Administration Of Quercetin Research Articles

Quercetin, the Ingredient of Xihuang Pills, Inhibits Hepatocellular Carcinoma by Regulating Autophagy and Macrophage Polarization.

The key active component(s) in an anti-tumor preparation used in traditional Chinese medicine, Xihuang Pills, remains unclear. We used a network pharmacology analysis to construct a component-disease-target network diagram and used this to determine quercetin as a critical active ingredient in Xihuang Pills. Subsequently, human hepatocellular carcinoma (HCC) cell lines, H22 and HepG2 cells, were treated with quercetin, and BALB/c mice were injected with H22 cells and treated with different concentrations of quercetin. Tumor volume and weight were determined in these mice with and without quercetin administration. Immune and pro-inflammatory factors were measured using Enzyme Linked Immunosorbent Assay (ELISA). Macrophage polarization was assessed by western blot and flow cytometry. Finally, PD-L1, autophagy-related proteins, and the NF-κB pathway were also analyzed. Quercetin could significantly inhibit the proliferation, migration, and invasion characteristics of HCC cells and promote apoptosis in a concentration-dependent manner in vitro. After quercetin treatment, tumor volume and weight significantly decreased in vivo. Granulocyte-macrophage and granulocyte colony-stimulating factor (GM-CSF and G-CSF, respectively) levels were blunted in response to quercetin, as well as the PD-L1 level. CD86+ cell ratio was increased, while the CD206+ cell ratio was decreased, suggesting that macrophages tend to undergo M1 polarization in response to quercetin. The expression of LC3 II/I was increased, while the expression of p62 was down-regulated. The pro-inflammatory factors TNF-α, IL-6, and IL-17A, as well as NF-κB signaling were suppressed in a quercetin concentration-dependent manner. Quercetin is a key ingredient of anti-HCC activity in Xihuang Pills by regulating macrophage polarization and promoting autophagy via the NF-κB pathway.

Quercetin and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease, and results to opsomenorrhea or amenorrhea, hairy, acne, acanthosis, infertility, abortion. In the long term, PCOS may also increase the risk of endometrial cancer, diabetes, hypertension, dyslipidemia and other diseases. Till now there is no specific drug for PCOS due to the unclearness of the cause and pathogenesis, as current treatments for PCOS only target certain symptoms. Quercetin (QUR) is a flavonoid drug widely found in Chinese herbal medicines, fruits, leaves, vegetables, seeds and plants roots. Studies on other diseases have found that QUR has anti-oxidant, anti-inflammatory, anti-insulin resistance, anti-cancer and other effects. Some studies have shown that serum testosterone (T), luteinizing hormone (LH), the LH/follicule-stimulating hormone (FSH) ratio, fasting glucose, fasting insulin, HOMA-IR and lipid levels are reduced in PCOS patients with QUR treatment. However, the mechanisms of QUR in PCOS patients have not been completely elucidated. In this review, we retrospect the basic characteristics of QUR, and in vitro studies, animal experiments and clinical trials of QUR and plant extracts containing QUR in the treatment of PCOS. We also summarized the effects and mechanism of QUR in ovarian cells in vitro and PCOS model rats, the changes in relevant parameters after QUR administration in PCOS patients, and its potentially therapeutic applications.

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 Bioengineered Quercetin-Loaded 3D Bio-Polymeric Graft for Tissue Regeneration and Repair.

Phytochemicals extracted from plant sources have potential remedial effects to cure a broad range of acute to severe illnesses and ailments. Quercetin is a flavonoid isolated from different dietary sources such as vegetables and fruits, exhibiting strong anti-inflammatory, anti-oxidative and non-toxic effects on the biological system. However, the direct uptake or administration of quercetin results in loss of functionality, poor activity, and reduced shelf-life of the bioactive component. In this regard, to improve the uptake, potential, and efficiency of natural components with prolonged storage in the host's body after administration, numerous polymer drug delivery systems have been created. In the current study, three-dimensional (3D) porous (porosity: 92%; pore size: 81 µm) bio-polymeric foaming gelatin-alginate (GA) beads were fabricated for the entrapment of quercetin as therapeutic drug molecules-gelatin-alginate-quercetin (GAQ). The GAQ beads showed a significant uptake of quercetin molecules resulting in a reduction of reduced porosity up to 64% and pore size 63 µm with a controlled release profile in the PBS medium, showing ~80% release within 24 h. Subsequently, the GAQ beads showed remarkable antioxidant effects, and 95% anti-inflammatory activities along with remarkable in vitro cell culture growth and the observed proliferation of seeded fibroblast cells. Thus, we can conclude that the consistent release of quercetin showed non-toxic effects on normal cell lines and the bioactive surface of the GAQ beads enhances cell adhesion, proliferation, and differentiation more effectively than control GA polymeric beads and tissue culture plates (TCP). In summary, these findings show that these GAQ beads act as a biocompatible 3D construct with enormous potential in medicinal administration and tissue regeneration for accelerated healing.

Quercetin enhances survival and axonal regeneration of motoneurons after spinal root avulsion and reimplantation: experiments in a rat model of brachial plexus avulsion

BackgroundBrachial plexus avulsion (BPA) physically involves the detachment of spinal nerve roots themselves and the associated spinal cord segment, leading to permanent paralysis of motor function of the upper limb. Root avulsion induces severe pathological changes, including inflammatory reaction, oxidative damage, and finally massive motoneuron apoptosis. Quercetin (QCN), a polyphenolic flavonoid found in abundance in fruit and vegetables, has been reported to possess anti-oxidative, anti-inflammatory, and neuroprotective effects in many experimental models of both central nervous system (CNS) and peripheral nervous system (PNS) disorders. The purpose of this study was to investigate whether QCN could improve motor function recovery after C5–7 ventral root avulsion and C6 reimplantation in a rat model of BPA.MethodsThe right fifth cervical (C5) to C7 ventral roots were avulsed followed by re-implantation of only C6 to establish the spinal root avulsion plus re-implantation model in rats. After surgery, rats were treated with QCN (25, 50, and 100 mg/kg) by gavage for 2 or 8 consecutive weeks. The effects of QCN were assessed using behavior test (Terzis grooming test, TGT) and histological evaluation. The molecular mechanisms were determined by immunohistochemistry analysis and western blotting.ResultsOur results demonstrated that QCN significantly expedited motor function recovery in the forelimb as shown by the increased Terzis grooming test score, and accelerated motor axon regeneration as evidenced by the ascending number of Fluoro-Ruby-labeled and P75-positive regenerative motoneurons. The raised ChAT-immunopositive and cresyl violet-stained neurons indicated the enhanced survival of motoneurons by QCN administration. Furthermore, QCN treatment markedly alleviated muscle atrophy, restored functional motor endplates in biceps and inhibited the microglial and astroglia activation via modulating Nrf2/HO-1 and neurotrophin/Akt/MAPK signaling pathway.ConclusionsTaken together, these findings have for the first time unequivocally indicated that QCN has promising potential for further development into a novel therapeutic in conjunction with reimplantation surgery for the treatment of BPA.

Зміна окремих показників еритроцитів крові щурів за впливу гістаміну і кверцетину

Зміна окремих показників еритроцитів крові щурів за впливу гістаміну і кверцетину

Suppression of the Excitability of Rat Nociceptive Primary Sensory Neurons Following Local Administration of the Phytochemical, Quercetin

Although the modulatory effect of quercetin on voltage-gated Na, K, and Ca channels has been studied in vitro, the in vivo effect of quercetin on the excitability of nociceptive primary neurons remains to be determined. The aim of the present study was to examine whether acute local quercetin administration to rats attenuates the excitability of nociceptive trigeminal ganglion (TG) neurons in response to mechanical stimulation in vivo. Extracellular single unit recordings were made from TG neurons of anesthetized rats in response to orofacial non-noxious and noxious mechanical stimulation. The mean firing frequency of TG neurons in response to both non-noxious and noxious mechanical stimuli was dose-dependently inhibited by quercetin, and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. The inhibitory effect of quercetin lasted for 15 minutes and was reversible. The mean magnitude of inhibition on TG neuronal discharge frequency with 10 mM quercetin was almost equal to that of the local anesthetic, 2% lidocaine. These results suggest that local injection of quercetin into the peripheral receptive field suppresses the excitability of nociceptive primary sensory neurons in the TG, possibly via inhibition of voltage-gated Na channels and opening voltage-gated K channels. PerspectiveLocal administration of the phytochemical, quercetin, as a local anesthetic may provide relief from trigeminal nociceptive pain with smallest side effects, thus contributing to the area of complementary and alternative medicines.

The role of endothelial protection in the treatment of patients with arterial hypertension: the effectiveness of quercetin

The article presents the results of a clinical study of the effectiveness of the cytoprotective drug quercetin as a part of combined antihypertensive therapy on indices of endothelial function and daily blood pressure profile. The aim of the study. To conduct a comparative assessment of the dynamics of indices in 24-hour blood pressure monitoring (BPM) and cytokine levels in patients with hypertension, depending on using quercetin in treatment.Materials and methods. 120 patients with stage II hypertension of 2–3 degrees (66 female and 54 male) were examined. Patients were divided into 2 groups: Group I (study) – 58 patients who took quercetin (Corvitin®) in addition to basic therapy, mean age 57.87±13.6 years; II group (comparison) – 62 patients who underwent only basic antihypertensive therapy (Ramipril/Amlodipine), mean age 59.09±12.47 years. The results. During the administration of quercetin along with the standard basic therapy with the combination of Ramipril/Amlodipine in patients with stage II hypertension of 2-3 degrees of severity, more pronounced significant positive changes in the major indices of 24-hour BPM were observed, an increase in the ratio of people with a “dipper” profile due to a decrease in the number of patients with an insufficient reduction in nocturnal BP, an excessive drop in nocturnal BP or its persistent increase. The additional administration of quercetin contributes to the more effective correction of endothelial dysfunction indices: it significantly reduces the levels of soluble vascular cell adhesion molecules (s-VCAM), and soluble intercellular adhesion molecules 1 (s-ICAM-1), ET-1, IL-1, IL-6, TNF-a. During the administration of basic therapy, changes in IL-1 and ET-1 levels were less pronounced and insignificant. Correlation analysis shows the close relationship between a decrease in the main indices of 24-hour BPM and a decrease in the concentration of the cytokines, which characterize the state of endothelial dysfunction and systemic inflammation.Conclusion. The use of quercetin reliably reduces the levels of cytokines, which ensures a reduction in the manifestations of ED and contributes to better control of all blood pressure indices and normalization of the daily profile of blood pressure.

Quercetin Alleviates Lipopolysaccharide-Induced Cell Damage and Inflammation via Regulation of the TLR4/NF-κB Pathway in Bovine Intestinal Epithelial Cells.

Acute diarrhoea and intestinal inflammation represent one of the most prevalent clinical disorders of milk production, resulting in enormous annual financial damage for the dairy sector. In the context of an unsatisfactory therapeutic effect of antibiotics, the natural products of plants have been the focus of research. Quercetin is an important flavonoid found in a variety of plants, including fruits and vegetables, and has strong anti-inflammatory effects, so it has received extensive attention as a potential anti-inflammatory antioxidant. However, the underlying basis of quercetin on inflammatory reactions and oxidative tension generated by lipopolysaccharide (LPS) in bovine intestinal epithelial cells (BIECs) is currently unexplained. This research aimed to determine the influence of quercetin on LPS-induced inflammatory reactions, oxidative tension, and the barrier role of BIECs. Our findings demonstrated that BIEC viability was significantly improved in LPS-treated BIEC with 80 μg/mL quercetin compared with the control group. Indicators of oxidative overload and genes involved in barrier role revealed that 80 μg/mL quercetin efficiently rescued BIECs from oxidative and barrier impairment triggered by 5 μg/mL LPS. In addition, the mRNA expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, as well as chemokines CXCL2, CXCL5, CCL5, and CXCL8, was diminished in LPS-treated BIECs with 80 μg/mL quercetin compared with LPS alone. Furthermore, the mRNA expression of toll-like receptor 4 (TLR4), CD14, myeloid differential protein-2 (MD2), and myeloid differentiation primary response protein (MyD88) genes associated with the TLR4 signal mechanism was markedly reduced by the addition of quercetin to LPS-modulated BIECs, indicating that quercetin can suppress the TLR4 signal mechanism. We performed Western blotting on the NF-κB signalling mechanism and compared it with immunofluorescence to further corroborate this conclusion. The LPS treatment enhanced the proportions of p-IκBα/GAPDH and p-p65/GAPDH. Compared with the LPS-treated group, quercetin administration decreased the proportions of p-IκBα/GAPDH and p-p65/GAPDH. In addition, immunofluorescence demonstrated that quercetin greatly reduced the LPS-induced nuclear translocation of NF-κB p65 in BIECs. The benefits of quercetin on inflammatory reactions in LPS-induced BIECs may be a result of its capacity to inhibit the TLR4-mediated NF-κB signalling mechanism. These findings suggest that quercetin can be used as an anti-inflammatory reagent to treat intestinal inflammation induced by LPS release.

Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation

The role of NOD-like receptor protein 3 (NLRP3)-mediated macrophages pyroptosis in acute lung injury (ALI) is well-established. Quercetin (Que) is a natural bioflavonoid compound with anti-inflammatory and antioxidative properties that reportedly inhibits the NLRP3 inflammasome in sepsis-induced organ dysfunctions such as ALI. However, the mechanism underlying the inhibitory effect of quercetin on NLRP3 activation remains unclear. In this study, we established an endotoxin-induced ALI mouse model with an in vitro LPS challenge. We demonstrated that the administration of quercetin could significantly reduce pulmonary injury and decrease the production of pro-inflammatory cytokines. Moreover, we found that quercetin could inhibit the activation of the NLRP3 inflammasome by suppressing the nuclear accumulation of PKM2 and increasing SIRT1 levels. Importantly, treatment with SRT1720 (a specific SIRT1 activator) could inhibit the nuclear accumulation of PKM2 and the activation of NLRP3. Besides, preventing PKM2 dimerization with ML265 yielded an anti-inflammatory effect, similar to findings observed for SRT1720. In addition, we found that SIRT1 silencing or inhibition by EX527 could increase NLRP3 activation and nuclear accumulation of PKM2 and override quercetin-mediated anti-inflammatory activity. These findings indicated that quercetin could downregulate NLRP3 inflammasome activation by inhibiting the nuclear accumulation of PKM2 and upregulating SIRT1 expression, expanding the treatment landscape for ARDS.

What's New in Musculoskeletal Basic Science.

What's New in Musculoskeletal Basic Science.

A novel anti-atherosclerotic mechanism of quercetin: Competitive binding to KEAP1 via Arg483 to inhibit macrophage pyroptosis

Natural antioxidants represented by quercetin have been documented to be effective against atherosclerosis. However, the related mechanisms remain largely unclear. In this study, we identified a novel anti-atherosclerotic mechanism of quercetin inhibiting macrophage pyroptosis by activating NRF2 through binding to the Arg483 site of KEAP1 competitively. In ApoE−/− mice fed with high fat diet, quercetin administration attenuated atherosclerosis progression by reducing oxidative stress level and suppressing macrophage pyroptosis. At the cellular level, quercetin suppressed THP-1 macrophage pyroptosis induced by ox-LDL, demonstrated by inhibiting NLRP3 inflammasome activation and reducing ROS level, while these effects were reversed by the specific NRF2 inhibitor (ML385). Mechanistically, quercetin promoted NRF2 to dissociate from KEAP1, enhanced NRF2 nuclear translocation as well as transcription of downstream antioxidant protein. Molecular docking results suggested that quercetin could bind with KEAP1 at Arg415 and Arg483. In order to verify the binding sites, KEAP1 mutated at Arg415 and Arg483 to Ser (R415S and R483S) was transfected into THP-1 macrophages, and the anti-pyroptotic effect of quercetin was abrogated by Arg483 mutation, but not Arg415 mutation. Furthermore, after administration of adeno associated viral vector (AAV) with AAV-KEAP1-R483S, the anti-atherosclerotic effects of quercetin were almost abolished in ApoE−/− mice. These findings proved quercetins suppressed macrophage pyroptosis by targeting KEAP1/NRF2 interaction, and provided reliable data on the underlying mechanism of natural antioxidants to protect against atherosclerosis.

Amelioration of ethanol-induced gastric ulcer in rats by quercetin: implication of Nrf2/HO1 and HMGB1/TLR4/NF-κB pathways

Gastric ulcer is a serious medical condition that can be developed due to an imbalance in the protective and destructive factors of the gastric system. Available therapies do not provide definite cure, thus, there is an urge to seek for alternative treatments. Quercetin is a natural flavonoid that possesses antioxidant and anti-inflammatory properties. In the current study, the antiulcerogenic effect of quercetin in ethanol-induced gastric ulcer (EI-GU) rat model was compared to Antodine® (a reference drug), to elucidate the potential underlying mechanisms. Quercetin (50 mg/kg) and Antodine® (20 mg/kg) were given orally for one week post ulcer induction by ethanol. EI-GU was associated with downregulation of SOD, CAT, Nrf2 and HO1, and accompanied by upregulation of inflammatory markers (i.e., HMGB1, NF-κB and TNFα) and an increase in Bax/Bcl2 ratio. Administration of quercetin resulted in a significant reduction in gastric volume in the stomach of ulcerative rats by 86% and a significant decrease in gastric lesion count by 3.5- folds, as compared with the ulcerative rats. Moreover, rats treated with quercetin showed upregulation of Nrf2 by 3.3-fold change and in HO1 by 3.5-fold change when compared to ulcerated rats, and decreased HMGB1, TLR4, NF-κB p65 and TNF-α by 50%, 53%, 52.9% and 54.9%, respectively. Treatment of rats with quercetin reduced Bax and Bax/Bcl2 ratio and increased Bcl2 relative to ulcerated rats. Thus, it can be concluded that the ulcerogenic curative properties of quercetin were mediated by antioxidant, anti-inflammatory and antiapoptotic activities.

Reversal of oxidative stress, cytokine toxicity and DNA fragmentation by quercetin in dizocilpine-induced animal model of Schizophrenia.

Quercetin, a polyphenolic compound found in a variety of plant products possesses various biological activities and beneficial effects on human health. Schizophrenia (SZ) is one of the neuropsychiatric disorders in human beings with rapid mortality and intense morbidity which can be treated with antipsychotics, but these commercial drugs exert adverse effects and have less efficacy to treat the full spectrum of SZ. The present study was conducted to evaluate neuroprotective effects of quercetin in the preventive and therapeutic treatment of SZ. Quercetin was administered as pre- and post-regimens at the dose of 50mg/kg in dizocilpine-induced SZ rat model for two weeks. Rats were then subjected for the assessment of different behaviors followed by biochemical, neurochemical, and inflammatory marker analyses. The present findings revealed that quercetin significantly reverses the effects of dizocilpine-induced psychosis-like symptoms in all behavioral assessments as well as it also combats oxidative stress. This flavonoid also regulates dopaminergic, serotonergic, and glutamatergic neurotransmission. A profound effect on inflammatory cytokines and decreased %DNA fragmentation was also observed following the administration of quercetin. The findings suggest that quercetin can be considered as a preventive as well as therapeutic strategy to attenuate oxidative stress and cytokine toxicity, regulate neurotransmission, and prevent enhanced DNA fragmentation that can lead to the amelioration of psychosis-like symptoms in SZ.

Poly(1-vinylpyrrolidone-co-vinyl-acetate)-based electrospun dissolvable nanofibrous film for quercetin administration

This study used electrospinning to produce a water-soluble polymeric nanofibrous film incorporated with quercetin. Scanning Electron Microscopy showed that the diameter of the nanofibers decreased from (670 ± 200) nm to (390 ± 90) nm as the amount of quercetin increased from 0% to 15%. The FTIR confirmed the presence of quercetin in the films and suggested the formation of physical interactions between the drug and the polymer. The XRD results confirmed the amorphous character of the nanofibers, and the loss of crystallinity by quercetin, due to the electrospinning process itself and the physical interactions with the polymer. The dissolution assays confirmed that the nanofibers and quercetin completely dissolved in the medium. This dissolution process reached equilibrium within 3 min. Although the material would not be effective as a controlled drug delivery device, it would be effective as a dissolvable film. The quick dissolution of both the drug and the matrix is attractive for the administration of quercetin because it would increase the bioavailability of the drug in the body, overcoming the limited dissolution of crystalline quercetin.

Evidence for Quercetin as a Dietary Supplement for the Treatment of Cardio-Metabolic Diseases in Pregnancy: A Review in Rodent Models.

Quercetin supplementation during pregnancy and lactation has been linked to a lower risk of maternal cardio-metabolic disorders such as gestational diabetes mellitus (GDM), dyslipidemia, preeclampsia, attenuation of malnutrition-related conditions, and gestational obesity in animal studies. Pre-clinical studies have shown that maternal supplementation with quercetin reduces cardio-metabolic diseases in dams and rodents’ offspring, emphasizing its role in modifying phenotypic plasticity. In this sense, it could be inferred that quercetin administration during pregnancy and lactation is a viable strategy for changing cardio-metabolic parameters throughout life. Epigenetic mechanisms affecting the AMP-activated protein kinase (AMPK), nuclear factor-kappa B (NF-κB), and phosphoinositide 3-kinase (PI3 K) pathways could be associated with these changes. To highlight these discoveries, this review outlines the understanding from animal studies investigations about quercetin supplementation and its capacity to prevent or decrease maternal and offspring cardio-metabolic illnesses and associated comorbidities.

Possible mechanisms involved in the testicular-protective property of quercetin in rats exposed to endosulfan toxicity

The study investigated the effects of quercetin and putative mechanisms involved against endosulfan-testicular impairments in rats. Rats were allotted into five treatment groups (n = 5). Groups 1–2 had normal saline and maize oil (vehicle) (10 mL/kg), group 3 received quercetin (20 mg/kg), 4–5 had endosulfan (5 mg/kg, p.o) orally for 28 days. However, from days 14–28, group 4 received an additional dose of vehicle (10 mL/kg, p.o./day), while group 5 received quercetin (20 mg/kg, p.o./day). Thereafter, blood samples and testes were harvested for markers of cholinergic, hormonal and testicular oxido-nitrergic, inflammatory, apoptosis and proton pump ATPase activities. Also, testicular histopathological changes were also evaluated alongside with germ cell count, testicular injury and spermatogenesis score. Quercetin increased testicular/body weights and spermatogenesis, androgenic hormones (follicle stimulating hormones, FSH; luteinizing hormone, LH; testosterone), acetylcholinesterase levels and attenuated altered membrane integrity, DNA fragmentation, increased caspases-3 levels in rats exposed to endosulfan. Moreover, quercetin increased testicular B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x-protein (Bax) and proton pump adenosine trisphosphate (ATPase) and sialic acid levels. Of note, quercetin reversed endosulfan-mediated increased malondialdehyde, nitrite, peroxynitrite formation, 8-hydroxy-2′-deoxyguanosine and lowered antioxidant enzymes in the testes. The increased levels of testicular myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) by endosulfan were also reduced by quercetin administration. Additionally, quercetin attenuate endosulfan-induced testicular histopathological changes of rats. Our findings showed that quercetin significantly inhibited endosulfan-induced testicular damage and altered spermatogenesis through inhibition of oxido-nitrergic pathway, inflammatory mediators, apoptosis, acetylcholinesterase activity and enhancement of testicular hormones and improvement in testicular ATPase activity.

Effects of dietary quercetin on growth, antioxidant capacity, immune response and immune-related gene expression in snakehead fish, Channa argus

The present study aimed to evaluate the effects of quercetin-supplemented in diet on growth, antioxidant capacity and immune response and immune-related gene expression of Channa argus (C. argus) (initial weight, 24.50 ± 0.24 g). A basal diet was supplemented with quercetin at 0, 150, 300 or 450 mg kg−1 and feed to C. argus 56 days. Weight gain (WG) and specific growth rate (SGR) were significantly increased (P < .05), and feed conversion ratio (FCR) were significantly decreased (P < .05) with the increase of dietary quercetin levels from 0 to 450 mg kg−1. Supplemented quercetin (150, 300 or 450 mg kg−1) significantly enhanced (P < .05) serum or tissues superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), lysozyme (LZM) activity and complement 3 (C3), complement 4 (C4), immunoglobulin M (IgM) concentration. Meanwhile, quercetin administration significantly up-regulated (P < .05) the expression of immune-related cytokines (interleukin-1β[IL-1β], tumor necrosis factor-α[TNF-α], interleukin-8[IL-8], interleukin-10[IL-10]) in liver, spleen, kidney and intestine of C. argus. These results indicated that dietary supplement quercetin could enhance growth, antioxidant capacity, immune response and regulated immune-related genes expression of C. argus, with greatest effects in C. argus given 300 mg kg−1 quercetin for 56 days.

Modulatory effects of concomitant quercetin/sitagliptin administration on the ovarian histological and biochemical alterations provoked by doxorubicin in a streptozotocin-induced diabetic rat model

ABSTRACT Limited literature was available on the effects of sitagliptin or quercetin treatments on doxorubicin induced ovarian dysfunction in diabetic animals. The study aim was test the efficacy and suggested mechanisms of quercetin/sitagliptin combined treatment on the doxorubicin-induced ovarian toxicity in rat model with streptozotocin-induced diabetes. Forty eight female Wistar rats were divided into six groups: 1) Control; 2) Streptozotocin induced diabetes; 3) Streptozotocin-induced diabetes + doxorubicin ovarian damage; 4) Streptozotocin-induced diabetes + doxorubicin ovarian damage with; 5) Streptozotocin-induced diabetes + doxorubicin ovarian damage with sitagliptin treatment and 6) Streptozotocin-induced diabetes + doxorubicin ovarian damage with concomitant quercetin/sitagliptin treatment. Biochemical tests for serum estrogen, progesterone, insulin, blood glucose, and ovarian levels of malondialdehyde, nitric oxide, and superoxide dismutase and qRT-PCR for NOBOX, FSHr, and iNOS genes were performed. Histological evaluation was done on ovary sections with hematoxylin and eosin and immunohistochemistry for 8-OHdG and iNOS followed by morphometric analysis. The streptozotocin-induced diabetic group showed varying degrees of follicle atresia and altered biochemical parameters, both were marked in the streptozotocin-induced diabetic + doxorubicin group. The mRNA of NOBOX, FSHr, and iNOS genes were disturbed with increased immunoexpression of iNOS and 8-OHdG. Quercetin and/or sitagliptin administration improved all altered histological and biochemical parameters and was more effective as a combined treatment. The study suggested equal efficacy of both quercetin and sitagliptin in mitigating the doxorubicin-induced ovarian toxicity in the streptozotocin diabetic rat model, and the combined therapy showed anti-inflammatory, anti-antioxidant, and anti-DNA damage mechanisms.

Evaluation of protective effects of quercetin against cypermethrin-induced lung toxicity in rats via oxidative stress, inflammation, apoptosis, autophagy, and endoplasmic reticulum stress pathway.

Cypermethrin (CYP), a type II synthetic pyrethroid, is the most widely used insecticide worldwide. Inhalation of it may cause side effects. This study is aimed to examine potential protection of quercetin (QUE) which is a well-known antioxidant in CYP-induced lung toxicity. Accordingly, 35 Spraque Dawley male rats were divided into five equal groups as follows: I-Control group, II-QUE group (50 mg/kg/b.w. QUE), III-CYP group (25 mg/kg/b.w. CYP), IV-CYP + QUE 25 (25 mg/kg/b.w. CYP + 25 mg/kg/b.w. QUE), V-CYP + QUE (25 mg/kg/b.w. CYP + 50 mg/kg/b.w. QUE) were treated with oral gavage throughout 28 days. CYP intoxication was associated with increased malondialdehyde level while glutathione concentration, activities of glutathione peroxidase, superoxide dismutase, and catalase reduced. CYP adminisitration caused of apoptosis in the lung by up-regulating caspase-3 and Bax levels and down-regulating Bcl-2. CYP also caused of endoplasmic reticulum (ER) stress by increasing mRNA transcript levels of PERK, IRE1, ATF6, and GRP78. Additionally, it was observed that CYP administration activated IL-6/JAK2/STAT3/MAPK14 signaling pathway and levels of IL-1β, NF-κB, TNF-α, and iNOS in the lung tissue. Therefore, it was determined that CYP administration triggered autophagy by upregulating LC3A and LC3B mRNA transcript levels. Moreover, the protein levels of NF-κB, caspase-3, Bax, Bcl-2, and cytochorme-c were examined by Western blot analysis. However, co-treatment with QUE at a dose of 25 and 50 mg/kg considerably protective oxidative stress, inflammation, apoptosis, ER stress, autophagy, and IL-6/JAK2/STAT3/MAPK14 signaling pathway in lung tissue. Overall, the findings of this study suggest that lung damage associated with CYP toxicity could be protected by QUE administration.