isoquercitrin and Disease-Models--Animal

The flavonoid isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is commonly found in medicinal herbs, fruits, vegetables and plant-derived foods and beverages. This article reviews the occurrence, preparation, bioavailability, pharmacokinetics, toxicology and biological activity of isoquercitrin and "enzymatically modified (α-glucosylated) isoquercitrin" (EMIQ). Pure isoquercitrin can now be obtained on a large scale by enzymatic rutin hydrolysis with α-l-rhamnosidase. Isoquercitrin has higher bioavailability than quercetin and displays a number of chemoprotective effects both in vitro and in vivo, against oxidative stress, cancer, cardiovascular disorders, diabetes and allergic reactions. Although small amounts of intact isoquercitrin can be found in plasma and tissues after oral application, it is extensively metabolized in the intestine and the liver. Biotransformation of isoquercitrin includes deglycosylation, followed by formation of conjugated and methylated derivatives of quercetin or degradation to phenolic acids and carbon dioxide. The acceptable daily intake of (95%) isoquercitrin and of EMIQ was estimated to be 5.4 and 4.9mg/kg/day, respectively. Adverse effects of higher doses in rats included mostly (benign) chromaturia; nevertheless some drug interactions may occur due to the modulation of the activity and/or expression of drug metabolizing/transporting systems. With respect to the safety, affordability and beneficial pharmacological activities, highly pure isoquercitrin is a prospective substance for food supplementation.

Topics: Animals; Biological Availability; Biotransformation; Chemical Phenomena; Chemoprevention; Disease Models, Animal; Humans; Quercetin

The aerial parts of Tilia americana var. mexicana (Malvaceae, formerly Tiliaceae) or "sirimo" are used in Mexican traditional medicine for the relief of mild symptoms of mental stress, commonly referred to as "nerve diseases". Individuals use this plant to fall asleep, to calm states of nervous excitement, headaches, mood disorders, and general discomfort. Recent studies indicated that fractions standardized in their flavonoid content possess antidepressant activity in behavioral assays in mice. The present study aims to focus on the evaluation of the antidepressant effect of the mixture of two flavonoids (FMix), and its interaction with serotonergic drugs. Also, the pharmacological effect of the products of the metabolism of aglycone, quercetin, was evaluated in mice subjected to forced swimming test (FST) and open field test (OFT).. A methanol-soluble extract obtained from leaves of Tilia americana was fractionated in an open column chromatographic separation. One of the fractions contained FMix wich is constituted of the mixture of quercetin 4'-O-rhamnoside (1, 47%) y isoquercitrin (2, 53%). The mice were divided into the several following groups: FMix (0.01, 0.1, 0.5, 1.0, and 2 mg/kg); FMix (1.0 mg/kg) and agonist DOI (2.0 mg/kg); FMix (1.0 mg/kg) and antagonist ketanserin (KET, 0.03 mg/kg) of 5-HT2A receptors; FMix (1.0 mg/kg) and selective agonist 8-OH-DPAT (8-OH, 0.01 mg/kg); FMix (1.0 mg/kg) and antagonist WAY100635 (WAY, 0.5 mg/kg) of 5HT1 receptors; Phloroglucinol (PHL); 3,4-dihydroxy-phenyl acid (DOPAC); p-hydroxyphenyl acetic acid (p-HPAA); and m-hydroxyphenyl acetic acid (m-HPAA) were tested in FST or OFT.. FMix induced dependent-dose antidepressant activity and, at the highest dose administered, a sedative effect was also observed. The 8-OH-DPAT, or the DOI, or the KET combination with FMix (1.0 mg/kg) induced a higher antidepressant effect than compounds alone; there was no effect exerted with WAY. The activity on OFT increased only with the FMix and KET combination. At the same time, the products of the aglycone metabolism of quercetin, that is, DOPAC and p-HPAA, decreased the immobility time of the mice in FST at 1.0 mg/kg, and a dose-curve was formed for these.. The antidepressant effect of FMix could depend, at least in part, on the degradation products of quercetin and with a possible action mode through interaction with the serotoninergic system.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Biotransformation; Brain; Depression; Disease Models, Animal; Exploratory Behavior; Male; Mice, Inbred ICR; Motor Activity; Plant Extracts; Quercetin; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Serotonergic Neurons; Serotonin; Tilia

Anaphylaxis is a life-threatening allergic reaction, for which the worldwide prevalence is rapidly increasing. The currently used synthetic antiallergic drugs have a high tendency to cause adverse effects, like gastric ulcers, in long-term use. Therefore, a great deal of attention has been given to develop new safer and more effective antiallergic agents from natural compounds that are chemically/enzymatically-modified. Here, we evaluated/compared the efficacy of two different doses (50 and 100 mg/kg body weight "b.w", given orally) of sodium R-lipoate (NaRLA) and enzymatically-modified isoquercitrin (EMIQ) in alleviating both local/systemic non-immunological anaphylactic reactions and stress-induced gastric ulceration in mice, in comparison with sulfasalazine (SSZ) as a reference drug. The results indicated that the pre-treatment of animals with NaRLA or EMIQ (especially at 100 mg/kg b.w) completely succeeded, as SSZ, in alleviating the hind paw edema induced by either histamine or compound 48/80 (Cpd 48/80). Furthermore, NaRLA and EMIQ prevented the mast cell degranulation and anaphylactic shock caused by Cpd 48/80 (in a dose-dependent manner) and reduced significantly (P < 0.001) the histamine release from the mouse peritoneal mast cells, like SSZ. Moreover, their use was associated with alleviating both gastric histopathological and biochemical alterations in the water-restraint stress (WRS) mice model towards the control values. They also decreased the percentage of degranulated mesenteric mast cells in the WRS mice model. In conclusion, our findings provide possibility that both NaRLA and EMIQ may serve as an effective therapeutic agents for mast cells-dependent anaphylactic reactions without risks of inducing gastric ulcers.

Topics: Administration, Oral; Anaphylaxis; Animals; Anti-Allergic Agents; Cell Degranulation; Disease Models, Animal; Gastric Mucosa; Histamine Release; Humans; Male; Mast Cells; Mice; p-Methoxy-N-methylphenethylamine; Quercetin; Specific Pathogen-Free Organisms; Stomach Ulcer; Stress, Psychological; Sulfasalazine; Thioctic Acid

Parkinson's disease is the second most common neurodegenerative disease. Researchers have shown that oxidative stress and apoptosis play an important role in the Parkinson's disease process. Isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is a natural flavonol compound and one of the main active ingredients of agricultural waste apple pomace. Increasing evidence indicates that this compound possesses anti-oxidation, anti-aging, and anti-inflammation properties. In this study, isoquercitrin was purified from apple pomace by high-speed countercurrent chromatography and its neuroprotective effect on Parkinson's disease was investigated in MPTP-induced acute mouse models. It was found that isoquercitrin ameliorated the animal behaviors against MPTP-induced neurotoxicity, mitigated the loss of dopamine neurons induced by MPTP, increased tyrosine hydroxylase and dopamine transporter expression, reduced the pro-apoptotic signaling molecule bax expression and inhibited MPTP-triggered oxidative stress. Our results demonstrated that isoquercitrin has protective effects on the MPTP subacute model mouse, which might be partially mediated through the actions of anti-oxidation and anti-apoptosis. Isoquercitrin might be a new promising protective drug for the improvement of Parkinson's disease.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Apoptosis; Countercurrent Distribution; Disease Models, Animal; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Humans; Male; Malus; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidative Stress; Parkinson Disease; Quercetin; Tyrosine 3-Monooxygenase

Diabetic neuropathy is a peripheral nervous system disorder affecting both somatic and autonomic components of nervous system. A growing body of evidence have depicted that high glucose levels can induce activation of the Wnt/β-catenin pathway, however there are no studies targeting this pathway in DN. The intent of the present study was to investigate the effects of isoquercitrin (ISQ), a Wnt/β-catenin signaling pathway inhibitor, in diabetic neuropathy. Streptozotocin (50 mg/kg, i.p.) was used to induce diabetes in rats. 6-week diabetic rats were treated intrathecally with ISQ at 10 and 30 μM doses for 3 days. Furthermore, to confirm the results of the intrathecal study, a 2-week intraperitoneal treatment of ISQ was given to diabetic rats. After 6 weeks, diabetic rats developed neuropathy which was evident from reduced thermal and mechanical hyperalgesia thresholds and significant deterioration in motor nerve conduction velocity (MNCV), nerve blood flow (NBF). Sciatic nerves of diabetic neuropathy rats showed increased expression of Wnt pathway proteins namely β-catenin, c-myc and MMP2. Treatment with ISQ, both intrathecally (10 and 30 μM) and intraperitoneally (10 mg/kg), significantly ameliorated the alterations in behavioral pain thresholds and improved functional parameters in diabetic rats. Moreover, ISQ also downregulated the expression of Wnt/β-catenin pathway proteins significantly in diabetic rats as compared to vehicle-treated diabetic rats. Results of the present study suggest the neuroprotective potential of ISQ in the treatment of DN via inhibition of Wnt/β-catenin signaling pathway.

Topics: Animals; Antioxidants; Catenins; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Disease Models, Animal; Male; Neuroprotective Agents; Quercetin; Rats; Rats, Sprague-Dawley; Wnt Signaling Pathway

Topics: Acer; Adipokines; Adiponectin; Administration, Ophthalmic; Alzheimer Disease; Amyloid Precursor Protein Secretases; Amyloidosis; Animals; Brain; Diet, High-Fat; Disease Models, Animal; Leptin; Obesity; Phytotherapy; Plant Extracts; Presenilin-1; Quercetin

Obesity induced by high-fat diet (HFD) and accumulation of amyloid beta (Aβ) are known as a risk factor of Alzheimer's disease. We previously identified isoquercitrin (IQ) as an active compound of Acer okamotoanum. In the present study, we investigated the protective effects of the active ethyl acetate (EtOAc) fraction from A. okamotoanum and IQ on HFD and Aβ25-35-induced cognitive impairment mice. C57BL/6J mice were fed with HFD for 10 weeks and then Aβ25-35 was injected intracerebroventricularly (i.c.v.). The EtOAc fraction of A. okamotoanum and IQ were administered orally for 4 weeks at 100 and 10 mg kg-1 day-1, respectively. Learning and memory functions were evaluated using behavioral tests including T-maze, object recognition and Morris water maze tests. The HFD and Aβ25-35 injection significantly impaired cognitive and memory function. However, administration of A. okamotoanum and IQ improved spatial cognitive ability and object recognition ability in T-maze and novel object recognition tests. In addition, A. okamotoanum and IQ-administered groups showed enhanced learning and memory function compared with HFD and Aβ25-35-induced cognitive impairment mice in the Morris water maze test. Furthermore, administration of A. okamotoanum and IQ attenuated oxidative stress in the brain via inhibition of reactive oxygen species production, lipid peroxidation, and nitric oxide formation. Therefore, we suggest that A. okamotoanum and IQ improve HFD- and Aβ25-35-induced cognitive impairment by inhibition of oxidative stress, and A. okamotoanum and IQ might be potential candidates for prevention and treatment of obesity- and Aβ-induced cognitive impairment.

Topics: Acer; Administration, Oral; Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Cognition; Cognitive Dysfunction; Diet, High-Fat; Disease Models, Animal; Lipid Peroxidation; Male; Maze Learning; Memory; Mice; Mice, Inbred C57BL; Oxidative Stress; Peptide Fragments; Plant Extracts; Quercetin

Mineralocorticoid receptor (MR)/NADPH oxidase (NOX) signaling is involved in the development of obesity, insulin resistance, and renal diseases; however, the role of this signaling on steatotic preneoplastic liver lesions is not fully elucidated. We determined the effects of the MR antagonist potassium canrenoate (PC) on MR/NOX signaling in hepatic steatosis and preneoplastic glutathione S-transferase placental form (GST-P)-positive liver foci. Rats were subjected to a two-stage hepatocarcinogenesis model and fed with basal diet or high fat diet (HFD) that was co-administered with PC alone or in combination with the antioxidant alpha-glycosyl isoquercitrin (AGIQ). PC reduced obesity and renal changes (basophilic tubules that expressed MR and p22phox) but did not affect blood glucose tolerance and non-alcoholic fatty liver disease activity score (NAS) in HFD-fed rats. However, the drug increased the area of GST-P-positive liver foci that expressed MR and p22phox as well as increased expression of NOX genes (p22phox, Poldip2, and NOX4). PC in combination with AGIQ had the potential of inhibiting the effects of PC on the area of GST-P-positive liver foci and the effects were associated with increasing expression of an anti-oxidative enzyme (Catalase). The results suggested that MR/NOX signaling might be involved in development of preneoplastic liver foci and renal basophilic changes in HFD-fed rats; however, the impacts of PC were different in each organ.

Topics: Animals; Antioxidants; Canrenoic Acid; Catalase; Diet, High-Fat; Disease Models, Animal; Gene Expression; Glutathione S-Transferase pi; Kidney; Liver; Liver Neoplasms; Mineralocorticoid Receptor Antagonists; NADPH Oxidases; Organ Specificity; Quercetin; Receptors, Mineralocorticoid; Signal Transduction

Isoquercetin (IQ), a glucoside derivative of quercetin, has been reported to have beneficial effects in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the potential improvement of IQ in liver lipid accumulation, inflammation, oxidative condition, and activation in Kupffer cells (KCs) on a high-fat diet (HFD) induced NAFLD models. Male Sprague-Dawley (SD) rats were induced by HFD, lipopolysaccharides/free fatty acids (LPS/FFA) induced co-culture cells model between primary hepatocytes and Kupffer cells was used to test the effects and the underlying mechanism of IQ. Molecular docking was performed to predict the potential target of IQ. Significant effects of IQ were found on reduced lipid accumulation, inflammation, and oxidative stress. In addition, AMP-activated protein kinase (AMPK) pathway was activated by IQ, and is plays an important role in lipid regulation. Meanwhile, IQ reversed the increase of activated KCs which caused by lipid overload, and also suppression of Transforming growth factor beta (TGF-β) signaling by TGF-β Recptor-1 and SMAD2/3 signaling. Finally, TGF-βR1 and TGF-βR2 were both found may involve in the mechanism of IQ. IQ can improve hepatic lipid accumulation and decrease inflammation and oxidative stress by its activating AMPK pathway and suppressing TGF-β signaling to alleviate NAFLD.

Topics: AMP-Activated Protein Kinases; Animals; Biomarkers; Coculture Techniques; Cytokines; Diet, High-Fat; Disease Models, Animal; Down-Regulation; Inflammation; Kupffer Cells; Lipid Metabolism; Liver; Male; Molecular Docking Simulation; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Phosphorylation; Protein Serine-Threonine Kinases; Quercetin; Rats, Sprague-Dawley; Signal Transduction; Transforming Growth Factor beta

Q3G is a natural derivative of quercetin and is already widely used in various foods and drinks. Our results clearly demonstrated that Q3G exerts antiviral activity against ZIKV in both tissue culture and knockout mice, and that post-exposure in vivo treatment with Q3G could have a beneficial effect. In the future, Q3G should be tested in human cell lines (such as Huh-7, HeLa, or K048, a fetal brain neural stem cell line) to provide further data supporting its potential efficacy in humans; in addition, live viral loads or viremia should be tested in treated animals to supplement the survival results observed in this study. Although the treatment regimens will need to be further optimized (i.e., dosage, frequency of treatment, and administration routes), our results support the results of Q3G efficacy studies in nonhuman primates against ZIKV infection. Further studies will also be needed to investigate the mechanism of Q3G antiviral action, in order to obtain valuable insights into the design of novel targets for antiviral therapeutics in the future.

Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Disease Models, Animal; Mice, Knockout; Quercetin; Survival Analysis; Vero Cells; Viral Load; Virus Replication; Zika Virus; Zika Virus Infection

We determined effects of the NADPH oxidase (NOX) inhibitor apocynin (APO) or the antioxidant enzymatically modified isoquercitrin (EMIQ) on an early stage of hepatocarcinogenesis in the liver with steatosis. Male rats were given a single intraperitoneal injection of N-diethylnitrosamine (DEN) and fed a high-fat diet (HFD) to subject to a two-stage hepatocarcinogenesis model. Two weeks later, rats were fed a HFD containing the lipogenic substance malachite green (MG), which were co-administered with EMIQ or APO in drinking water for 6 weeks. Three after DEN initiation, rats were subjected to a two-third partial hepatectomy to enhance cell proliferation. The HFD increased total cholesterol and alkaline phosphatase levels, which were reduced by EMIQ co-administration. APO co-administration reduced MG-increased preneoplastic liver lesions, glutathione S-transferase placental form (GST-P)-positive, adipophilin-negative liver foci, and tended to decrease MG-increased Ki-67-positive or active caspase-3-positive cells in the liver foci. EMIQ or APO co-administration reduced the expression of a NOX subunit p22phox in the liver foci, but did not alter the numbers of LC3a-positive cells, an autophagy marker. We identified no treatment-related effects on p47phox and NOX4 expression in the liver foci. The results indicated that APO or EMIQ had the potential to suppress hyperlipidaemia and steatosis-preneoplastic liver lesions, through suppression of NOX subunit expression in rats.

Topics: Acetophenones; Animals; Carcinogenesis; Disease Models, Animal; Enzyme Inhibitors; Fatty Liver; Immunohistochemistry; Liver; Liver Neoplasms, Experimental; Male; NADPH Oxidases; Precancerous Conditions; Quercetin; Rats; Rats, Inbred F344

Pulmonary vascular remodelling is a common feature among the heterogeneous disorders that cause pulmonary arterial hypertension (PAH), and pulmonary arterial smooth muscle cells (PASMCs) proliferation impact the long-term prognosis of the patient. Isoquercitrin (IQC) is a flavonoid with anti-oxidative, anti-inflammatory and anti-proliferative activations. This study aimed to investigate whether IQC could prevent PASMCs proliferation and vascular remodelling in monocrotaline (MCT) induced PAH. Male Wistar rats were administered with Vehicle or 0.1% IQC maintain feed after MCT (40 mg/kg) injection. Haemodynamic changes, right ventricular hypertrophy and lung morphological features were assessed 3 weeks later. MCT-induced PAH, pulmonary vascular remodelling and PASMCs proliferation in Vehicle-treated rats. IQC reduced the right ventricle systolic pressure (RVSP), the ratio of RV/LV+S and the RV hypertrophy. IQC significantly alleviated the expression of proliferating cell nuclear antigen (PCNA), smooth muscle α-actin (α-SMA), and the percentage of fully muscularized small arterioles. In vitro studies, PASMCs were pretreated with IQC and stimulated with platelet-derived growth factor (PDGF)-BB (20 ng/mL). IQC suppressed PDGF-BB-induced PASMCs proliferation and caused G0/G1 phase cell cycle arrest. IQC downregulated the expression of Cyclin D1 and CDK4 as well as inhibited p27Kip1 degradation. Meanwhile, IQC negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, Akt/GSK3β and ERK1/2. IQC ameliorated MCT-induced pulmonary vascular remodelling via suppressing PASMCs proliferation and blocking PDGF-Rβ signalling pathway.

Topics: Animals; Antioxidants; Cell Cycle Checkpoints; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p27; Disease Models, Animal; Flow Cytometry; Hypertension, Pulmonary; Male; Myocytes, Smooth Muscle; Pulmonary Artery; Quercetin; Rats, Wistar; Vascular Remodeling

Developing effective treatments and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients' health. It has been suggested that platelet activation and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0.3% CZ, 1.5% EMIQ, and 0.2% ALA in their feed. Colitis was induced by administering 5% DSS in drinking water for 8days. The inhibitory effects of these substances were evaluated by measuring relevant clinical symptoms (faecal blood, diarrhoea, and body weight loss), colon length, plasma cytokine and chemokine levels, whole genome gene expression, and histopathology. Diarrhoea was suppressed by each treatment, while CZ prevented shortening of the colon length. All treatment groups exhibited decreased plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α compared with the DSS group. Microarray analysis showed that cell adhesion, cytoskeleton regulation, cell proliferation, and apoptosis, which might be related to inflammatory cell infiltration and mucosal healing, were affected in all the groups. DSS-induced mucosal injuries such as mucosal loss, submucosal oedema, and inflammatory cell infiltration in the distal colon were prevented by CZ or antioxidant treatment. These results suggest that anti-inflammatory effects of these agents reduced DSS-induced mucosal injuries in mice and, therefore, may provide therapeutic benefits in IBD.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cilostazol; Colitis; Dextran Sulfate; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Oligonucleotide Array Sequence Analysis; Phosphodiesterase 3 Inhibitors; Quercetin; Tetrazoles; Thioctic Acid

Context Hypericum perforatum L. (Hypericaceae), used in moderate depression treatment, is active in experimental tests for antidepressant activity. For H. connatum Lam., a South American species lacking hyperforin, antidepressant effects have not been demonstrated. Objective This study evaluates the antidepressant-like effect of H. connatum in rats and identifies the components involved in this activity. Materials and methods First, the effects of acute and 14-d oral administrations of an extract derived from H. connatum aerial parts were studied using the Escape Deficit (ED) test. Next, methanol-extracted flavonoid-enriched fractions B and C and fraction-purified flavonoids (quercetin, rutin and isoquercitrin) were evaluated in the ED test after acute administration. To rule out possible confounding effects of the flavonoids, we examined nociceptive threshold using the tail-flick test and anxious behaviour using the elevated plus maze (EPM) test. Results Hypericum connatum increased reactivity of unavoidable stress-exposed rats after acute (0.5 and 1 g/kg: ED = 18.6/30 and 19.8/30, respectively) and repeated administration (0.5 g/kg twice daily: ED = 17.8/30). Protective effects were observed for fractions B and C (250 mg/kg: ED = 18.1/30 and 18.8/30, respectively), quercetin (2.5, 5 and 10 mg/kg: ED = 15.3/30, 18.3/30 and 21.6/30, respectively), rutin (5 and 10 mg/kg: ED = 15.4/30 and 13.0/30, respectively) and isoquercitrin (2.5 mg/kg: ED = 19.2/30). The flavonoids did not modify nociceptive threshold or performance in the EPM test. Discussion and conclusion Hypericum connatum showed protective activity in the ED test, a correlate of potential antidepressant-like effects that appeared to be related to the flavonoid components of this species.

Topics: Administration, Oral; Animals; Antidepressive Agents; Behavior, Animal; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Escape Reaction; Flavonoids; Hypericum; Locomotion; Male; Maze Learning; Nociception; Pain Threshold; Phytotherapy; Plant Components, Aerial; Plant Extracts; Plants, Medicinal; Quercetin; Rats, Sprague-Dawley; Rutin; Stress, Psychological

Dietary flavonoid intake shows a significant inverse association with mortality from coronary heart disease, incidence of myocardial infarction and stroke. Quercetin is one of the most common flavonoids in our diet and has several favorable biological activities. Quercetin glucosides, which are enzymatically trans-glycosylated isoquercitrin, have high water-solubility and bioavailability compared with quercetin. Here, we investigated the effects of quercetin glucosides on collateral development in a murine hindlimb ischemia model.. We induced hindlimb ischemia in 24- to 32-week-old male C3H/HeJ mice by resecting the right femoral artery. Then, 0.5% carboxymethyl cellulose (control) or quercetin glucosides (100mg/kg/day) were administered daily by gavage. Blood flow was monitored weekly by laser Doppler imaging.. Recovery of blood flow to the ischemic leg was significantly enhanced by quercetin glucosides (blood flow ratio at 4 weeks: control, 0.57 ± 0.11; quercetin glucosides, 0.95 ± 0.10, p<0.05). Furthermore, anti-CD31 immunostaining revealed that quercetin glucosides increased capillary density in the ischemic muscle (control, 200 ± 24/mm(2); quercetin glucosides, 364 ± 41/mm(2), p<0.01). Quercetin glucosides did not promote tumor growth. The beneficial effect of quercetin glucosides was abrogated in eNOS-deficient mice.. These results suggest that quercetin glucosides may have therapeutic potential to promote angiogenesis in ischemic tissue.

Topics: Angiogenesis Inducing Agents; Animals; Antioxidants; Capillaries; Cytokines; Disease Models, Animal; Glucosides; Hindlimb; Ischemia; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Mutant Strains; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic; Nitric Oxide Synthase Type III; Quercetin

Previous studies have shown that the extracts obtained from Tropaeolum majus L., and its main compound isoquercitrin (ISQ), exhibit pronounced diuretic effects, supporting the ethnopharmacological use of this plant. The aim of this study was to evaluate the efficacy and mechanisms underlying the diuretic action of an ethanolic extract of Tropaeolum majus (HETM), its purified fraction (TMLR), and its main compound ISQ, in spontaneously hypertensive rats (SHR).. The diuretic effects of HETM (300mg/kg; p.o.), TMLR (100mg/kg; p.o.), and ISQ (10mg/kg; p.o.), were compared with classical diuretics in 7days repeated-dose treatment. The urinary volume, sodium, potassium, chloride, bicarbonate, conductivity, pH and density were estimated in the sample collected for 15h. The plasmatic concentration of sodium, potassium, urea, creatinine, aldosterone, vasopressin, nitrite and angiotensin converting enzyme (ACE) activity were measured in samples collected at the end of the experiment (seventh day). Using pharmacological antagonists or inhibitors, we determine the involvement of bradykinin, prostaglandin and nitric oxide (NO) in ISQ-induced diuresis. In addition, reactive oxygen species (ROS) and the activity of erythrocytary carbonic anhydrase and renal Na(+)/K(+)/ATPase were evaluated in vitro.. HETM, TMLR and ISQ increased diuresis similarly to spironolactone and also presented K(+)-sparing effects. All groups presented both plasmatic aldosterone levels and ACE activity reduced. Previous treatment with HOE-140 (a B2-bradykinin receptor antagonist), or indomethacin (a cyclooxygenase inhibitor), or L-NAME (a NO synthase inhibitor), fully avoided the diuretic effect of ISQ. In addition, the 7days treatment with ISQ resulted in increased plasmatic levels of nitrite and reducing ROS production. Moreover, the renal Na(+)/K(+)/ATPase activity was significantly decreased by ISQ.. Our results suggest that the mechanisms through ISQ and extracts of Tropaeolum majus increase diuresis in SHR rats are mainly related to ACE inhibition, increased bioavailability of bradykinin, PGI2, and nitric oxide, besides an inhibitory effect on Na(+)/K(+)-ATPase.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Bradykinin; Disease Models, Animal; Diuresis; Diuretics; Epoprostenol; Ethanol; Hypertension; Male; Natriuresis; Nitric Oxide; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Quercetin; Rats; Rats, Inbred SHR; Signal Transduction; Sodium-Potassium-Exchanging ATPase; Solvents; Time Factors; Tropaeolum

Enzymatically modified isoquercitrin (EMIQ) is a water-soluble glycoside of quercetin produced from rutin by enzymatic treatment. We investigated the anti-hypertensive effect of orally administered EMIQ in spontaneously hypertensive rats (SHR). The systolic blood pressure (SBP) in SHR administered EMIQ at a dose of 3 and 26 mg/kg/d was significantly lower than that in the control group on d 22, 36 and 50 of administration. The effect of EMIQ (26 mg/kg/d) was higher than equimolar administration of quercetin. Diltiazem administered as a positive control also suppressed the increase in SBP. and the effect was stronger than that of EMIQ. In the control group, the mean values of mean blood pressure (MBP) and diastolic blood pressure (DBP) were increased after the start of administration. Although diltiazem suppressed the increase in MBP, no significant changes were observed in the EMIQ groups. Compared with the control group, EMIQ groups showed the incidental changes of MBP and heart rate on day 22 of administration only. These results indicate that EMIQ suppressed the increase in SBP in SHR dose-dependently, and was more effective than the aglycone quercetin. It was also speculated that EMIQ showed higher anti-hypertensive effect than quercetin due to the high bioavailability, and the mechanism of SBP suppression is possibly through the improvement of endothelial NO production. In conclusion, our results suggest that EMIQ shows possibility as a naturally-derived safe food material which has an antihypertensive effect.

Topics: Analysis of Variance; Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Diltiazem; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Rate; Hypertension; Male; Quercetin; Rats; Rats, Inbred SHR; Time Factors