Aim To explore the effects of the Melittin on growth and cell cycle of SGC-7901 cells.Methods Growth inhibition effect of Melittin was evaluated using SRB in SGC-7901 cells in vitro;Melittin induced cell cycle arrest was investigated using flow cytometry assay;reverse transcription PCR(RT-PCR)was used to detect the associated protein mRNA of cell cycle.Results Proliferation activity of SGC-7901 cells was inhibited after treatment with Melittin(1,2,4,8,16,32×10~(-3) μg·L~(-1))(P<0.05 or P<0.01)for 24 h;Flowcytometry analysis revealed that SGC-7901 cells accumulated in the G_2/M phase after treatment with Melittin(4,8×10~(-3) μg·L~(-1))for 24 h;the expression of CylinB1,CDK1 and Cdc25c mRNA were decreased.Conclutions Proliferation activity of SGC-7901 cells was inhibited by Melittin,which may be related to the inhibitory effect of Melittin on associated protein transcription in the G_2/M stage of SGC-7901 cells.

Aim To observe the protection effect of Tribulus terrestris saponin monomer B (TTSMB) on cadiocytes impaired by hypoxia-reoxygenation (H/R).Methods Cadiocytes of neonate rat were cultivated for 72 hours and divided into normal control group, H/R group,GSTT 100 mg·L~(-1) group and TTSMB 10,1,0.1 nmol·L~(-1) group.Morphocytology change of cadiocytes was observed after the treatment.Cadiocyte survival rate was detected with MTT colorimetric method.Levels of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), malondialdehyde (MDA), and activity of superoxide dismutase (SOD) were determined. Apoptosis rate was detected with flow cytometry.Expression of caspase-3 was examined with western blot.Results Compared with the control group, the survival cell number in H/R group decreased obviously, content of CK,LDH, AST, MAD increased, and activity of SOD decreased (P<0.01).Compared with the model group, the survival cell population increased in TTSMB 10,1,0.1 nmol·L~(-1) group (P<0.05 and P<0.01).Contents of CK, LDH, AST, MAD decreased, whereas the activity of SOD increased (P<0.05 and P<0.01).Apoptosis rate and expression of caspase-3 also reduced in TTSMB 10,1,0.1 nmol·L~(-1) group.Conclusion TTSMB has significant cadiocytes protective effect against H/R and inhibits cadiocyte apoptosis,and the mechanism depends on the effect against oxygen free radical.

Aim To investigate the apoptotic mechanism and polyamine transporter recognition of 3-nitro-naphthalimide norspermine conjugate (NNINspm),a novel naphthalimide-polyamine conjugate, in HepG2 cells.Methods The cytotoxicity of NNINspm was assessed by MTT assay.Cell cycle distribution and apoptosis were measured by flow cytometry.The protein expression of cytochrome C,14-3-3,Bad,Bcl-xL,mTOR,p70S6K,Cdk4,p27~(kip1),Akt,Caspase-3,Caspase-9 was evaluated by Western blot.The translocation of Akt was detected by high content screening (HCS) analysis.Results NNINspm induced HepG2 cells apoptosis via Akt dephosphorylation and then triggered a series of signal events, such as Bad dephosphorylation, dissociation of 14-3-3 and Bad, and then binding to Bcl-xL,which finally resulted in mitochondrial disruption,cytochrome c release and caspase cascade activation.Furthermore,the NNINspm-mediated cell cycle arrest was due to mTOR and p70S6K dephosphorylation,Cdk4 down-regulation and p27~(kip1) up-regulation.Conclusion NNINspm induces HepG2 cell apoptosis via PI_3K/Akt signal pathway.

Vascular endothelial cells and smooth muscle cells,structurally and functionally closely related,are two main cells of vascular wall.While the interaction between cycling factors and vascular wall cells can lead to the occurrence of atherosclerosis.The injury of endothelial cells results in secretory dysfunction and abnormal proliferation of smooth muscle cells which narrows the cavity of blood vessel and cause spasm.This is the common pathological basis of the occurrence and development of atherosclerosis and other vascular diseases.In the pathological state of atherosclerosis,the proliferation of smooth muscle cell will be affected by what the vascular endothelial cells secrete,like growth factors,cytokines,and vasoactive substances.This paper gives a comprehensive overview of the latest research advances in this field.

Ginko biloba extract is an active compound with broad biological function.This review summarizes the immuomodulatory effect of Ginko biloba extract on immune organ development, monocyte macrophage, natural killer cell, humoral immunity, cellular immunity, cytokines, red cell immunity and mucosal immunity.

Aim To establish two new rat models of visceral hypersensitivity in IBS by two chemical irritants.Methods Acetic acid or mustard was infused for six days in intestines of adult rats.After modeling,the rectal distention was performed and the thresholds of abdominal withdrawal reflex were measured.The frequency,peak value,peak-nadir value and area of the gastric and enteric electrical activity were recorded.And the contents of 5-HT in the blood serum were detected.Results Compared with the control group,the colon and rectum's sensitivity(P<0.05)and the frequency(P<0.01) of the acetic acid model were heightened.Meanwhile,the colon and rectum's sensitivity(P<0.01),the frequency(P<0.01),peak value(P<0.05),peak-nadir value(P<0.01)and area(P<0.01),and the contents of 5-HT(P<0.05)in serum of the mustard model were all changed,which indicated the increasing of sensitivity of the model.The colon and rectum's sensitivity,the gastric and enteric electrical activity and the contents of 5-HT in serum of the proving group were recovered to some extent.Conclusion The new rat model of visceral hypersensitivity in IBS is successfully set up by stimulating the intestines of adult rats with chemical substances.

Aim To assay the mutagenicity of Enphorbia lunulata(EL) decoction and to modify the Ames test for evaluation the mutagenicity of herbal medicine samples.Method The mutagenicity of EL decoction was assayed by standard Ames test; the teratogenicity was done by mammalian bone marrow chromosomal aberration test. In modified Ames test system,the influence of histidine EL decoction was excluded by additional negative control, in which the test media was supplied with histidine (histidine amount equaled to the histidine in different concentration of EL decoction).Result The mutagenicity of EL decoction was positive in the standard Ames test. The teratogenicity of EL decoction was negative in mammalian bone marrow chromosomal aberration test. By the modified Ames tests,the mutagenicity of EL decoction was negative.Conclusion The standard Ames test is not suitable for evaluating the mutagenicity of EL decoction, but the modified Ames test is. The mutagenicity in vitro and the teratogenicity in vivo of EL decoction are all negative.

Aim To investigate the effects of CYP2C19 polymorphism on the pharmacokinetics and comparative bioavailability of omeprazole in Chinese population.Methods Eighteen healthy male volunteers were selected,of whom 6 were CYP2C19 wild type(w/w),6 were CYP2C19 heterozygous variant(w/m) and the rest were CYP2C19 homozygous variant(m/m).A randomized two-period crossover study was performed.Subjects were assigned to receive test or reference omeprazole as a single oral dose of 40 mg randomly.After a washout period of one week,subjects received the alternative omeprazole formulation.Multiple blood samples of 3 ml were obtained over 12 h after dosing and plasma concentrations of omeprazole were measured by LC/MS method.The modeling of individual pharmacokinetics and the pharmacokinetic parameters of omeprazole were estimated by 3P97.Results The AUC and Cmax of reference omeprazole formulation in w/w,w/m,m/m groups were 1178.44±340.24,2328.10±1011.83,5062.02±1097.29 μg·h·L~(-1) and 602.87±118.25,926.43±134.48,1406.29±233.58 μg·L~(-1),respectively,with significant differences among the three groups(P<0.05).Significant differences were also observed in other pharmacokinetic parameters such as k_e、CL/F、t_(1/2) and Vd/F among the three groups(P<0.05).With regard to test omeprazole formulation,the AUC and C_(max) in w/w,w/m,m/m groups were 1224.82±531.67,2723.34±519.29,5692.49±1575.35 μg·h·L~(-1) and 618.74±231.43,910.67±125.99,1303.31±152.01 μg·L~(-1),respectively,which,as well as k_e,CL/F,t_(1/2) and Vd/F were significant different among the three groups(P<0.05).No significant differences were observed in comparative bioavailability among groups with the values of 94.29%±14.06%,93.08%±11.22%,91.84%±13.03% in w/w,w/m,m/m groups respectively(P>0.05).Conclusions Different CYP2C19 genotypes,leading to functional heterogeneity of CYP2C19,may affect pharmacokinetic profile of omeprazole.Therefore,genotyping CYP2C19 gene before omeprazole therapy will be of great benefit for optimizing individual therapy regimen.There is no significant difference of omeprazole comparative bioavailability with regard to CYP2C19 genetic polymorphism.

Aim To investigate the protective effect of catechin on cerebral ischemia-reperfusion injury in rats and its mechanism.Methods 40 rats were randomly divided into 5 groups:sham operation group,model group and 50,100 and 200 mg·kg~(-1) catechin groups,with 8 rats in each group.The model of focal cerebral ischemia-reperfusion in rats was established with modified sutured-occluded method.The rats in catechin groups were injected with catechin at the matched concentration.The rats in sham operation group and model group were injected with saline.And all rats were given more time in 2 hours after ischemia.Rats were sacrificed for histologic examination after the behavioral test,and their brains were taken to assay the activities of MPO and NOS.Results Catechin at different dosages(50,100 and 200 mg·kg~(-1))could obviously decrease neurological deficit score,repair histological injury,and reduce the activities of MPO and NOS in rats of focal cerebral ischemia-reperfusion injury.Conclusions Catechin can relieve the cerebral ischemia reperfusion injury,and its mechanism may be partly related to the effects of its antiinflammation and antioxidation.

Aim To investigate the protective effect and the underline mechanisms of total flavonoids from Sorbus Tianschanica L leaf (TFST) against myocardial ischemia/reperfusion (I/R) injury.Methods The I/R injury model of rat isolated heart was prepared by improved Langendorff retrograde perfusion method.Following the treatment,the coronary blood flow levels (CF),left ventricular developed pressure (LVDP) and maximal rise/fall rate of left ventricular pressure (±dp/dt_(max)) were monitored as the myocardial function.The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardial tissue were measured by the commercial kits. The in vitro anti-oxidative capacity of TFST was detected by the DPPH and lipid peroxidation reaction system.Results Compared with I/R injury group, pre-incubation with TFST (6.0 mg·L~(-1)) significantly improved the LVDP,±dp/dt_(max) and CF during reperfusion. TFST (6.0 mg·L~(-1)) treatment significantly increased the SOD activities and reduced the MDA levels in myocardium tissue.Moreover,TFST (from 6.25 to 100.0 mg·L~(-1)) scavenged the DPPH, hydroxyl radical and superoxide anion free radicals, and inhibited the lipid peroxidation reaction in a concentration-dependent way.Conclusions All the results demonstrate that TFST possesses the cardioprotective effect on ischemia/reperfusion injury.This efficacy may be due to its antioxidative activity.