K21. The mean t1/2(?) was (2.7?0.4) h, Vd was about 11.18 L?kg-1.The C-T profile conformed to two compartment open model. The plasma Dau concentration-time curves showed a double-peak phenomenon in all dosages of all dogswhen dauricine was given by intragastric was.The tpeak(1) was (0.8?0.6) ～(1.2?0.5) h,tpeak(2) was (5.2?3.2) ～(6.5?1.9)h,Cmax(2) 0.05) and the AUC was increased in proportion.The drug is eliminated non-linearly when the dosage is above 50 mg?kg-1, the parameters t1/2(el),CL, AUC/X0 shows great difference (P

Aim The relative bioavailability of domestic ibudilast sustained release capsules in healthy volunteers was observed.Methods A single oral dose of 20 mg of imported and domestic ibudilast sustained release capsules and 10 mg of ibudilast raw material was separately given to 12 healthy volunteers in a randomized crossover study. Ibudilast concentration in plasma was determined by HPLC method.Results The Cmax were (54.9?9.7),(60.7?9.1) and (62.2?11.5) ?g?L-1; the tmax were (3.8?0.8),(3.9?0.8) and (1.8?0.3) h;the t1/2(ke) were (1.5?1.4),(12.1?1.0) and (3.5?0.5) h,and the AUC(0～t) were (618.1?57.7),(588.1?66.6) and (233.0?46.4) ?g?h?L-1 in imported capsule group, domestic capsule group and raw material group respectively. The relative bioavailability of domestic sustained release capsules of ibudilast is (95.6?11.0)%. Conclusion The results of statistical analysis demonstrate that the imported and domestic sustained capsules have significant character of significantly sustained release and are bioequivalent.

AIMTo investigate the protective effects of sodium beta-aescin on cerebral ischemia-reperfusion injury in rats.

METHODSRats were pretreated with sodium beta-aesein for 7 d and then subjected to cerebral ischemia-reperfusion injury induced by a middle cerebral artery occlusion (MCAO). The neurological outcome was evaluated by the Longa's method; The infarct volume was assessed by hemmatoxylin-Eosin staining and the cerebral water content was measured by dry weight method. The activities of SOD, GSH-Px, CAT, Na+ -K+ -ATPase and the MDA content were measured in the cortex and hippocampus of ischemic and non-ischemic hemisphere.

RESULTSSodium beta-aescin significantly reduced the volume of cerebral infarct and water content, and ameliorated the neurological deficit (P < 0.05). In vehicle-treated rats, the activities of SOD, GSH-Px and Na+ -K+ -ATPase in the cortex and hippocampus of ischemic hemisphere were all decreased (P < 0.01) , while the CAT activity was slightly elevated and the MDA of content was significantly increased (P < 0.01) compared with the sham-operated group. After treated with sodium beta-aescin, the effects on recovery of SOD, GSH-Px, Na+ -K+ -ATPase activities were observed (P < 0.05), and the MDA content was reduced (P < 0.05).

CONCLUSIONThese results showed that pretreatment with sodium beta-aescin can attenuate brain injury and its antioxidant activity on rats which encountered cerebral ischemia-reperfusion.

Animals ; Brain ; metabolism ; Brain Ischemia ; metabolism ; pathology ; Catalase ; metabolism ; Escin ; pharmacology ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; pathology ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVETo discuss the anti-inflammatory mechanism of sinomenine on inflammatory media in joint of adjuvant arthritis rats.

METHODRats were randomly divided into the normal group and the model group, the prednisone group, the small, medium, large of sinomenine group (30, 60, 120 mg x kg(-1)). Except for the rats in the normal group, animals were modeled to adjuvant arthritiswith freund's complete adjuvant. The arthritis index (AI) and the swelling degree of paws were recorded, and the activity of IL-1, TNF and the levels of NO, PGE2 in joint fluids of secondary arthritis were determined.

RESULTCompared with the normal group, the activity of IL-1, TNF and the levels of NO, PGE2 in joint fluids of secondary arthritis were increased significantly in the model group (P < 0.05). Compared with the model group, it was shown to exert a dramatic inhibitory effect on secondary reaction of freund's adjuvant arthritis of rats, and the activity of IL-1, TNF and the levels of NO, PGE2 in joint fluids of secondary arthritis were significantly decreased in the sinomenine group (P < 0.05).

CONCLUSIONSinomenine has a remarkable treatment effect on RA. It is via NO to inhibit the activity of cytokines and decrease the level of inflammation mediators, which may be one of its curing RA mechanism.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Arthritis, Experimental ; drug therapy ; Dinoprostone ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Interleukin-1 ; metabolism ; Male ; Morphinans ; therapeutic use ; Nitric Oxide ; metabolism ; Phytotherapy ; Random Allocation ; Rats ; Rats, Wistar ; Sinomenium ; chemistry ; Synovial Fluid ; metabolism

AIMTo establish a solid phase extraction-high performance liquid chromatographic (SPE-HPLC) method for determining plasma scutellarin concentration, and study its pharmacokinetics after i.v. breviscapine in rabbits.

METHODSMethanol-water-phosphoric acid (50:50:0.5) mixture was used as mobile phase, Nucleosil C18 column (250 mm x 4.6 mm ID) was selected. The wavelength of UV detection was 335 nm. Fifteen rabbits, randomized into 3 groups, were given breviscapine i.v. at the dose of 10, 20 and 40 mg.kg-1. Scutellarin in plasma was determined by SPE-HPLC method.

RESULTSLinearity was obtained over the range of 0.02-10.0 mg.L-1 of scutellarin. The method recovery was 96.15%-99.31%; the within-day and between-day RSDs were all below 10%. After i.v. 10, 20 and 40 mg.kg-1 of breviscapine to rabbits, the concentration-time curve of scutellarin fitted to a three compartment model. The main pharmacokinetic parameters showed no significant difference between low and medium doses, but the difference was significant between high dose and other doses.

CONCLUSIONThis assay method was accurate, sensitive, simple and suitable for the measurement of plasma scutellarin concentration. The pharmacokinetic characteristics were found to fit a three-compartment model following i.v. injection of breviscapine to rabbits. The changes of drug concentration in vivo exhibited linear kinetics ove the dosage range of 10-20 mg.kg-1, but when the dosage was 40 mg.kg-1, the linear kinetic properties disappeared.

Animals ; Apigenin ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Flavonoids ; blood ; pharmacokinetics ; Male ; Rabbits

Adolescent ; Adult ; Aged ; Child ; Decision Trees ; Female ; Hepatitis B, Chronic ; diagnosis ; Humans ; Male ; Middle Aged ; Young Adult

AIMTo study the protective effect of procyanidins from the seedpod of the lotus (LSPC) on myocardial ischemia and reperfusion in rats.

METHODSMyocardial injury model was made by ligating the coronary artery for 30 min followed by reperfusion for 45 min in anesthetized rat and 30 min of ischemia followed by 30 min of reperfusion in the isolated rat heart. All animals were given the medicine or normal saline before the experiment. ET, Ang I, Ang II in the serum, the MDA content, SOD activity, NO level, the recovery rate of coronary flow (CF) and heart rate (HR) after reperfusion and CK, XO from the myocardial cells were observed.

RESULTSLSPC was shown to inhibit the release of ET, Ang II (P < 0.05) , and the increase of MDA content (P < 0.05). It was also found to increase the SOD activity (P < 0.05) and NO level (P < 0.01). LSPC was found to increase the recovery rate of the coronary flow (CF) and heart rate (HR) after reperfusion (P < 0.05 or P < 0.01), decrease the release of CK from the myocardial cells (P < 0.01), depress the XO activity of myocardial tissue (P < 0.05), as well as improve the myocyte ultrastructural pathological injury.

CONCLUSIONThe anti-ischemia effect of LSPC was related to the mechanism of scavenging the oxygen free radicals directly, cutting off the source of free radicals, reducing tissue peroxidation, stabilizing the cells membrane, depressing the production of EDCF and increasing the NO level as well.

Animals ; Biflavonoids ; isolation & purification ; pharmacology ; Cardiotonic Agents ; pharmacology ; Catechin ; isolation & purification ; pharmacology ; Coronary Circulation ; drug effects ; Loteae ; chemistry ; Male ; Myocardial Ischemia ; drug therapy ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; metabolism ; Myocardium ; enzymology ; ultrastructure ; Proanthocyanidins ; isolation & purification ; pharmacology ; Rats ; Rats, Wistar

AIMTo investigate glutamate-induced [Ca2+]i changes in cultured rat neonatal cortical astrocytes after hypoxia/reoxygenation, H2O2 or high concentration of L-glutamate injury. In the meantime, the effects of Gingko biloba extract (GbE) were examined.

METHODS[Ca2+]i changes in astrocytes were monitored by laser scanning confocal microscopy with the Ca2+ sensitive fluorescent probe fluo-3.

RESULTSAfter astrocytes were impaired by hypoxia/reoxygenation, H2O2 (50 micromol x L(-1)) or L-glutamate (0.25 mmol x L(-)), the exogenous glutamate (27 micromol x L(-1)) could not induce increase of [Ca2+]i, but decrease by (3.3 +/- 1.6)%, (81 +/- 11)% and (81 +/- 7)%, respectively. Pretreatment with GbE (10 mg x L(-1)) could not improve injured astrocytic glutamate response. But after pretreatment with GbE (100 mg x L(-1)), glutamate-induced [Ca2+]i elevation of astrocytes after hypoxia/reoxygenation, H2O2 or high concentration of L-glutamate injury were (135 +/- 98)%, (117 +/- 93)% and (89 +/- 36)%, respectively. Nimodipine (1.6 mg x L(-1)) could also reverse the abnormal response of astrocytes after different injury.

CONCLUSIONHypoxia/reoxygenation, H2O2 and high concentration of L-glutamate impaired astrocytes' response to exogenous L-glutamate, and then bidirectional communication between astrocytes and neurons could not take place. GbE could improve the abnormal responses and maintain the normal function of astroglical network. These effects support that GbE has potential beneficial actions against brain injury.

Animals ; Astrocytes ; cytology ; metabolism ; Calcium ; metabolism ; Cell Hypoxia ; Cells, Cultured ; Cerebral Cortex ; cytology ; metabolism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Ginkgo biloba ; chemistry ; Glutamic Acid ; toxicity ; Hydrogen Peroxide ; toxicity ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Reperfusion Injury

OBJECTIVETo review the effects of the active components of Chinese herbs on drug metabolizing-enzymes.

METHODRelevant research papers reported in recent years were consulted and studied.

RESULTThe drug metabolizing-enzymes cytochrome P450 and UDP-glucuronosyl transferase and glutathione S-transferase were inhibited or induced by the flavonoids, furocoumarins, and the active components extracted from salvia miltiorrhiza and hypericum perforatum, and so on, which therefore slowed or sped metabolism of other drugs in vivo and in vitro.

CONCLUSIONMuch attention should be paid to the metabolic interaction of the Chinese herbs when coadministered with other drugs.

Animals ; Cytochrome P-450 Enzyme System ; metabolism ; Flavonoids ; isolation & purification ; pharmacology ; Furocoumarins ; isolation & purification ; pharmacology ; Glucuronosyltransferase ; metabolism ; Glutathione Transferase ; metabolism ; Humans ; Plants, Medicinal ; chemistry ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo observe the effects of ginkgolides on gene expression of hepatic cytochrome P-450 in rats.

METHODSprague-Dawley rats were administered ginkgolides (100 mg x kg(-1) body weight) through oral gavage once daily for four consecutive days. The level of gene expression in liver tissues was analyzed by competitive reverse transcription-polymerase chain reaction (competitive RT-PCR).

RESULTA single and prospective band of CYP1A1, CYP1A2, CYP2B1/B2, CYP2C11, CYP2E1, CYP4A1 and cyclophilin was observed after polymerase chain reaction (PCR) when the reactive system of reverse transcription (RT) had no target RNA, which confirmed the competitor had a specific capacity to bind to the CYP or cyclophilin primer. CYP1A1 mRNA was not dectectable in the livers of untreated control rats and ginkgolides-treated rats. The levels of CYP2C11 and CYP2E1 were not changed by ginkgolides treatment. In contrast, the levels of gene expression for CYP1A2 and CYP2B1/B2 were decreased, however, the levels of gene expression for CYP3A1 and CYP4A1 in ginkgolides group were distinctly increased compared with the control.

CONCLUSIONA specific effect of ginkgolides on cytochrome P-450 gene expression was observed in this investigation. Ginkgolides had various effects on different cytochrome P-450 isoforms.

Animals ; Aryl Hydrocarbon Hydroxylases ; biosynthesis ; genetics ; Cytochrome P-450 CYP1A1 ; biosynthesis ; genetics ; Cytochrome P-450 CYP1A2 ; biosynthesis ; genetics ; Cytochrome P-450 CYP2B1 ; biosynthesis ; genetics ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System ; biosynthesis ; genetics ; Cytochrome P450 Family 4 ; Gene Expression Regulation ; Ginkgo biloba ; chemistry ; Ginkgolides ; isolation & purification ; pharmacology ; Liver ; metabolism ; Male ; Plants, Medicinal ; chemistry ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley