OBJECTIVETo investigate the effect of total flavone of haw leaves (TFHL) on the expression of nuclear factor erythroid-2 related factor (Nrf2) and other related factors in nonalcoholic steatohepatitis (NASH) rats induced by high-fat diet and then to further discuss the mechanism of TFHL's prevention against NASH.

METHODSHigh-fat diet was fed to 40 rats to establish the NASH model. Then model rats were intragastrically administrated with 40, 80, 160 mg/(kg•day) TFHL, respectively. The pathological changes of liver tissues in NASH rats were detected by oil red O and hematoxylin-eosin (HE) stainings. The expression of Nrf2 in rat liver was examined through immunohistochemistry. The level of 8-iso-prostaglandin F2α in serum was detected through enzyme linked immunosorbent assay (ELISA). The mRNA and protein levels of Nrf2 and other related factors in liver tissue were measured by real-time reverse transcriptionpolymerase chain reaction and western blot.

RESULTSLipid deposition, hepatic steatosis, focal necrosis in lobular inflammation and ballooning degeneration were emerged in livers of NASH rats. The 8-iso-prostaglandin F2α in the serum of NASH rats increased significantly compared with the control group (P<0.05). The mRNA of Nrf2, hemeoxyenase1 (HO-1) and the mRNA and protein levels of quinine oxidoreductase (NQO1) in NASH rats liver tissue showed a striking increase, while the mRNA levels of Keap1, r-glutamylcysteine synthethase (rGCS) and glutathione S-transferase (GST) were significantly decreased compared with the control group (P<0.05). After TFHL treatment, 8-iso-prostaglandin F2α level in serum significantly decreased, and Nrf2 mRNA and protein levels in hepatocytes nucleus enhanced compared with the model group (P<0.05 or 0.01). Meanwhile the Keap1 mRNA, the mRNA and protein levels of HO-1, NQO1 antibody, rGCS antibody, GST increased after TFHL treatment (P<0.05 or 0.01).

CONCLUSIONSNrf2 and other related factors were involved in development of NASH, and they also served as an important part in its occurrence. By regulating expression of Nrf2 and other related factors, TFHL may play a role in antioxidative stress and prevention of NASH.

Animals ; Cell Nucleus ; drug effects ; metabolism ; Crataegus ; chemistry ; Dinoprost ; metabolism ; Flavones ; pharmacology ; therapeutic use ; Lipids ; chemistry ; Liver ; drug effects ; metabolism ; pathology ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Non-alcoholic Fatty Liver Disease ; drug therapy ; genetics ; pathology ; Phytotherapy ; Plant Leaves ; chemistry ; RNA, Messenger ; genetics ; metabolism ; Rats, Sprague-Dawley

The objective of this study was to investigate factors that influence the success of resynchronization protocols for bovines with and without progesterone supplementation. Cow synchronized and not found pregnant were randomly assigned to two resynchronization protocols: ovsynch without progesterone (P4) supplementation (n = 66) or with exogenous P4 administered from Days 0 to 7 (n = 67). Progesterone levels were measured on Days 0 and 7 of these protocols as well as 4 and 5 days post-insemination. Progesterone supplementation raised the P4 levels on Day 7 (p < 0.05), but had no overall effect on resynchronization rates (RRs) or pregnancy per artificial insemination (P/AI). However, cows with Body Condition Score (BCS) > 3.5 had increased P/AI values while cows with BCS < 2.75 had decreased P/AI rates after P4 supplementation. Primiparous cows had higher P4 values on Day 7 than pluriparous animals (p = 0.04) and tended to have higher RRs (p = 0.06). Results of this study indicate that progesterone supplementation in resynchronization protocols has minimal effects on outcomes. Parity had an effect on the levels of circulating progesterone at initiation of the protocol, which in turn influenced the RR.
Animals ; Cattle/*physiology ; Dinoprost/administration & dosage/*pharmacology ; Estrus Synchronization/*drug effects/methods ; Female ; Fertility Agents/administration & dosage/pharmacology ; Gonadotropin-Releasing Hormone/administration & dosage/*pharmacology ; Insemination, Artificial/veterinary ; Ovulation/drug effects ; Pregnancy ; Progesterone/administration & dosage/*pharmacology ; Tromethamine/administration & dosage/*pharmacology

OBJECTIVETo investigate the effect of chloroquine on airway hyperresponsiveness in asthmatic mice and explore the possible mechanism.

METHODSBalb/c mouse models of asthma established using OVA received intraperitoneal injections of chloroquine, dexamethasone, or both prior to OVA challenge. Within 24 h after the final challenge, airway hyper- responsiveness (AHR) of the mice was assessed, and the total cell count and the counts of different cell populations in the bronchoalveolar lavage fluid (BALF) were determined under light microscopy. The severity of lung inflammation was evaluated using HE staining, and the concentrations of IL-6 and PGF2α in the BALF were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSChloroquine pretreatment significantly decreased AHR (P<0.001) in the asthmatic mice and reduced the total cell count (P<0.01), eosinophils (P<0.001), neutrophils (P<0.01), and PGF2α levels in the BALF. Chloroquine combined with low-dose dexamethasone significantly lessened inflammations around the bronchioles (P<0.05) and blood vessels (P<0.01) in the lung tissue, and obviously lowered IL-6 (P<0.05) and PGF2α (P<0.001) in the BALF in the asthmatic mice.

CONCLUSIONChloroquine can inhibit AHR in asthmatic mice and produce better anti-inflammatory effect when combined with dexamethasone for treatment of neutrophilic asthma.

Animals ; Asthma ; chemically induced ; drug therapy ; Bronchoalveolar Lavage Fluid ; cytology ; Chloroquine ; pharmacology ; Dexamethasone ; pharmacology ; Dinoprost ; metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; cytology ; Inflammation ; pathology ; Interleukin-6 ; metabolism ; Leukocyte Count ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; Neutrophils ; cytology

OBJECTIVETo observe the clinical significance of nitric oxide (NO) and 8-isoprostane (8-isoPG) changes in exhaled breath condensate ( EBC) of acute respiratory distress syndrome (ARDS) patients after treated by Qingfei Decoction (QD).

METHODSTotally 48 ARDS patients receiving mechanical ventilation were equally assigned to the QD treatment group and the control group by random digit table. EBC specimens were collected by modified Ecoscreen breath condensate collector (German JAEGER Company) on the first day and the fifth day after confirmed diagnosis of ARDS. Concentrations of NO and 8-isoPG in EBC were measured by ELISA. The oxygenation index and APACHE II scores were recorded at the same time.

RESULTS(1) The fatality rate in the QD treatment group was lower than that in the control group (8.3% vs 37.5%, P < 0.05). (2) After treatment NO and 8-isoPG concentrations in EBC were lower in the QD treatment group (34.49 ± 5.67 µmol/L, 30.09 ± 7.89 ng/L) than in the control group (39.78 ± 9.27 µmol/L, 35.65 ± 8.90 ng/L; P < 0.05). (3) After treatment improved oxygenation index value was higher in the QD treatment group than in the control group (120.88 ± 35.16 vs 101.50 ± 37.70, P < 0.05). After treatment APACHEII scores was lower in the QD treatment group than in the control group (6.21 ± 3.51 vs 10. 26 ± 4.33, P < 0.05).

CONCLUSIONTreatment of ARDS patients by QD was favorable in controlling inflammation, alleviating lung injury, and improving clinical efficacy.

Breath Tests ; Dinoprost ; analogs & derivatives ; analysis ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Inflammation ; Nitric Oxide ; analysis ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; drug therapy

The aim of the present study was to evaluate the protective effect of catalpol on vascular endothelial function in STZ-induced type 2 diabetes mellitus (T2DM) rats. 40 high-fat diet with STZ-induced diabetes rats were randomly divided into model group, catalpol low-dose, middle-dose and high-dose group (10, 50, 100 mg x kg(-1) x d(-1)), 10 normal Wistar rats were used as the normal group. The normal and model groups were given an equivalent amount of saline. All reagents were administered by oral gavage for 6 weeks. After 6 weeks, blood glucose and lipids were detected by an automatic biochemical analyzer. The endothelium-dependent vasodilation response of thoracic aortar was detected. The pathological changes of the thoracic aorta were observed by HE staining. Ser- um nitric oxide (NO), 8-iso prostaglandin F2α (8-iso-PGF2α) and superoxide dismutase (SOD) were detected by ELISA. Reactive oxygen species (ROS) level of thoracic aorta was detected by fluorescence method. The expression of Nox4 and p22phox mRNA and protein in aortic tissue were detected by RT-PCR and Western-blot respectively. After catalpol treatment, endothelial damage of thoracic aorta was attenuated significantly; ROS level of thoracic aorta and serum level of 8-iso-PGF2α were decreased significantly; serum NO and SOD levels were remarkably elevated; expression of Nox4, p22phox mRNA and protein in thoracic aorta were significantly reduced (P < 0.05). Therefore, catalpol has protective effect on endothelial of T2DM, its mechanism may be associated with the down-regulation of Nox4 and p22phox expression, inhibiting oxidative stress reaction response.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; pathology ; Diabetes Mellitus, Type 2 ; pathology ; Dinoprost ; analogs & derivatives ; metabolism ; Endothelium, Vascular ; drug effects ; metabolism ; pathology ; Enzyme Inhibitors ; pharmacology ; Gene Expression Regulation ; drug effects ; Iridoid Glucosides ; pharmacology ; Male ; NADPH Oxidase 4 ; NADPH Oxidases ; antagonists & inhibitors ; genetics ; metabolism ; Nitric Oxide ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism

Blood Glucose ; metabolism ; Diabetes Complications ; prevention & control ; Diabetes Mellitus, Type 1 ; blood ; metabolism ; physiopathology ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; physiopathology ; Dinoprost ; analogs & derivatives ; blood ; Glucose ; metabolism ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents ; pharmacology ; Insulin ; pharmacology ; Oxidative Stress

The objective of this study was to investigate the effects of oxytocin infusion on corpus luteum (CL) function during early to mid-diestrus by measuring luteal size (LS) and luteal blood flow (LBF) along with plasma levels of progesterone (P4) and prostaglandin metabolites (13,14-dihydro-15-keto-prostaglandin F2alpha, PGFM). On day (D) 7 of the estrus cycle (D1 = ovulation), seven cows received 100 IU of oxytocin (OXY) or placebo (PL) following a Latin square design. LS and LBF increased in both groups over time and no differences were observed between the groups. PGFM did not differ either within the groups over time or between the groups at any time point. P4 of the OXY group was higher compared to that of the the PL group 360 min after the infusion (p = 0.01) and tended to be higher at the time points 450 min, 48 h, and 72 h (all p = 0.08). Results from this study support the hypothesis that OXY is not directly involved in the mechanism(s) governing blood flow of the CL and has no remarkable effects either on luteal size or P4 and PGFM plasma levels. Further investigation is needed to elucidate the role of OXY in CL blood flow during early and late luteal phases.
Animals ; Cattle/*physiology ; Corpus Luteum/blood supply/*drug effects/secretion/ultrasonography ; Dinoprost/analogs & derivatives/blood ; Estrous Cycle/*drug effects/physiology ; Female ; Immunoenzyme Techniques/veterinary ; Organ Size/physiology ; Oxytocin/*pharmacology ; Progesterone/blood/*secretion ; Random Allocation ; Ultrasonography, Doppler, Color/veterinary

OBJECTIVETo compare the anti-inflammatory effect of Radix Paeoniae Rubra and Radix Paeoniae Alba by animal experiment and metabolimic analysis.

METHODTo establish the rats model of toes swelling caused by carrageenan, study the anti-inflammatory effect of Radix Paeoniae Rubra and Radix Paeoniae Alba. The serum samples were analyzed by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), to find out the potential identification biomarker by PLS-DA.

RESULTBoth of the extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba have good effects of inhibition to swelling caused by carrageenan in 0.5-1 h, and the extract of Radix Paeoniae Rubra also show significant inhibition in 2-3 h. Glutathione( GSH), gamma-aminobutyric acid (GABA), prostaglandin F2alpha (PGF2alpha), prostaglandinE3 (PGE3), leukotrieneA4 (LTA4), prostaglandinE2 ( PGE2) are proven to be significant expressed biomarkers. Radix Paeoniae Rubra and Radix Paeoniae Alba may have great influence on PGF2alpha and PGE3. There was also significant difference between the effects of Radix Paeoniae Rubra and Radix Paeoniae Alba, which suggested the difference of anti-inflammatory between the two herbs.

CONCLUSIONThe results of metabolomics are related with the results of classic pharmaco- experiment, which is helpful for the further research of the mechanism of action of Radix Paeoniae Rubra and Radix Paeoniae Alba.

Alprostadil ; analogs & derivatives ; blood ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Chromatography, Liquid ; methods ; Dinoprost ; blood ; Male ; Metabolomics ; Paeonia ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; methods

To observe the effects of simvastatin on plasma superoxide dismutase (SOD), malonaldehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) as well as uric acid (UA) and serum lipids in patients with stable angina. METHODS Eighty-five patients with stable angina were divided into 4 groups, including hyperlipemia treatment group (HLT), hyperlipemia control group (HLC), normolipemia treatment group (NLT), and normolipemia control group (NLC). All the patients received routine treatment according to the guideline of CHD treatment, and those in the treatment groups were given Simvastatin (40 mg) every night, whereas those in the control group received placebo for 3 months. Before and after the treatments, the levels of plasma 8-iso-PGF2α were measured by enzyme-linked immunosorbent assay, and the plasma levels of SOD and MDA were detected by colorimetric method. LDL, HDL, TC, TG, and UA were also measured biochemically. RESULTS Compared with the control group, both of the treatment groups showed significantly increased levels of SOD and decreased MDA, 8-iso-PGF2α, UA and plasma lipids after the treatments (P<0.05). CONCLUSION In patients with coronary heart disease, simvastatins can decrease plasma lipids, inhibit lipid peroxidations, and promote the clearance of free radicals, thereby alleviating the oxidative stress.
Aged ; Angina Pectoris ; blood ; drug therapy ; Dinoprost ; analogs & derivatives ; blood ; Female ; Humans ; Male ; Malondialdehyde ; blood ; Middle Aged ; Simvastatin ; pharmacology ; therapeutic use ; Superoxide Dismutase ; blood

OBJECTIVETo explore the acute effects of testosterone at the physiological level on PGF2alpha-induced increase in intracellular Ca2+ in cultured vascular smooth muscle cells (VSMCs).

METHODSVSMCs from the thoracic aorta of male Sprague-Dawley rats were cultured using the explant method. The subconfluent VSMCs were incubated with serum-free medium for 24 hours to obtain quiescent non-dividing cells and then treated with the indicated agents. For the measurement of [Ca2+]i, the VSMCs were loaded with fura-2. Changes of [Ca2+]i were determined ratiometrically with a Nikon TE-2000E system.

RESULTSThe resting level of [Ca2+]i was around 100 nmol/L in the VSMCs. Exposing cells to perfusate containing 10 micromol/L PGF2alpha triggered an immediate and transient peak in [Ca2+]i, which gradually decreased afterwards. Interference at the peak with the physiological concentration (40 nmol/L) of testosterone significantly decreased the peak-to-baseline time of [Ca2+]i, compared with ethanol vehicle (104.9 +/- 27.0 s vs 153.5 +/- 40.4 s, P < 0.01). Pretreatment with testosterone at 40 nmol/L for 2 minutes also reduced the peak-to-baseline time of [Ca2+]i significantly in comparison with the ethanol control (120.6 +/- 32.0 s vs 151.4 +/- 27.4 s, P < 0.01), but it had no significant effect on the peak level of PGF2alpha-induced intracellular Ca2+ (390.0 +/- 126.0 nmol/L vs 403.4 +/- 160.7 nmol/L, P > 0.05).

CONCLUSIONTestosterone at physiological concentration inhibits PGF2alpha-induced Ca2+ fluxes, probably via receptor-operated calcium channels by a non-genomic mechanism in VSMCs, which may be involved in the vasodilatory effect of testosterone.

Animals ; Calcium ; metabolism ; Cells, Cultured ; Dinoprost ; pharmacology ; Male ; Muscle, Smooth, Vascular ; cytology ; drug effects ; Myocytes, Smooth Muscle ; metabolism ; Rats ; Rats, Sprague-Dawley ; Testosterone ; metabolism ; physiology