RESUMO
This study aimed to evaluate the anti-inflammatory and analgesic properties of the methanolic extract of Opuntia ficus indica L. in small animal (rats and mice model). The current treatment for febrile conditions often involves the use of non-steroidal anti-inflammatory drugs (NSAIDs), which can have adverse effects, particularly gastrointestinal ulcers. Therefore, there is a growing need to explore natural alternatives with fewer side effects. The study utilized various experimental models to assess the effects of the extract. The results demonstrated a significant analgesic effect of the extract, as evidenced by a reduction in pain induced by acetic acid and hot plate tests. Additionally, the extract exhibited anti-inflammatory effects, as indicated by a decrease in carrageenan-induced paw edema and dextran-induced inflammation. To gain insights into the chemical composition of the extract, HPLC analysis was conducted. The analysis successfully identified and quantified 20 compounds, including luteolin, galangin, catechin, thymol, methylated quercetin, quercetin, rutin, acacetin, hesperidin, apigenin, kaempferol, pinocembrin, chrysin, gallic acid, caffeic acid, ascorbic acid, ferulic acid, m-coumaric acid, rosmarinic acid, and trans-cinnamic acid.The findings suggest that Opuntia ficus indica L. extract holds promise as an effective and reasonably priced natural remedy for pain and inflammation in rats and mice model. The comprehensive chemical composition analysis provided valuable insights into the presence of various bioactive compounds, which may contribute to the observed therapeutic effects. Further research and exploration of the extract's mechanisms of action are warranted to fully understand its potential in small animal healthcare.
Assuntos
Opuntia , Camundongos , Ratos , Animais , Opuntia/química , Quercetina/efeitos adversos , Quercetina/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Analgésicos/efeitos adversos , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Dor/induzido quimicamenteRESUMO
The current study aims to quantify HPLC-DAD polyphenolics in the crude extracts of Desmodium elegans, evaluating its cholinesterase inhibitory, antioxidant, molecular docking and protective effects against scopolamine-induced amnesia in mice. A total of 16 compounds were identified which include gallic acid (239 mg g-1), p-hydroxybenzoic acid (11.2 mg g-1), coumaric acid (10.0 mg g-1), chlorogenic acid (10.88 mg g-1), caffeic acid (13.9 mg g-1), p-coumaroylhexose (41.2 mg g-1), 3-O-caffeoylquinic acid (22.4 mg g-1), 4-O-caffeoylquinic acid (6.16 mg g-1), (+)-catechin (71.34 mg g-1), (-)-catechin (211.79 mg g-1), quercetin-3-O-glucuronide (17.9 mg g-1), kaempferol-7-O-glucuronide (13.2 mg g-1), kaempferol-7-O-rutinoside (53.67 mg g-1), quercetin-3-rutinoside (12.4 mg g-1), isorhamnetin-7-O-glucuronide (17.6 mg g-1) and isorhamnetin-3-O-rutinoside (15.0 mg g-1). In a DPPH free radical scavenging assay, the chloroform fraction showed the highest antioxidant activity, with an IC50 value of 31.43 µg mL-1. In an AChE inhibitory assay, the methanolic and chloroform fractions showed high inhibitory activities causing 89% and 86.5% inhibitions with IC50 values of 62.34 and 47.32 µg mL-1 respectively. In a BChE inhibition assay, the chloroform fraction exhibited 84.36% inhibition with IC50 values of 45.98 µg mL-1. Furthermore, molecular docking studies revealed that quercetin-3-rutinoside and quercetin-3-O-glucuronide fit perfectly in the active sites of AChE and BChE respectively. Overall, the polyphenols identified exhibited good efficacy, which is likely as a result of the compounds' electron-donating hydroxyl groups (-OH) and electron cloud density. The administration of methanolic extract improved cognitive performance and demonstrated anxiolytic behavior among tested animals.
Assuntos
Doença de Alzheimer , Escopolamina , Camundongos , Animais , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Polifenóis/efeitos adversos , Clorofórmio/efeitos adversos , Quercetina/efeitos adversos , Simulação de Acoplamento Molecular , Glucuronídeos , Extratos Vegetais/efeitos adversos , Inibidores da Colinesterase/efeitos adversos , Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Antioxidantes/efeitos adversos , Metanol/química , Modelos Animais , RutinaRESUMO
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-dependent side effects of cisplatin. The loss of sensory neurons is observed in CIPN. There are many methods to minimalize CIPN symptoms such as pharmacological agents and photobiostimulation but the mechanisms of these methods are unclear. Our study is aimed at determining the effects of quercetin and low-level laser therapy (LLLT) in undifferentiated and nerve growth factor-differentiated PC12 cells in cisplatin-induced peripheral neuropathy. PC12 cells with cisplatin were co-treated with quercetin and LLLT (diode pumped all-solid-state laser, 670 nm, output 500 mW, and the laser beam surface area was 1.96 cm2). The effects of quercetin and LLLT on GAP-43 and Synapsin I expressions were analyzed by real-time PCR, cell viability was assessed by MTT assay, Annexin and dead assay measured the induction of apoptosis, the alterations in mitopotential were assessed by mitopotential assay, and lactate dehydrogenase activity in cells was analyzed. All experiment data were analyzed by the Tukey test and applied as a post hoc test, and statistical evaluation was made. Our results indicated that cisplatin increased apoptosis (24,210 ± 2189, 46,504 ± 8246) cells, mitochondrial dysfunction (44,312 ± 0.751, 68,788 ± 1271), and LDH activity (62,821 ± 8245, 87,838 ± 8116). Furthermore, it decreased cell viability (42,447 ± 1780, 36,140 ± 3682) and inhibited GAP-43 and Synapsin I genes in undifferentiated and differentiated PC12 cells. However, apoptosis, the alterations in mitopotential, and lactate dehydrogenase activity decreased by applications of quercetin and LLLT. It has been recommended that quercetin and low-level laser therapy roles on cisplatin-induced peripheral neuropathy should be investigated in vivo, and the relationship between quercetin and low-level laser therapy should be molecular.
Assuntos
Antineoplásicos , Terapia com Luz de Baixa Intensidade , Doenças do Sistema Nervoso Periférico , Ratos , Animais , Cisplatino/efeitos adversos , Quercetina/efeitos adversos , Terapia com Luz de Baixa Intensidade/métodos , Proteína GAP-43 , Sinapsinas , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Lactato Desidrogenases , Antineoplásicos/farmacologiaRESUMO
Abstract Suanzaoren Decoction (SZRD) is an ancient prescription used in the treatment of insomnia. This study aimed to investigate the components and targets of SZRD in treating insomnia. First, the compounds of five herbs in SZRD were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the putative targets for treating insomnia were obtained from DrugBank to construct the herb-compound-target- disease network. A protein-protein interaction (PPI) network was constructed in the STRING database, and then Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the mechanism of action of intersection target. Finally, 30 mice were divided into five groups: control, model, and quercetin groups (100, 50, 25 mg/kg). The sleep latency and duration of pentobarbital-induced sleeping were measured. The production of interleukin-6 (IL-6) and γ-aminobutyric acid (γ-GABA) was detected by using an enzyme-linked immunosorbent assay kit (ELISA), and Gamma-aminobutyric acid type a receptor subunit alpha1 (GABRA1) was tested by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). A total of 152 active ingredients, including 80 putative targets of SZRD, were obtained. The main active compounds included quercetin and kaempferol, and the key targets involved IL-6 and nitric oxide synthase 3 (NOS3). The results of pathway enrichment analysis indicated that the putative targets of SZRD mainly participated in Neuroactive ligand-receptor interaction. The experiment of P-chlorophenylalanine (PCPA)-induced insomnia model showed that quercetin obviously shortened the sleep latency and prolonged the sleep duration of the insomnia model. The production of IL-6, γ-GABA, and GABRA1 mRNA was significantly increased in mice treated with quercetin. This study predicted the active ingredients and potential targets of SZRD on insomnia on the basis of a systematic network pharmacology approach and illustrated that SZRD might exert hypnotic effects via regulating IL-6, γ-GABA, and GABRA1
Assuntos
Animais , Masculino , Feminino , Ratos , Extratos Vegetais/farmacologia , Distúrbios do Início e da Manutenção do Sono/classificação , Pentobarbital/análise , Quercetina/efeitos adversos , Quempferóis/efeitos adversosRESUMO
Quercetin is a flavonoid that is widely found in fruits and vegetables. Quercetin inhibits cyclooxygenase-2 and modulates voltage-gated ion channels, however, its effect on nociceptive neuron-associated inflammatory hyperalgesia remains unknown. The present study investigated under in vivo conditions whether systemic administration of quercetin attenuates the inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) neurons associated with mechanical hyperalgesia and compared its effect to the non-steroidal anti-inflammatory drug, diclofenac. Complete Freund's adjuvant was injected into the whisker pads of rats to induce inflammation, and then mechanical stimulation was applied to the orofacial area to assess the threshold of escape. The mechanical threshold was significantly lower in inflamed rats compared to uninjected naïve rats, and this lowered threshold returned to control levels 2 days after administration of quercetin or diclofenac. The mean discharge frequency of SpVc wide-dynamic range (WDR) neurons to both non-noxious and noxious mechanical stimuli in inflamed rats was significantly decreased after quercetin or diclofenac administration under combination of three anesthetic agents (medetomidine, midazolam and butorphanol). In addition, the increased mean spontaneous discharge of SpVc WDR neurons in inflamed rats significantly decreased after quercetin or diclofenac administration. Similarly, quercetin or diclofenac restored the expanded mean receptive field size in inflamed rats to control levels. In this study, the combination of three anesthetic agents did not result in any obvious "noxious pinch-evoked after discharges" in CFA inflamed day 2 rat as described previously in pentobarbital-anesthetized rats. Together, these results suggest that administration of quercetin attenuates inflammatory hyperalgesia associated with hyperexcitability of nociceptive SpVc WDR neurons via inhibition of the peripheral cyclooxygenase-2 signaling cascade and voltage-gated ion channels. These findings support the proposed potential of quercetin as a therapeutic agent in complementary alternative medicine strategies for preventing trigeminal inflammatory mechanical hyperalgesia.
Assuntos
Hiperalgesia , Nociceptores , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Ciclo-Oxigenase 2 , Diclofenaco/efeitos adversos , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/complicações , Inflamação/tratamento farmacológico , Canais Iônicos , Compostos Fitoquímicos/efeitos adversos , Quercetina/efeitos adversos , Ratos , Ratos WistarRESUMO
OBJECTIVE: To analyse the antinociceptive interaction between quercetin (QUER) and diclofenac (DIC) in experimental arthritic gout-pain. METHODS: The antinociceptive effect of DIC and QUER alone and in combination were evaluated using an arthritic gout-pain model. Pain was induced through intra-articular administration of uric acid in the rats and the treatments were administered 2 h later. Additionally, the cyclooxygenase (COX) activity was determined in rats treated with DIC, QUER and their combination. KEY FINDINGS: DIC induced a maximal effect of 69.7 ± 2.7% with 3.1 mg/kg; whereas QUER only produced 17.6 ± 2.6% with the maximal dose (316 mg/kg). Ten of twelve DIC + QUER combinations showed a lesser antinociceptive effect than DIC alone did (P < 0.05). Moreover, DIC reduced total-COX (70.4 ± 1.3 versus 52.4 ± 1.8 and 77.4 ± 9.0 versus 56.1 ± 1.3, P < 0.05) and COX-2 (60.1 ± 1.0 versus 42.4 ± 1.8 and 58.1 ± 2.4 versus 48.7 ± 1.3, P < 0.05) activity after 1 and 3 h, respectively. Nevertheless, only the COX-2 activity induced by DIC was prevented in the presence of QUER (63.2 ± 3.0 versus 60.1 ± 1.0 and 56.6 ± 1.3 versus 58.1 ± 2.4 at 1 and 3 h, respectively). CONCLUSIONS: All these data demonstrated that the simultaneous administration of QUER + DIC produces an unfavorable interaction on the antinociceptive effect of DIC. Therefore, this combination might not be recommendable to relieve arthritic gout-pain.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Artralgia/tratamento farmacológico , Diclofenaco/administração & dosagem , Gota/tratamento farmacológico , Interações Ervas-Drogas , Nociceptividade/efeitos dos fármacos , Quercetina/administração & dosagem , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Artralgia/metabolismo , Artrite/tratamento farmacológico , Artrite/metabolismo , Artrite/patologia , Diclofenaco/efeitos adversos , Diclofenaco/uso terapêutico , Modelos Animais de Doenças , Quimioterapia Combinada , Gota/metabolismo , Gota/patologia , Articulações/efeitos dos fármacos , Magnoliopsida/química , Masculino , Manejo da Dor , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Extratos Vegetais/uso terapêutico , Prostaglandina-Endoperóxido Sintases/metabolismo , Quercetina/efeitos adversos , Quercetina/uso terapêutico , Ratos Wistar , Ácido ÚricoRESUMO
BACKGROUND: The ingestion of flavonoids has been reported to be associated with reduced cardiovascular disease risk. Quercitrin is a common flavonoid in nature, and it exhibits antioxidant properties. Although the process of thrombogenesis is intimately related to cardiovascular disease risk, it is unclear whether quercitrin plays a role in thrombogenesis. PURPOSE: The aim of this study was to examine the antiplatelet effect of quercitrin in platelet activation. METHODS: Platelet aggregation, granule secretion, calcium mobilization, and integrin activation were used to assess the antiplatelet activity of quercitrin. Antithrombotic effect was determined in mouse using ferric chloride (FeCl3)-induced arterial thrombus formation in vivo and thrombus formation on collagen-coated surfaces under arteriolar shear in vitro. Transection tail bleeding time was used to evaluate whether quercitrin inhibited primary hemostasis. RESULTS: Quercitrin significantly impaired collagen-related peptide-induced platelet aggregation, granule secretion, reactive oxygen species generation, and intracellular calcium mobilization. Outside-in signaling of αIIbß3 integrin was significantly inhibited by quercitrin in a concentration-dependent manner. The inhibitory effect of quercitrin resulted from inhibition of the glycoprotein VI-mediated platelet signal transduction during cell activation. Further, the antioxidant effect is derived from decreased phosphorylation of components of the TNF receptor-associated factor 4/p47phox/Hic5 axis signalosome. Oral administration of quercitrin efficiently blocked FeCl3-induced arterial thrombus formation in vivo and thrombus formation on collagen-coated surfaces under arteriolar shear in vitro, without prolonging bleeding time. Studies using a mouse model of ischemia/reperfusion-induced stroke indicated that treatment with quercitrin reduced the infarct volume in stroke. CONCLUSIONS: Our results demonstrated that quercitrin could be an effective therapeutic agent for the treatment of thrombotic diseases.
Assuntos
Fibrinolíticos/farmacologia , Hemostasia/efeitos dos fármacos , Quercetina/análogos & derivados , Trombose/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Animais , Artérias , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Quercetina/efeitos adversos , Quercetina/farmacologia , Traumatismo por Reperfusão/induzido quimicamente , Trombose/induzido quimicamente , Trombose/metabolismoRESUMO
INTRODUCTION: Quercetin is a plant flavonoid and has potent antioxidant and anti-inflammatory properties. In a preclinical model of chronic obstructive pulmonary disease (COPD), quercetin reduced markers of both oxidative stress and lung inflammation and also reduced rhinovirus-induced progression of lung disease. Although quercetin appears to be an attractive natural alternative to manage COPD, the safety of quercetin supplementation in this population is unknown. METHODS: We recruited COPD patients with mild-to-severe lung disease with FVE1 ranging between >35% and <80% and supplemented with either placebo or quercetin at 500, 1000 or 2000 mg/day in a dose-escalation manner. The duration of quercetin supplementation was 1 week. RESULTS: Patients had no study drug-related severe adverse events based on blood tests, which included both complete blood counts and evaluation of comprehensive metabolic panel. One of the patients reported mild adverse events included gastro-oesophageal reflux disease, which was observed in both placebo and quercetin groups. CONCLUSIONS: Quercetin was safely tolerated up to 2000 mg/day as assessed by lung function, blood profile and COPD assessment test questionnaire. TRIAL REGISTRATION NUMBER: NCT01708278.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quercetina/administração & dosagem , Idoso , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Glicemia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Quercetina/efeitos adversos , Testes de Função Respiratória , Índice de Gravidade de DoençaRESUMO
SCOPE: Hepatic LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) regulate the clearance of plasma LDL-cholesterol (LDL-C): LDLR promotes it, and PCSK9 opposes it. These proteins also express in pancreatic ß cells. Using cultured hepatocytes, we previously showed that the plant flavonoid quercetin-3-glucoside (Q3G) inhibits PCSK9 secretion, stimulated LDLR expression, and enhanced LDL-C uptake. Here, we examine whether Q3G supplementation could reverse the hyperlipidemia and hyperinsulinemia of mice fed a high-cholesterol diet, and how it affects hepatic and pancreatic LDLR and PCSK9 expression. METHODS AND RESULTS: For 12 weeks, mice are fed a low- (0%) or high- (1%) cholesterol diet (LCD or HCD), supplemented or not with Q3G at 0.05 or 0.1% (w/w). Tissue LDLR and PCSK9 is analyzed by immunoblotting, plasma PCSK9 and insulin by ELISA, and plasma cholesterol and glucose by colorimetry. In LCD-fed mice, Q3G has no effect. In HCD-fed mice, it attenuates the increase in plasma cholesterol and insulin, accentuates the decrease in plasma PCSK9, and increases hepatic and pancreatic LDLR and PCSK9. In cultured pancreatic ß cells, however, it stimulates PCSK9 secretion. CONCLUSION: In mice, dietary Q3G could counter HCD-induced hyperlipidemia and hyperinsulinemia, in part by oppositely modulating hepatic and pancreatic PCSK9 secretion.
Assuntos
Hiperlipidemias/prevenção & controle , Hipolipemiantes/uso terapêutico , Fígado/metabolismo , Pâncreas/metabolismo , Pró-Proteína Convertase 9/metabolismo , Quercetina/análogos & derivados , Receptores de LDL/metabolismo , Animais , Linhagem Celular Tumoral , Colesterol na Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Regulação da Expressão Gênica , Transportador de Glucose Tipo 2/agonistas , Transportador de Glucose Tipo 2/antagonistas & inibidores , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 2/metabolismo , Hiperinsulinismo/sangue , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Hiperinsulinismo/prevenção & controle , Hiperlipidemias/sangue , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Hipolipemiantes/administração & dosagem , Hipolipemiantes/efeitos adversos , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Especificidade de Órgãos , Pâncreas/patologia , Pró-Proteína Convertase 9/sangue , Pró-Proteína Convertase 9/genética , Quercetina/administração & dosagem , Quercetina/efeitos adversos , Quercetina/uso terapêutico , Receptores de LDL/genéticaRESUMO
We reported that PIM1 kinase is expressed in the lymphocytes of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Quercetin, a naturally occurring flavonoid, is a dietary supplement and inhibits many kinases, including PIM1, in vitro. Under an Institutional Review Board-approved protocol, we performed an open-label, single-arm pilot study to evaluate the antitumor activity of quercetin in patients with CLL/SLL. Q-ForceTM chews were administered orally, 500 mg twice daily, for 3 months. Eligible patients had failed prior therapies, had had no other standard treatment, or refused other therapies. Response was assessed based on objective change in disease parameters. Patients were included if their lymphocyte counts were rising and ≥10,000/µL but not > 100,000/µL. Three patients received quercetin treatment. There was no toxicity. Two responded with stabilization of rising lymphocyte counts (p < 0.001 for each), which remained stable during their follow-up (5 and 11 months after cessation of treatment, respectively). The CLL cells in the nonresponder harbored a TP53 mutation. Although our data from this pilot translational study are based on a small sample, further studies of quercetin as a potential therapeutic agent in selected patients with CLL/SLL appear warranted.
Assuntos
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Quercetina/uso terapêutico , Idoso , Biomarcadores , Suplementos Nutricionais , Feminino , Humanos , Imuno-Histoquímica , Leucemia Linfocítica Crônica de Células B/mortalidade , Pessoa de Meia-Idade , Seleção de Pacientes , Projetos Piloto , Quercetina/administração & dosagem , Quercetina/efeitos adversos , Resultado do TratamentoRESUMO
The flavonoid quercetin is frequently found in low amounts as a secondary plant metabolite in fruits and vegetables. Isolated quercetin is also marketed as a dietary supplement, mostly as the free quercetin aglycone, and frequently in daily doses of up to 1000 mg d-1 exceeding usual dietary intake levels. The present review is dedicated to safety aspects of isolated quercetin used as single compound in dietary supplements. Among the numerous published human intervention studies, adverse effects following supplemental quercetin intake have been rarely reported and any such effects were mild in nature. Published adequate scientific data for safety assessment in regard to the long-term use (>12 weeks) of high supplemental quercetin doses (≥1000 mg) are currently not available. Based on animal studies involving oral quercetin application some possible critical safety aspects could be identified such as the potential of quercetin to enhance nephrotoxic effects in the predamaged kidney or to promote tumor development especially in estrogen-dependent cancer. Furthermore, animal and human studies with single time or short-term supplemental quercetin application revealed interactions between quercetin and certain drugs leading to altered drug bioavailability. Based on these results, some potential risk groups are discussed in the present review.
Assuntos
Suplementos Nutricionais/efeitos adversos , Quercetina/administração & dosagem , Quercetina/efeitos adversos , Animais , Interações Medicamentosas , Humanos , Rim/efeitos dos fármacos , Quercetina/metabolismo , Reprodução/efeitos dos fármacosRESUMO
BACKGROUND: The constant pursuit of improved athletic performance characterizes high-performance sport and the use of medicinal plants as dietary supplements is becoming widespread among athletes to enhance long-term endurance performance. AIM: The present study evaluated the toxicity of Heteropterys tomentosa (HEHt) and its acute adaptogenic effects. METHODS: The in vitro safety profile was evaluated on CHO-k1 cells using the alamar Blue assay, at concentrations ranging from 3.125 to 200 µg/mL. In vivo acute oral toxicity was conducted in male and female mice with oral administration of graded doses of HEHt from 400 to 2000 mg/kg. A subchronic oral toxicity study was completed by oral administration of HEHt (50, 200 or 1000 mg/kg) and vehicle for 30 days in male Wistar rats. Clinical observations and toxicological related parameters were determined. Blood was collected for biochemical and hematological analyses, while histological examinations were performed on selected organs. Thereafter, an adaptogenic test consisting of progressive loads until exhaustion was conducted in rats ( n = 5/group) orally pre-treated with the vehicle and HEHt (25, 100 or 400 mg/kg). RESULTS: HEHt exhibited no cytotoxic effects on the CHO-k1 cells and, apparently, no acute toxicity in mice and no subchronic toxicity in rats. An ergogenic effect was observed only at the dose of 25 mg/kg compared with the vehicle in relation to time to exhaustion and exercise load ( p = .011 and .019, respectively). HEHt is safe at up to 400 mg/kg, contains astilbin and taxifolin as the major phytochemical compounds, and exhibited a potential adaptogenic effect. CONCLUSIONS: These results justify its anecdotal usage as a tonic, show that the hydroethanolic maceration of the root does not cause toxicity, and provide scientific evidence of its potential as a source of new adaptogenic substance(s).
Assuntos
Suplementos Nutricionais/efeitos adversos , Malpighiaceae/química , Substâncias para Melhoria do Desempenho/efeitos adversos , Extratos Vegetais/efeitos adversos , Raízes de Plantas/química , Animais , Comportamento Animal , Células CHO , Cricetulus , Etnofarmacologia , Fadiga/etiologia , Fadiga/prevenção & controle , Feminino , Flavonóis/administração & dosagem , Flavonóis/efeitos adversos , Flavonóis/metabolismo , Flavonóis/uso terapêutico , Masculino , Malpighiaceae/crescimento & desenvolvimento , Medicina Tradicional , Camundongos , Substâncias para Melhoria do Desempenho/administração & dosagem , Substâncias para Melhoria do Desempenho/metabolismo , Substâncias para Melhoria do Desempenho/uso terapêutico , Esforço Físico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico , Raízes de Plantas/crescimento & desenvolvimento , Quercetina/administração & dosagem , Quercetina/efeitos adversos , Quercetina/análogos & derivados , Quercetina/metabolismo , Quercetina/uso terapêutico , Distribuição Aleatória , Ratos Wistar , Testes de Toxicidade Aguda , Testes de Toxicidade SubcrônicaRESUMO
Helicobacter pylori-associated gastritis is a major threat to public health and Polygonum capitatum (PC) may have beneficial effects on the disease. However, the molecular mechanism remains unknown. Quercetin was isolated from PC and found to be a main bioactive compound. The effects of quercetin on human gastric cancer cells GES-1 were determined by xCELLigence. H. pylori-infected mouse models were established. All mice were divided into three groups: control (CG, healthy mice), model (MG, H. pylori infection) and quercetin (QG, mouse model treated by quercetin) groups. IL-8 (interleukin-8) levels were detected via enzyme-linked immunosorbent assay (ELISA). Cell cycle and apoptosis were measured by flow cytometry (FCM). Quantitative reverse transcription PCR (qRT-PCR) and Western Blot were used to detect the levels of p38MAPK (38-kD tyrosine phosphorylated protein kinase), apoptosis regulator BCL-2-associated protein X (BAX) and B cell lymphoma gene 2 (BCL-2). The levels of IL-8 were increased by 8.1-fold in a MG group and 4.3-fold in a QG group when compared with a CG group. In a MG group, G0-G1(phases of the cell cycle)% ratio was higher than a CG group while S phase fraction was lower in a model group than in a control group (p < 0.01). After quercetin treatment, G0-G1% ratio was lower in a QG group than a MG group while S phase fraction was higher than a MG group (p < 0.01). Quercetin treatment reduced the levels of p38MAPK and BAX, and increased the levels of BCL-2 when compared with a MG group (p < 0.05). Quercetin regulates the balance of gastric cell proliferation and apoptosis to protect against gastritis. Quercetin protects against gastric inflammation and apoptosis associated with H. pylori infection by affecting the levels of p38MAPK, BCL-2 and BAX.
Assuntos
Gastrite/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Extratos Vegetais/química , Polygonum/química , Quercetina/química , Quercetina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular , Infecções por Helicobacter/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Interleucina-8/metabolismo , Masculino , Camundongos , Fosforilação , Extratos Vegetais/isolamento & purificação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quercetina/administração & dosagem , Quercetina/efeitos adversos , Ratos , Sementes/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Nowadays dietary flavonoids attract much attention in the prevention of chronic diseases. Epidemiological and intervention studies strongly suggest that flavonoid intake has beneficial effects on vascular health. It is unlikely that flavonoids act as direct antioxidants, although oxidative stress profoundly contributes to vascular impairment leading to cardiovascular diseases. Instead, flavonoids may exert their function by tuning the cellular redox state to an adaptive response or tolerable stress. However, the optimum intake of flavonoids from supplements or diet has not been clarified yet, because a number of exogenous and endogenous factors modulating their bioavailability affect their vascular function. This review will focus on the current knowledge of the bioavailability and vascular function of quercetin as a representative of antioxidative flavonoids. Current intervention studies imply that intake of quercetin-rich onion improves vascular health. Onion may be superior to quercetin supplement from the viewpoint of quercetin bioavailability, probably because the food matrix enhances the intestinal absorption of quercetin. α-Glucosylation increases its bioavailability by elevating the accessibility to the absorptive cells. Prenylation may enhance bioaccumulation at the target site by increasing the cellular uptake. However, these chemical modifications do not guarantee health benefits to the vascular system. Dietary quercetin is exclusively present as their conjugated form in the blood stream. Quercetin may exert its vascular function as an aglycone within macrophage cells after inflammation-induced deconjugation and as conjugated metabolites by targeting endothelial cells. The relationship between the bioavailability and bio-efficacy should be clarified, to evaluate the vascular function of a wide variety of dietary flavonoids.
Assuntos
Dieta Saudável , Suplementos Nutricionais , Endotélio Vascular/fisiologia , Flavonoides/uso terapêutico , Absorção Intestinal , Quercetina/análogos & derivados , Doenças Vasculares/prevenção & controle , Absorção Fisiológica , Animais , Antioxidantes/efeitos adversos , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Vasos Sanguíneos/imunologia , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiologia , Vasos Sanguíneos/fisiopatologia , Suplementos Nutricionais/efeitos adversos , Digestão , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Flavonoides/efeitos adversos , Flavonoides/sangue , Flavonoides/metabolismo , Microbioma Gastrointestinal , Glicosilação , Humanos , Hidrólise , Macrófagos/imunologia , Macrófagos/metabolismo , Estresse Oxidativo , Prenilação , Quercetina/efeitos adversos , Quercetina/metabolismo , Quercetina/uso terapêutico , Doenças Vasculares/imunologia , Doenças Vasculares/metabolismo , Doenças Vasculares/fisiopatologiaRESUMO
OBJECTIVE: To assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. STUDY DESIGN: This was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with <2 infective episodes in the 6-month follow-up and <3 episodes in the 12-month follow-up (main aim definition) and the reduction of related symptoms through a Visual Analog Scale (VAS) and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Student's t-test and chi-squared test were used for data analysis as appropriate. RESULTS: At 6-month follow up, the main aim rate was 8%, 11.1% and 25% in the three groups, respectively (p<0.05 compared to baseline only in group 3). Although the reduction in the number of recurrent episodes became significant in all groups at 1 year follow-up, the main aim rate was almost double in women receiving both local estrogens and oral therapy (group 3) compared to those receiving single treatments. The improvement of related symptoms was significant in all groups at 12-month follow-up. CONCLUSIONS: In postmenopausal women, the combination of HA, CS, curcumin and quercetin per os was effective in preventing recurrent urinary tract infections, especially if administered with vaginal estrogen therapy.
Assuntos
Envelhecimento , Sulfatos de Condroitina/uso terapêutico , Curcumina/uso terapêutico , Suplementos Nutricionais , Ácido Hialurônico/uso terapêutico , Quercetina/uso terapêutico , Infecções Urinárias/prevenção & controle , Anti-Infecciosos Urinários/efeitos adversos , Anti-Infecciosos Urinários/uso terapêutico , Antioxidantes/efeitos adversos , Antioxidantes/uso terapêutico , Vaginite Atrófica/complicações , Vaginite Atrófica/tratamento farmacológico , Vaginite Atrófica/fisiopatologia , Sulfatos de Condroitina/efeitos adversos , Terapia Combinada/efeitos adversos , Curcumina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Resistência à Doença/efeitos dos fármacos , Estriol/efeitos adversos , Estriol/uso terapêutico , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios/efeitos adversos , Estrogênios/uso terapêutico , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Pessoa de Meia-Idade , Pós-Menopausa , Quercetina/efeitos adversos , Prevenção Secundária , Índice de Gravidade de Doença , Infecções Urinárias/complicações , Infecções Urinárias/microbiologia , Infecções Urinárias/urina , Cremes, Espumas e Géis Vaginais/efeitos adversos , Cremes, Espumas e Géis Vaginais/uso terapêuticoRESUMO
In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.
Assuntos
Anti-Inflamatórios/uso terapêutico , Suplementos Nutricionais , Sistema Imunitário/efeitos dos fármacos , Inflamação/prevenção & controle , Quercetina/uso terapêutico , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacocinética , Disponibilidade Biológica , Dieta , Suplementos Nutricionais/efeitos adversos , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Absorção Intestinal , Quercetina/administração & dosagem , Quercetina/efeitos adversos , Quercetina/farmacocinética , Recomendações Nutricionais , Resultado do TratamentoRESUMO
BACKGROUND: Paraoxonase 1 (PON1) protects the oxidative modification of low-density lipoprotein (LDL) and is a major anti-atherosclerotic protein component of high-density lipoprotein. We explored the effect of onion extract and flavonoids (quercetin and catechin) in the regulation of PON1 expression and correlating with oxidised LDL levels in male Wistar rats subjected to mercuric chloride (HgCl2) induced oxidative insult. Rats were divided into eight groups: Control, Experimental (HgCl2), Experimental + onion/catechin/quercetin, Positive control (Normal + onion/catechin/quercetin). Treatment continued for 4 weeks. RESULTS: PON1 activity and radical scavenging activity decreased in the Experimental group (P < 0.001) with increased susceptibility of LDL for oxidation and plasma malondialdehyde levels (P < 0.001). Onion extract significantly attenuated the adverse effects of HgCl2 by up-regulating PON1 activity (P < 0.05), radical scavenging activity (P < 0.01), and protected against LDL oxidation (P < 0.001) and lipid peroxidation (P < 0.01). Similar effects were observed with quercetin and to a lesser extent with catechin. CONCLUSIONS: The findings may explain the anti-atherosclerotic effect of onion and also foods containing quercetin and catechins.
Assuntos
Antioxidantes/uso terapêutico , Aterosclerose/prevenção & controle , Catequina/uso terapêutico , Suplementos Nutricionais , Cebolas/química , Extratos Vegetais/uso terapêutico , Quercetina/uso terapêutico , Animais , Antioxidantes/efeitos adversos , Arildialquilfosfatase/sangue , Arildialquilfosfatase/química , Aterosclerose/sangue , Aterosclerose/enzimologia , Biomarcadores/sangue , Catequina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Índia , Peroxidação de Lipídeos , Lipoproteínas LDL/análise , Lipoproteínas LDL/antagonistas & inibidores , Masculino , Cebolas/economia , Estresse Oxidativo , Fitoterapia/efeitos adversos , Extratos Vegetais/efeitos adversos , Raízes de Plantas/química , Quercetina/efeitos adversos , Distribuição Aleatória , Ratos Wistar , Regulação para CimaRESUMO
BACKGROUND: Onion peel contains a high amount of quercetin, which has been reported to have anti-cholesterol, antithrombotic and insulin-sensitizing properties. This study aimed to elucidate the anti-adipogenic effects of quercetin-rich onion peel extract (OPE) and to compare it with commercially available quercetin using 3T3-L1 preadipocytes. RESULTS: Without affecting cell viability, both OPE and quercetin averted adipogenesis, as characterized by dose-dependent decreases in intracellular triglyceride content and glycerol 3-phosphate dehydrogenase activity, but the effect was more pronounced with OPE than with quercetin. The mRNA expression levels of key adipogenic genes such as PPARγ, C/EBPα, FABP4, aP2 and LPL were decreased in a dose-dependent manner by both OPE and quercetin. CONCLUSION: The results indicate that OPE treatment significantly prevents intracellular lipid accumulation via hyperactivation of genes regulating lipolysis as compared with quercetin alone.
Assuntos
Adipogenia , Fármacos Antiobesidade/metabolismo , Cebolas/química , Epiderme Vegetal/química , Extratos Vegetais/metabolismo , Raízes de Plantas/química , Quercetina/metabolismo , Células 3T3-L1 , Adipócitos Brancos/citologia , Adipócitos Brancos/metabolismo , Animais , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/química , Proteínas Estimuladoras de Ligação a CCAAT/antagonistas & inibidores , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Sobrevivência Celular , Suplementos Nutricionais , Regulação para Baixo , Regulação da Expressão Gênica , Lipólise , Camundongos , PPAR gama/antagonistas & inibidores , PPAR gama/genética , PPAR gama/metabolismo , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Quercetina/efeitos adversos , Quercetina/análise , República da Coreia , Triglicerídeos/metabolismoRESUMO
Longevinex, a nutraceutical formulation containing Resveratrol as the main component along with other polyphenolics exhibits diverse health benefits but systemic safety studies are lacking. Hence, to test the safety of Longevinex use for therapeutic purposes, 50 Sprague Dawley rats were randomly divided into five groups (n=10; 5M, 5F) wherein group I as vehicle treated control, group II and group III received 50 mg and 100 mg of plain Resveratrol respectively and group IV and group V received 50 mg and 100 mg of Longevinex respectively for a period of 28 days. All toxicological parameters were analyzed as per OECD-407 guidelines. Results showed treatment with Resveratrol and Longevinex did not result in any mortality of rats neither did they exhibit any clinical signs of toxicity. Hematological and biochemical analysis of serum enzymes and metabolites were not significantly altered between Longevinex and control rats. Likewise, histopathological analysis for various organs did not reveal significant changes in the vital organs of the treated rats. The study revealed that there were no significant treatment related adverse effects in rats exposed to Longevinex for 28 days and considered safe at the given dose where compared to plain Resveratrol.
Assuntos
Antioxidantes/efeitos adversos , Ácidos Cumáricos/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Ácido Fítico/efeitos adversos , Quercetina/efeitos adversos , Estilbenos/efeitos adversos , Animais , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Cardiotônicos/administração & dosagem , Cardiotônicos/efeitos adversos , Cardiotônicos/química , Ácidos Cumáricos/administração & dosagem , Ácidos Cumáricos/química , Suplementos Nutricionais/análise , Feminino , Masculino , Nível de Efeito Adverso não Observado , Ácido Fítico/administração & dosagem , Ácido Fítico/química , Quercetina/administração & dosagem , Quercetina/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Resveratrol , Estilbenos/administração & dosagem , Estilbenos/química , Testes de Toxicidade SubagudaRESUMO
Dietary plant flavonoids have been proposed to contribute to cancer prevention, neuroprotection, and cardiovascular health through their anti-oxidant, anti-inflammatory, pro-apoptotic, and antiproliferative activities. As a consequence, flavonoid supplements are aggressively marketed by the nutraceutical industry for many purposes, including pediatric applications, despite inadequate understanding of their value and drawbacks. We show that two flavonoids, luteolin and quercetin, are promiscuous endocrine disruptors. These flavonoids display progesterone antagonist activity beneficial in a breast cancer model but deleterious in an endometrial cancer model. Concurrently, luteolin possesses potent estrogen agonist activity while quercetin is considerably less effective. These results highlight the promise and peril of flavonoid nutraceuticals and suggest caution in supplementation beyond levels attained in a healthy, plant-rich diet.