Aurantii Fructus is the dried and immature fruit of Citrus aurantium and its cultivars. To investigate the chemical constituents of Aurantii Fructus, the separation and purification of constituents were performed by column chromatography on silica gel LH-20, HW-40, ODS, PHPLC and PTLC. Fourteen flavonoids, including four flavone glycosides and ten polymethoxyflavones (PMFs) were isolated from the EtOAc fraction and Petroleum ether fraction of Aurantii Fructus and their structures were identified by physicochemical properties and spectral data (NMR and MS) as (2R) -and (2S)-6"-O-acetylprunin (1,2), naringenin-7-O-β-D-glucopyranside (3), 5,7,4'-trihydroxy-8,3'-dimethoxyflavone-3-O-6"-(3-hydroxyl-3-methylglutaroyl)-β-D-glucopyranoside(4), 4'-hydroxy-5,6, 7-trimethoxyflavone (5), natsudaidain (6), nobiletin (7), sinensetin (8), 5,6,7,4'-tetramethoxyflavone (9), 5,7,8,4'-tetramethoxyflavone (10), 3,5,6,7,8,3',4'-heptamethoxyflavone (11), tangeretin (12), 5-demethyl nobiletin (13), and 5-hydroxy-6,7,3', 4'-tetramethoxyflavone (14). Compound 3-5 s were isolated from this plant for the first time and compound 1 was a new one.
Citrus ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Flavonoids ; chemistry ; isolation & purification ; Fruit ; chemistry ; Mass Spectrometry ; Molecular Structure

To establish a method for the determination of cucurbitacin in plasma samples, in order to study the in vivo pharmacokinetic characteristics of cucurbitacin in rats. Rats were intravenously injected with cucurbitacin. With diphenhydramine as the internal standard (IS), the plasma concentrations of cucurbitacin in rat plasma at different time points were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). With electrospray ionization source, the positive ion detection in the multiple reaction monitoring mode was conducted to determine the ion-pairs for target compound and IS were m/z 503.2/113.1 and m/z 256.0/167.2, respectively. Agilent ZOBAX SB-C18 column (2.1 mm x 50 mm, 1.8 microm) was adopted and eluted with methanol and 0.1% formic acid (55:45), and the flow rate was 0.2 mL x min(-1). DAS 2.0 software was applied to fit the blood concentration and calculate corresponding pharmacokinetic parameters. The rats were intravenously injected with cucurbitacin at the concentration of 3.0 mg x kg(-1). The target blood quality concentration show good linear relations within the range of 10.5-3 150 microg x L(-1) (R2 = 0.996), the lower limit of the standard curve was 10.5 microg x L(-1), and the signal to noise ratio S/N = 12. Intra- and inter-day precisions RSD was less than 6.9% and 14%, respectively; The accuracy RE ranged between 0.20% and 3.7%; The extraction recoveries ranged between 92.7% and 97.1%. Regarding the pharmacokinetic parameters of tail intravenous injection of cucurbitacin, AUC (0-t) was (811.615 +/- 111.578) microg x h x L(-1), (t1/2) was (1.285 +/- 1.390) h, CL was (3.627 +/- 0.487) L x h x kg(-1), and V(d) was (6.721 +/- 7.429) L x kg(-1). In this study, researchers established a simple, accurate, sensitive and highly specific method for determining the blood concentration of cucurbitacin, and reported the in vivo pharmacokinetic characteristics of cucurbitacin in rats for the first time.
Administration, Oral ; Animals ; Cucurbitaceae ; chemistry ; Cucurbitacins ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Male ; Rats ; Rats, Wistar

OBJECTIVETo explore the effect of Yixintai Granule (YG) on mRNA and protein expression levels of AQP2 in renal medulla of chronic heart failure (CHF) rabbits.

METHODSCHF rat model was established by ear marginal vein injection of adriamycin. Successfully modeled rabbits were divided into the model group, the high (8.4 g/kg), middle (4.2 g/kg), and low dose (2.1 g/kg) YG group, and the Furosemide group (2 mg/kg). Besides, a normal control group was set up. Equal volume of physiological saline was administered to rabbits of the model group and the normal control group by gastrogavage. YG at different doses was administered to rabbits of the 3 YG groups by gastrogavage. The intervention lasted for 4 weeks, once per day. After treatment the urine volume and pathomorphological changes of renal medulla tissue were observed. mRNA and its protein expression levels of AQP2 were detected.

RESULTSCompared with the normal control group, the urine volume decreased significantly, mRNA and protein expression levels of renal medulla AQP2 increased significantly in the model group (all P < 0.01). Compared with the model group, the urine volume increased significantly, and mRNA and protein expression levels of renal medulla AQP2 decreased significantly in all medicated groups (all P < 0.01). Compared with the low dose YG group, the urine volume significantly increased and the mRNA expression level of renal medulla AQP2 significantly decreased in the middle and high dose YG groups (all P < 0.01). The expression level of AQP2 protein significantly decreased in the high dose YG group (P < 0.01). Pathological changes of the renal medulla was the most obviously seen in the model group. But they were alleviated to various degrees in all medicated groups. They were more obviously attenuated in the middle and high dose YG groups.

CONCLUSIONYG could improve CHF possibly through down-regulating mRNA and protein expression levels of AQP2 in renal medulla, and elevating the urine volume.

Animals ; Aquaporin 2 ; genetics ; metabolism ; Chronic Disease ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Heart Failure ; drug therapy ; metabolism ; RNA, Messenger ; metabolism ; Rabbits ; Rats, Sprague-Dawley

One hundred and forty six elderly patients with constipation undergoing colonoscopy during March 2012 and August 2013 were randomly assigned to trial and control groups.Seventy patients in trial group received Macrogol electrolytes powder combined with Chinese herb medicine Simo decoction for bowel preparation and 76 patients in control group received macrogol electrolytes powder only.The first defecation,times of defecation and tolerance of patients were compared between two groups.The quality of bowel preparation was evaluated by endoscopists with Boston Bowel Preparation Scale (BBPS).The first defecation time was shorter in trial group than that in control group (55.7 ± 27.9 vs.72.9 ± 34.8,P ＜ 0.05).However,no statistical significance was found in the times of defecation and tolerance of patients between two groups.The mean BBPS score in trial groups was higher than that in control group (7.87 ± 1.08 vs.6.97 ± 0.96,P ＜ 0.05).Chinese herb medicine Simo decoction combined with conventional method shows satisfactory result for bowel preparation in elderly patients with constipation undergoing colonoscopy.

To compare the pharmacokinetics of syringin, eleutheroside E and isofraxidin after intravenous administration of each monomer and Ciwujia injection. Twenty-four Sprague-Dawley rats were randomly divided into four groups and intravenously administrated with syringin, eleutheroside E, isofraxidin, and Ciwujia injection, respectively. The concentrations of the three components in rat plasma were determined by LC-MS/MS. DAS 2.0 software was applied to calculate the pharmacokinetic parameters while the SPSS 17.0 software was used for statistical analysis. Significant difference (P < 0.05) was found between each monomer and the injection on the main pharmacokinetic parameters such as AUC, CL and t1,/2. Compared with the injection, the group treated with the syringin has obvious decrease in AUC, and increase in CL while the group treated with eleutheroside E has obvious increase in AUC, and decrease in CL The t1/2 of isofraxidin was prolonged in Ciwujia injection. Pharmacokinetic characters of the ingredients in the injection varied greatly from the monomer. Other constituents in the injection may have an impact on the pharmacokinetic profiles of these three components.
Administration, Intravenous ; Animals ; Coumarins ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Lignans ; administration & dosage ; blood ; pharmacokinetics ; Male ; Phenylpropionates ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the clinical effect of combined treatment with safflor yellow powder injection and benazepril in treating patients with diabetic nephropathy (DN).

METHODSSeventy-six patients with DN were randomly assigned to the treatment group (39 cases) and the control group (37 cases). Conventional treatment for lowering blood glucose was given to both groups, but to the control group 10 mg benazepril was given orally once a day additionally, while to those in the treatment group the same dosage of benazepril po. and 150 mg/d of safflor yellow powder injection by adding in 250 mL 0.9% normal saline for intravenous dripping. The therapeutic course for them all was 15 days, and all patients received two courses with an interval of 5 days. Changes of clinical symptoms, urinary albumin excretion rate (UAER), blood and urinary levels of beta2 -microglobulin (beta2 -MG), urinary level of alpha1-microglobulin (alpha1 -MG), D-dimer (D-D) and plasma fibrinogen (FIB) were observed.

RESULTSThe total effective rate in the treatment group was higher than that in the control group (84.62% vs 59.45 %, P < 0.05). The total score of syndrome in the treatment group was lower than that in the control group (P < 0.05). Levels of UAER, 132-MG in serum and in urine, alpha1-MG in urine were decreased significantly after after 2 courses of treatment in both groups, showing significant difference as compared with before treatment (P < 0.05 or P <0.01), and the decrements were more significant in the treatment group than those in the control group (P <0.05); while decrease of FIB, D-D only happened in the treatment group (P <0.01), so the post-treatment data in the treatment group were significantly lower as compared with those in the control group (P <0.01).

CONCLUSIONCombined therapy with safflor yellow injection and benazepril is superior to benazepril alone in reducing urinary albumin, improving renal function and blood hyperviscosity manner for patients with DN, suggesting the combination of the two could play their respective superiorities and act in cooperation for retarding the progression of DN.

Adult ; Albumins ; analysis ; Benzazepines ; administration & dosage ; Blood Glucose ; Diabetic Nephropathies ; drug therapy ; metabolism ; urine ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Kidney Function Tests ; Male ; Middle Aged

OBJECTIVE: To observe the chemical groups changing in rat kidney with regard to fatal hyperthermia by Fourier transform infrared microspectroscopy (FTIR-MSP) and to provide a new method to diagnose fatal hyperthermia. METHODS: Rats were sacrificed by hyperthermia, brainstem injury, massive hemorrhage and asphyxiation and divided into groups. The renal samples were dissected immediately after death. The data of infrared spectroscopy in glomerulus were measured by FTIR-MSP. RESULTS: The absorbances of 3290, 3070, 2850, 1540 and 1396 cm(-1) significantly increased (P < 0.05), and the ratios of Al650/A3290 and A1650/A1540 significantly decreased (P < 0.05) in group of hyperthermia. CONCLUSION FTIR-MSP can analyze the changes of chemical groups of kidney as an auxiliary diagnosis for discriminating hyperthermia with other causes of death.
Animals ; Fever/mortality* ; Fourier Analysis ; Kidney/metabolism* ; Microspectrophotometry ; Rats ; Spectroscopy, Fourier Transform Infrared/methods*

Objective To evaluate the feasibility of 3-(4-~(18)F-fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno [3,4-c]pyridin-5-one ( is F-FDTP) as a potential dopamine D4 receptor PET imaging agent.Methods ~(18)F-FDTP solution in ethanol-physiological saline was incubated with calf serum to test its in vitro stability through the determination of radiochemical purity.Normal rats were injected intravenously with ~(18)F-FDTP and then sacrificed at 2,5,10,15,30,60 and 120 min after anesthesia.Blood,organs and brain tissue samples were collected.All samples were weighed and measured for radioactivity.The uptake of samples was expressed as percentage activity of injection dose per gram of tissue ( % ID/g).Results The stability of ~(18)F-FDTP was satisfactory and its radiochemical purity was above 95% after incubation 120 min at 37℃ in calf serum.The biodistribution showed that ~(18)F-FDTP could penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal certex,hippocampus,cerebellum,where the D_4 receptor was reportedly located.The radioactivities in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum,pons were (0.42±0.03),(0.46±0.05),(0.54±0.04),(0.39±0.04),(0.45±0.06),(0.35±0.04) %ID/g,respectively,2 min post injection.And there was difference between the normal biodistribution results and the blocking experimental results:(0.36 ±0.05),( 0.33±0.05 ),(0.55±0.05 ),(0.30±0.07 ),(0.34±0.07 ) and (0.32±0.04) % ID/g in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum and pons,respectively.Conclusions ~(18)F-FDTP can penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal cortex,hippocampus,cerebellum,where the D_4 receptor was known to concentrate.These preliminary results suggest that ~(18)F-FDTP is a potential dopamine D_4 receptor imaging agent and further studies are needed.

OBJECTIVE: To investigate and analyze the changes of postmortem human biochemical indexes. METHODS: Subclavian venous blood samples were collected from 81 cases of traffic fatalities. Thirteen blood biochemical indexes including liver function (ALT, AST, TBIL and DBIL), renal function (UA and Cr), cardiac function (CK, CK-MB and LDH), electrolytes (K+, Na+ and Cl-), and glucose (GLU) were tested by Roche cobas c311 automatic biochemical analyzer. The descriptive analysis was made by SPSS 17.0 statistical software. RESULTS: The values of ALT, AST, CK, CK-MB, LDH and K+ were higher than normal reference values with more fluctuations. The values of TBIL, DBIL, UA, Cr, Na+, Cl- and GLU were relatively stable with less fluctuations. CONCLUSION The postmortem human blood biochemical indexes of liver function, renal function, cardiac function, electrolytes and glucose could be affected by the factors, especially hemolysis and autolysis. The biochemical indexes, particularly enzymes, increased significantly with higher standard deviation.
Accidents, Traffic/mortality* ; Autopsy ; Blood Chemical Analysis/methods* ; Heart Function Tests ; Humans ; Kidney Function Tests ; Liver Function Tests ; Reference Values

OBJECTIVE: To explore the changes and rules of biochemical markers in serum of guinea pigs after death caused by hypothermia and to provide references for fatal hypothermia diagnosis by serum biochemical markers. METHODS: Twenty guinea pigs were randomly divided into experimental group and control group. The guinea pigs in the experimental group were kept at -30 °C until death, while the ones in control group were decapitated after same survival intervals at 25 °C. The serum was extracted from the whole blood of right ventricular immediately. Subsequently, a series of serum biochemical markers were analyzed by auto bio-chemical analyzer. RESULTS: The levels of glucose, uric acid, creatinine and urea nitrogen in the experimental group were significantly higher than those in control group, respectively (P<0.05). Compared with the control group, the levels of total protein and albumin were significantly lower in the experimental group (P<0.05). There were no significantly differences of the levels of other markers such as serum enzymes and ions observed between the two groups. CONCLUSION There are characteristic changes of some specific serum biochemical markers in fatal hypothermia, which may be potentially useful for auxiliary diagnosis of fatal hypothermia.
Animals ; Biomarkers/blood* ; Cause of Death ; Guinea Pigs ; Hypothermia