indicated that administration of CQR may have beneficial effects on ameliorating HFD-induced obesity and reducing HFD-induced gut microbiota dysbiosis.

Enhancement of Anti-inflammatory and Anti-allergic Activities with Combination of Luteolin and Quercetin in &lt;i&gt;in vitro&lt;/i&gt; Co-culture System

Enhancement of Anti-inflammatory and Anti-allergic Activities with Combination of Luteolin and Quercetin in &lt;i&gt;in vitro&lt;/i&gt; Co-culture System

Quercetin induces autophagy via FOXO1-dependent pathways and autophagy suppression enhances quercetin-induced apoptosis in PASMCs in hypoxia

Quercetin, an important dietary flavonoid has been demonstrated to potentially reverse or even prevent pulmonary arterial hypertension (PAH) progression. However, the effects of quercetin on apoptosis and autophagy in pulmonary arterial smooth muscle cells (PASMCs) have not yet been clearly elucidated. The current study found that quercetin significantly induce the apoptotic and autophagic capacities of PASMCs in vitro and in vivo in hypoxia. In addition, we found that quercetin increases FOXO1 (a major mediator in autophagy regulation) expression and transcriptional activity. Moreover, FOXO1 knockdown by siRNAs inhibited the phosphorylation of mTOR and 4E-BPI, which is downstream of P70-S6K, and markedly blocked quercetin-induced autophagy. We also observed that FOXO1-mediated autophagy was achieved via SESN3 not Rictor upregulation and after mTOR suppression. Furthermore, Treatment with autophagy-specific inhibitors could markedly enhance quercetin-induced apoptosis in PASMCs under hypoxia. Finally, quercetin in combination with autophagy inhibition treatment could enhance the therapeutic effects of quercetin in hypoxia-associated PAH in vivo. Taken together, quercetin could enhance hypoxia-induced autophagy through the FOXO1-SENS3-mTOR pathway in PASMCs. Combining quercetin and autophagy inhibitors may be a novel therapeutic strategy for treating hypoxia-associated PAH.