Humans ; Neurodegenerative Diseases ; prevention & control ; Quercetin ; therapeutic use

OBJECTIVE: This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue. METHODS: A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis. RESULTS: Six potential active components, namely quercetin, β-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment. CONCLUSION Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.
Humans ; Quercetin/therapeutic use* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Drugs, Chinese Herbal ; Fatigue/drug therapy*

OBJECTIVETo observe the effect of quercetin on experimental spinal cord injury (SCI) in rats.

METHODSSixty Sprague-Dawley rats were randomly divided into four groups: Group A only for laminectomy, Group B for laminectomy with SCI, Group C for SCI and intraperitoneal injection with a bolus of 200 mg/kg quercetin and Group D for SCI and intraperitoneal injection of saline. SCI model was made by using modified Allen's method on T(12). Six rats of each group were killed at 4 h after injury and the levels of free iron and malondialdehyde (MDA) of the involved spinal cord segments were measured by bleomycin and thiobarbituric acid (TBA) assays separately. The recovery of hind limb function was assessed by Modified Tarlov's scale and inclined plane method at 7 d, 14 d and 21 d after SCI. The histological changes of the damaged spinal cord were also examined at 7 d after SCI.

RESULTSAfter SCI, the levels of free iron and MDA were significantly increased in Groups B and D, while not in Group C. The Modified Tarlov's score and the inclined plane angles were significantly decreased in Groups B, C and D. The histological findings were not improved.

CONCLUSIONSAfter SCI, quercetin can reduce the level of lipid peroxidation, but not improve recovery of function.

Animals ; Antioxidants ; therapeutic use ; Iron ; analysis ; Male ; Malondialdehyde ; analysis ; Quercetin ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; drug therapy ; metabolism ; pathology

OBJECTIVE: To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats. METHODS: Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE₂), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings. RESULTS: The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE₂ and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups. CONCLUSIONS LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE₂ biosynthesis.
Rats ; Animals ; Stomach Ulcer/pathology* ; Antioxidants/therapeutic use* ; Ranitidine/adverse effects* ; Aesculus ; Ulcer/drug therapy* ; Quercetin ; Plant Extracts/chemistry* ; Indomethacin/therapeutic use* ; Glutathione ; Superoxide Dismutase ; Rutin/adverse effects* ; Prostaglandins/adverse effects* ; Phytochemicals/therapeutic use*

OBJECTIVE: To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS). METHODS: Fourteen apolipoprotein E-deficient (ApoE^-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE^-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot. RESULTS: Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE^-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE^-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05). CONCLUSION Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.
Mice ; Animals ; Apelin ; Tissue Plasminogen Activator/metabolism* ; Quercetin/therapeutic use* ; AMP-Activated Protein Kinases/metabolism* ; Sirtuin 1/metabolism* ; Signal Transduction/physiology* ; Atherosclerosis/metabolism* ; Apolipoproteins E

OBJECTIVETo determine the efficacy of the plant-derived bioflavonoid, quercetin, for treating nonalcoholic fatty liver disease (NAFLD) by using a rat model, and to investigate the molecular mechanism underlying its therapeutic effects.

METHODSOne-hundred Sprague-Dawley rats were randomly assigned into the normal control group (normal group), untreated NAFLD model control group (model group), 75 mg/kg/day quercetin treatment group (low-dose group), and 300 mg/kg/day quercetin treatment group (high-dose group). The NAFLD rat model was established by providing four weeks of a high-fat diet; the normal group received normal rat chow diet. The quercetin treatments were administered for eight weeks after model establishment and control groups received simultaneous gavages of isotonic saline, with continuation of the respective diets. At the end of the eight weeks (experimental week 12), the rats were sacrificed for liver and serum collection. Intergroup differences in liver index, fasting blood glucose (FBG), triglycerides (TG), interleukin (IL)-18, IL-10, malondialdehyde (MDA), and histopathological features were assessed by independent samples t-test (normal vs. model), one-way ANOVA (model vs. treatments), and least significant difference t-test (pairwise comparisons); correlations were assessed by Pearson's correlation coefficient.

RESULTSCompared with the normal group, the model group showed significantly higher liver index (t=-2.327), FBG (t=-3.482), TG (t=-0.302), and serum IL-18 (t=-2.704) (all P less than 0.05), but significantly lower IL-10 (t=2.622, P less than 0.05); the MDA level was also higher in the model group, but the difference was not significant (t=-1.083, P less than 0.05). Livers from the model group showed obvious histological features of inflammation (lymphocyte and neutrophil infiltration) and steatosis (cytoplasmic lipid droplets). Inflammation was positively correlated with IL-18 (P less than 0.05), but negatively correlated with IL-10 (P less than 0.05), while steatosis was negatively correlated with IL-10 (P less than 0.05). Compared to the model group, quercetin treatment (both low- and high-dose) led to significant decreases in the liver index, FBG and IL-18 (all, P less than 0.01), and significant increase in IL-10 (P less than 0.05); however, the changes in liver index, FBG and IL-10 were not significantly different between the low- and high-dose treatment groups, but the high-dose of quercetin did induce a significantly greater decrease in IL-18 than the low-dose (P less than 0.05).

CONCLUSIONNAFLD rats have higher serum levels of IL-18 but lower levels of IL-10 than their healthy counterparts, and these differential cytokine expressions may be related to liver inflammation and steatosis. Quercetin treatment may help to delay the progression of NAFLD, possibly by adjusting the balance of inflammatory cytokines.

Animals ; Fatty Liver ; blood ; drug therapy ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Male ; Non-alcoholic Fatty Liver Disease ; Quercetin ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley

Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.
Antigens, CD/metabolism ; Antineoplastic Agents/*pharmacology/therapeutic use ; Carcinoma, Embryonal/*drug therapy/metabolism ; Cell Differentiation/*drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Flavonoids/*pharmacology/therapeutic use ; Gene Expression Regulation, Neoplastic ; Genistein/pharmacology/therapeutic use ; Humans ; Kaempferols/pharmacology/therapeutic use ; Models, Biological ; Phenols/*pharmacology/therapeutic use ; Quercetin/pharmacology/therapeutic use ; Resorcinols/pharmacology/therapeutic use ; Stilbenes/pharmacology/therapeutic use ; Symporters/metabolism ; Thyroid Neoplasms/*drug therapy/metabolism

AIM: To study the chemical constituents of Siegesbeckia pubescens. METHODS: The chemical constituents were isolated by extraction, crystallization and various chromatographic methods, and the chemical structures were elucidated on the basis of spectral analysis. In addition, the cytotoxic activity of compound 1 was evaluated using human lung cancer cell A 549. RESULTS: Four compounds were obtained, and their structures were identified as (E)-3-(3-oxobut-1-enyl)phenyl dimethylcarbamate (1), ent-2-oxo-15, 16, 19-trihydroxypimar-8(14)-ene (2), 16-acetylkirenol (3), 3, 7-dimethylquercetin (4). CONCLUSION Compound 1 is a new carbamate, and the IC(50) in MTT method of compound 1 was 58 μg·mL(-1).
Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; therapeutic use ; Asteraceae ; chemistry ; Carbamates ; isolation & purification ; pharmacology ; therapeutic use ; Cell Line, Tumor ; Humans ; Inhibitory Concentration 50 ; Lung Neoplasms ; drug therapy ; Molecular Structure ; Phytotherapy ; Plant Components, Aerial ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Quercetin ; analogs & derivatives ; isolation & purification

This study aims to investigate mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination(MT) in the treatment of bronchial asthma based on network pharmacology and in vivo experiment, which is expected to lay a theoretical basis for clinical application of the combination. First, the potential targets of MT in the treatment of bronchial asthma were predicted based on network pharmacology, and the "Chinese medicine-active component-target-pathway-disease" network was constructed, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the potential targets. Molecular docking was used to determine the binding activity of key candidate active components to hub genes. Ovalbumin(OVA, intraperitoneal injection for sensitization and nebulization for excitation) was used to induce bronchial asthma in rats. Rats were classified into control group(CON), model group(M), dexamethasone group(DEX, 0.075 mg·kg~(-1)), and MT(1∶1.5) group. Hematoxylin and eosin(HE), Masson, and periodic acid-Schiff(PAS) staining were performed to observe the effect of MT on pathological changes of lungs and trachea and goblet cell proliferation in asthma rats. The levels of transforming growth factor(TGF)-β1, interleukin(IL)6, and IL10 in rat serum were detected by enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein levels of mitogen-activated protein kinase 8(MAPK8), cyclin D1(CCND1), IL6, epidermal growth factor receptor(EGFR), phosphatidylinositol 3-kinase(PI3 K), and protein kinase B(Akt) by qRT-PCR and Western blot. Network pharmacology predicted that MAPK8, CCND1, IL6, and EGFR were the potential targets of MT in the treatment of asthma, which may be related to PI3 K/Akt signaling pathway. Quercetin and β-sitosterol in MT acted on a lot of targets related to asthma, and molecular docking results showed that quercetin and β-sitosterol had strong binding activity to MAPK, PI3 K, and Akt. In vivo experiment showed that MT could effectively alleviate the symptoms of OVA-induced asthma rats, improve the pathological changes of lung tissue, reduce the production of goblet cells, inhibit the inflammatory response of asthma rats, suppress the expression of MAPK8, CCND1, IL6, and EGFR, and regulate the PI3 K/Akt signaling pathway. Therefore, MT may relieve the symptoms and inhibit inflammation of asthma rats by regulating the PI3 K/Akt signaling pathway, and quercetin and β-sitosterol are the candidate active components.
Animals ; Asthma/drug therapy* ; Cyclin D1 ; Dexamethasone/adverse effects* ; Drug Combinations ; Drugs, Chinese Herbal/therapeutic use* ; Eosine Yellowish-(YS)/adverse effects* ; Ephedra ; ErbB Receptors ; Hematoxylin/therapeutic use* ; Interleukin-10 ; Interleukin-6 ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Molecular Docking Simulation ; Network Pharmacology ; Ovalbumin/adverse effects* ; Periodic Acid/adverse effects* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism* ; Quercetin ; RNA, Messenger ; Rats

OBJECTIVETo investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats.

METHODSThe quercetin (0.13 mmol/kg) was orally administrated in 50 min prior to hepatic ischemia-reperfusion injury. Ascorbic acid was also similarly administered. The hepatic content of quercetin was assayed by high performance liquid chromatography (HPLC). Plasma glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) activities and malondialdehyde (MDA) concentration were measured as markers of hepatic ischemia-reperfusion injury. Meanwhile, hepatic content of glutathione (GSH), activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO), total antioxidant capacity (TAOC), contents of reactive oxygen species (ROS) and MDA, DNA fragmentation were also determined.

RESULTSHepatic content of quercetin after intragastric administration of quercetin was increased significantly. The increases in plasma GPT, GOT activities and MDA concentration after hepatic ischemia-reperfusion injury were reduced significantly by pretreatment with quercetin. Hepatic content of GSH and activities of SOD, GSH-Px and TAOC were restored remarkably while the ROS and MDA contents were significantly diminished by quercetin pretreatment after ischemia-reperfusion injury. However, quercetin pretreatment did not reduce significantly hepatic XO activity and DNA fragmentation. Ascorbic acid pretreatment had also protective effects against hepatic ischemia-reperfusion injury by restoring hepatic content of GSH, TAOC and diminishing ROS and MDA formation and DNA fragmentation.

CONCLUSIONIt is indicated that quercetin can protect the liver against ischemia-reperfusion injury after oral pretreatment and the underlying mechanism is associated with improved hepatic antioxidant capacity.

Administration, Oral ; Animals ; Antioxidants ; pharmacokinetics ; therapeutic use ; Ascorbic Acid ; pharmacokinetics ; therapeutic use ; Biological Availability ; Biomarkers ; blood ; DNA Fragmentation ; Glutathione Peroxidase ; metabolism ; Liver ; blood supply ; drug effects ; enzymology ; Male ; Malondialdehyde ; blood ; Quercetin ; pharmacokinetics ; therapeutic use ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Reperfusion Injury ; blood ; enzymology ; metabolism ; prevention & control ; Superoxide Dismutase ; metabolism ; Transaminases ; blood ; Xanthine Oxidase ; metabolism