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1.
The effects were investigated of a partially purified subfraction (FS-1) isolated from Delphinium denudatum on sustained repetitive firing (SRF) of cultured neonatal rat hippocampal pyramidal neurons. The blockade of sustained repetitive firing is one of the basic mechanisms of antiepileptic drugs at the cellular level. Using the whole cell current-clamp technique, sustained repetitive firing was elicited in pyramidal neurons under study by a depolarizing pulse of 500 ms duration, 0.3 Hz and 0.1-0.6 nA current strength. FS-1 (0.01-0.06 mg/mL) reduced the number of action potentials per pulse in a dose-dependent manner until no action potentials were elicited for the remainder of the pulse. There was a corresponding use-dependent reduction in amplitude and Vmax of action potentials. The Vmax of action potential 1 exhibited a dose-dependent reduction. At a dose of 0.06 mg/mL FS-1 reduced Vmax to 29%-38% and amplitude to 16%-20 % of the control values. The blockade of sustained repetitive firing by FS-1 was reversed by hyperpolarization of the membrane potential (-65 to -75 mV) while depolarization of the membrane potential (-53 mV to -48 mV) potentiated the block. The results suggest that FS-1 blocks sustained repetitive firing in hippocampal neurons in a use-dependent and voltage-dependent manner similar to the prototype anticonvulsant drug, phenytoin. However, unlike phenytoin, which binds preferably to the inactive state, the compounds present in FS-1 also interacted with the resting state of the Na+ channels by reducing Vmax of action potential 1. The results indicate that the partially purified FS-1 subfraction of Delphinium denudatum contains a potent anticonvulsant compound.  相似文献   

2.
An investigation was designed and conducted to compare the pharmacokinetics difference of paeoniflorin after oral administration of the extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba to rats on separate occasions. Quantification of paeoniflorin in rat plasma was achieved using a simple and rapid HPLC method for pharmacokinetic study. After oral administration of decoctions of Radix Paeoniae Rubra and Radix Paeoniae Alba, paeoniflorin was absorbed and reached a maximum concentration of 3.69 ± 1.46 and 1.46 ± 0.29 (p < 0.05) μg/ml at 1.67 ± 0.43 and 0.80 ± 0.35 h (p < 0.05), respectively. Compared to the AUC (18.85 ± 7.54 μg h/ml) after oral administration of the paeoniflorin solution, a smaller AUC (10.61 ± 1.51 μg h/ml, p < 0.05) and a larger AUC (24.89 ± 7.41 μg h/ml) of paeoniflorin after oral administration of the decoctions of Radix Paeoniae Alba and Radix Paeoniae Rubra were obtained, respectively. There were statistically significant differences in pharmacokinetic parameters of paeoniflorin including the tmax, Cmax, AUC, t1/2, CL, and Vd among the animals orally administered the decoctions of Radix Paeoniae Rubra and Radix Paeoniae Alba. In particular, the parameters of tmax, Cmax, and AUC of paeoniflorin were remarkably increased (P < 0.05, P < 0.001) when oral administering paeoniflorin in the decoctions of Radix Paeoniae Rubra, but t1/2, Vd, and CL were decreased (P < 0.05 or P < 0.01), in comparison of the decoction of Radix Paeoniae Alba.  相似文献   

3.
??OBJECTIVE To investigate the pharmacokinetics of matrine injection by different routes of administration. METHODS Twenty healthy SD rats were enrolled in this study. They were randomly divided into two groups and received intraperitoneal and intravenous administration of matrine injection at dose of 15 mg??kg-1 respectively. Blood samples (0.3-0.4 mL) were immediately collected into heparinized tubes before injection and at 0.033, 0.083, 0.167, 0.333, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 h after injection. Plasma sample concentrations were determined by a validated LC-MS/MS method. The pharmacokinetic parameters including AUC0-12, AUC0-??, MRT0-12, MRT0-??, t1/2, Vd, CL and ??max were calculated. RESULTS The main pharmacokinetic parameters for matrine after intraperitoneal and intravenous administration at dose of 15 mg??kg-1 were as follows:AUC0-12 (10 166??2 426), (12 217??2 968) ng??mL-1??h;AUC0-?? (10 230??2 432), (12 300??3 031)- ng??mL-1??h;MRT0-12 (1.91??0.41), (2.14??0.54) h;MRT0-?? (2.01??0.41), (2.26??0.64) h; t1/2(2.26??0.89), (2.60??1.25) h;Vd(4 998??2 010), (6 175??2 540) mL;CL (1 531??315.0), (1 727??475.6) mL??h-1??kg-1; ??max (5 246??1 187), (8 503??1 101) ng??mL-1, respectively. The bioavailability of intraperitoneal administration is 83.21%. CONCLUSION No significant differences were observed in AUC, MRT, t1/2 and CL values of matrine between different administrations except for ??max and Vd.  相似文献   

4.
We previously reported on the significant dose-dependent diuretic effects produced in laboratory rats by hot water infusions and methanol extracts of Withania aristata Ait., where notable increases were observed in the excretion of water and sodium, with an interesting potassium-saving effect. The present study gives the results of the diuretic effects in rats of the hexane, dichloromethane, ethyl acetate, butanol and methanol–water fractions of the previously studied methanol extract.

Water excretion rate, pH, density, conductivity and content of Na+, K+ and Cl were measured in the urine of the rats when subjected to hypersaline conditions. Of the above fractions, the methanol:water extract (100 mg/kg) showed the most interesting diuretic activity (25%; **p < 0.01), which suggested that increase in the polarity of the extracting solvent led to an increase in the concentration of the polar compounds responsible for the diuretic effect. These data, together with previous results on the aqueous and methanol extracts, reaffirm assertions made regarding the effectiveness of the extracts of this plant against urinary pathologies in the Canary Islands folk medicine.  相似文献   


5.
??OBJECTIVE To study the enzymatic kinetics of TM-2 in rat, Beagle dog and human liver microsomes by LC-MS/MS. METHODS TM-2 was incubated with liver microsomal incubation system. LC-MS/MS method was established for quantitative analysis of TM-2 with cabazitaxel as internal standard. The enzyme kinetics parameters Vmax and Km was calculated by the GraphPad Prism 5.0 software. RESULTS A rapid and sensitive LC-MS/MS method was developed to study the enzyme kinetics of TM-2 in rat, Beagle dog and human liver microsome. The corresponding enzymatic kinetic parameters in rat, Beagle dog and human were as follows: Vmaxvalues were 16.3, 354.6 and 154.8 nmol??min-1??mg(protein)-1, respectively; Km values were 25.7, 313.8 and 89.4 ??mol??L-1, respectively; CLint values were 0.63, 1.13 and 1.73 mL??min-1??mg(protein)-1, respectively. CONCLUSION The result indicates that there are species differences in the activity of metabolic enzyme and the affinity of TM-2 to the metabolic enzyme. Enzyme kinetic parameters obtained of TM-2 provide important parameters for the further study.  相似文献   

6.
??OBJECTIVE To characterize the metabolism of genistin and study its enzymatic kinetics in rat liver microsome by HPLC-MS. METHODS Genistin was incubated with rat liver microsomal incubation system. HPLC-MS method was used to characterize the metabolites. A metabolite generation method was established for quantitative analysis of genistein with sulfamethoxazole as internal standard.The enzyme kinetics parameters Vmax and Km was calculated by the GraphPad Prism 5.0 software. RESULTS The metabolites in vitro incubation system was identified as genistein.The optimal time in rat liver microsomes incubation time of 40 min,the optimal protein concentration of 1 mg??mL-1,a substrate concentration of 50 ??mol??L-1.The enzyme kinetics parameters of genistein were as follows: Vmax=(0.104 2??0.003 3) ??mol??min-1??mg(pro)-1, Km=(28.96??2.80) ??mol??L-1. CONCLUSION The results indicate that genistin can be metabolited as the form of hydroxylation in rat liver microsome. Metabolite generation method is a reliable and simple method for determination of kinetic parameters of hepatic microsomal enzymes, and enzyme kinetic parameters obtained of genistin provide important parameters for further study.
  相似文献   

7.
The hypoglycemic activity of the flavonoids rich fraction of 70% alcohol extract of the Egyptian Morus alba root bark (MRBF-3) was evaluated after its oral administration to streptozotocin-induced diabetic rats. Diabetes was induced by injection of 60 mg kg−1 i.p. The administration of MRBF-3 to streptozotocin (STZ)-diabetic rats for 10 days in a dose of 200 and 400 mg kg−1 day−1 was not significant. However, administration of MRBF-3 for 10 days (600 mg kg−1 day−1) significantly reduced the amount of the glucose from control level (379 ± 9 mg/dl) to a lower level (155 ± 8 mg/dl) and significantly increased the insulin level from control (10.8 ± 0.3 μU/ml) to a high level (15.6 ± 0.3 μU/ml). The measurement of produced lipid peroxides (expressed as the amount of thiobarbituric acid (TBA) reactive substance, nmol TBARS/ml serum) indicated antiperoxidative activity of MRBF-3. The oral administration of MRBF-3 to STZ-diabetic rats significantly decreased the lipid peroxides from 6.3 ± 0.8 to 5.1 ± 0.7 nmol TBARS/ml serum. The phytochemical investigation of MRBF-3 resulted in the isolation of four hydrophobic flavonoids with one or two isoprenoid groups (log P = 5–9): morusin, cyclomorusin, neocyclomorusin, and kuwanon E, a 2-arylbenzofuran, moracin M, and two triterpenes, betulinic acid and methyl ursolate. The data obtained from this study revealed that MRBF-3 may protect pancreatic β cells from degeneration and diminish lipid peroxidation. However, this is the first biological screening of the Egyptian Morus alba root bark; further future merit studies including clinical study will be necessary in order to confirm the results obtained from this study.  相似文献   

8.
??OBJECTIVE To study the pharmacokinetics of hot-melt spray-dried andrographolide granules and compare it with andrographolide bulk drug. METHODS A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the concentration of andrographolide in plasma of rats which were respectively given micronized andrographolide and hot-melt spray-dried andrographolide granules, then the pharmacokinetic parameters were calculated. RESULTS The pharmacokinetic parameters of andrographolide after a single dose administration of micronized andrographolide and hot-melt andrographolide were as following: t1/2 were (347.33??9.32) and (390.82??8.78) min, tmax were (30.00??5.94) and (60.00??3.48) min, ??max were (1 940.14??21.21) and (1 818.22??23.64) ng??mL-1, AUC0-t were (427 515.71??37 350.03) and (426 406.31??20 577.75) ng??min??mL-1, AUC0-inf were (545 423.14??47 969.18) and (593 569.87??30 247.35) ng??min??mL-1, Vz/F were (43.48??4.75) and (44.96??3.81) kg??L-1, CL/F were (86.78??3.35) and (79.74??2.89) kg??L-1??min-1, respectively. CONCLUSION Compared with the bulk drug, the hot-melt spray-dried andrographolide granules have a longer t1/2, lower ??max and delayed tmax in rats.  相似文献   

9.
Anti-inflammatory activity of Sedum kamtschaticum   总被引:1,自引:0,他引:1  
Sedum kamtschaticum Fischer (Crassulaceae) has been used as a folk medicine in North-East Asia for treating inflammatory disorders. The present investigation was carried out to establish in vivo anti-inflammatory activity and cyclooxygenase-2 modulating activity of this plant material. The methanol extract of Sedum kamtschaticum significantly inhibited mouse croton oil-induced ear edema (24–47% inhibition at 50–400 mg/kg) and rat paw edema (24–30% inhibition at 400–800 mg/kg) by oral administration. Prednisolone (10 mg/kg) showed 54 and 36% inhibition in the same animal models, respectively. Sedum kamtschaticum also showed significant inhibitory activity against mouse ear edema induced by multiple treatment of phorbol ester for 3 days. In addition, Sedum kamtschaticum exhibited potent analgesic activity against mouse acetic acid-induced writhing (IC50=125 mg/kg), while aspirin (200 mg/kg) showed 57% inhibition. Using lipopolysaccharide-treated RAW 264.7 cells, down-regulation of cyclooxygense-2 expression was found to be one of the cellular action mechanisms of anti-inflammation by Sedum kamtschaticum.  相似文献   

10.
The butanolic and purified butanolic extracts (PBEs) of Eclipta prostrata were evaluated for their anti-venom potential. Inhibition of lethal, hemorrhagic, proteolytic, and phospholipase A2 activities of Calloselasma rhodostoma (Malayan pit viper (MPV)) venom by these extracts were determined. Demethylwedelolactone was identified as their major constituent. The butanolic extract, at 2.5 mg per mouse, was able to completely neutralize the lethal activity of 2LD50 of MPV venom, but increasing the dose diminished the effect. The PBE, at 1.5–4.5 mg per mouse, was able to neutralize the lethality of the venom at around 50–58%. Both extracts partially inhibited the hemorrhagic activity but displayed very low anti-phospholipase A2 activity and did not inhibit proteolytic activity of MPV venom.  相似文献   

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