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Aim To study the hypoglycemic effect and the mechanism of novel sulfonyluric compound G-003. Methods ① After compound G-003 was givenig for 7 days, the levels of fasting plasma glucose of normal mouse was assayed with glucose oxidase kit. ② Rat pancreatic islets, adipocytes and mouse heaptocytes were isolated and cultured. Effects of compound G-003 on insulin release, glucose transport and utilization and glycogen synthesis were studied. Results Compound G-003 markedly decreased the levels of fasting plasma glucose of normal mouse, stimulated isolated pancreatic rat islets to release insulin and increased glucose transport and utilization in isolated rat adipocytes. Compound G-003 has no effect on glycogen synthesis in isolated mouse hepatocytes. Conclusion Compound G-003 has a significantly hypoglycemic effect. The hypoglycemic mechanism of novel compound G-003 may be attributed to stimulate secretion of insulin and increase glucose transport and utilization.
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AIM: To approach the antiobesity action and mechanisms of the daidzein derivative: LRXH609(LRX).METHODS: The body weight,Lee′s index,total weight of celiac fat tissue,food intake,serum glucose and lipids in obese rats induced by a high-fat diet were measured and the antiobesity action was tested after LRX was administered for 30 days.3T3-L1 pre-adipocytes were induced by in vitro culture,the effects of LRX on cell proliferation,lipogenesis,lipolysis were observed.RESULTS: The body weight,Lee′s index,fat tissue weight in obese rats were significantly decreased by LRX,and the concentrations of TC,FFA in serum were decreased,the proliferation of 3T3-L1 pre-adipocytes was inhibited,the activities of hormone sensitive lipase in 3T3-L1 pre-adipocytes were significantly elevated,the glycerine release from adipocytes was promoted and the concentrations of TG in adipocytes were decreased.CONCLUSION: LRX plays a role in antiobesity action and regulating blood lipid and the mechanism might be related to inhibiting proliferation and differentiation of pre-adipocytes,stimulating TG decomposition by activating hormone-sensitive lipase and decreasing the TG storage in adipocyte.
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AIM: To study the protective effect of medicinal serum of Jiangtang compound recipe on endothelial cells which were damaged by H2O2. METHODS: The effects of medicinal serum of Jiangtang compound recipe on cell viability, concentration of malondialdehyde (MDA), NO, endothelin-1 (ET-1) and activity of superoxide dismutase (SOD) were determined for human umbilical vein endothelial cells (ECV304) damaged by H2O2. RESULTS: The medicinal serum of Jiangtang compound recipe significantly improved the structural change of ECV304 cells damaged by H2O2, suppressed the production of MDA and the content of ET-1, increased activity of SOD and the rate of animate cells, and promoted secretion of NO. CONCLUSION: The medicinal serum of Jiangtang compound recipe can resist the injury of ECV304 caused by H2O2, playing a role in the protective effect.
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AIM:To study the effect of antioxidation in subacute aging model mice with Jiangtang compound recipe which composed of kudzuvine root, heartleaf houttuynia herb and Evonymus alatas. METHODS: By using the D-galactose-induced aging mice, the body weight,the content of malondialdehyde (MDA),the activities of superoxide dismutarse(SOD) and glutothine peroxidase(GSH-Px) in serum and tissues were determined. RESULTS:To the model mice, Jiangtang compound recipe (14, 7 g/kg, i.g.) reduced the content of MDA, enhanced the activities of SOD and GSH-Px in serum and tissuses, inhibited the decrease of body weight. CONCLUSION: Jiangtang compound recipe shows a remarkable anti-oxidative effect on the D-galactose-induced aging mice.
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AIM:To study the effects and mechanisms of a novel sulfonylureous compound 1 ｛4 [2 (4 bromobenzenesulfonaminoethyl)phenylsufonyl｝ 3 (trans 4 methylcyclohexyl) urea, G004, on antithrombosis. METHODS: The influence of compound G004 on the vasoconstrictor action, platelet aggregation and thrombosis formation was studied. The effects of compound G004 on the tail vein bleeding time in mice was examined. The influence of compound G004 on the release of prostanglandin I 2 and thromboxan A 2 from ECV304 cells was investigated. The measurement of cytosolic free Ca 2+ in attached ECV304 cells loaded with Fluo3/AM was carried out. RESULTS: Compound G004 did not inhibit the contraction of rat aorta rings induced by norepinephrine or potassium chloride, but potently inhibit human platelet aggregation challenged by arachidonic acid and adenosine diphosphate. Compound G004 significantly prolonged the tail vein bleeding time in mice and occlusion time of carotid artery in experimentally thrombotic rats. Compound G004 reduced mice mortality induced by the collagen plus epinephrine in a dose dependent manner. Compound G004 enhanced PGI 2 release and reduced TXA 2 secretion from ECV304 cells. G004 had no effect on the increase of cytosolic free Ca 2+ induced by patassium chloride. CONCLUSION: The compound G004 has a remarkable antithrombotic effect in vivo. Its active mechanism may be attributed to inhibition of platelet aggregation, enhancing PGI 2 generation and decreasing TXA 2 secretion from human umbilical vein endothelium.
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AIM:To investigate the effects of a novel thiazolidinedione ANY2 on glycometabolism in HepG2 cells.METHODS:HepG2 cells are exposed to high concentrations of insulin for 24 h to build the model of insulin-resistance(IR-HepG2).The effects of ANY2,including glucose consumption(GC),gluconeogenesis and glucolysis were tested in this model.RESULTS:ANY2 could dose-dependently enhance GC in IR-HepG2 cells at high,medium and low levels of glucose.Compared with Modle Group,ANY2 increased IR-HepG2 cells glycogen synthesis significantly only in high dose group.It inhibited gluconeogenesis from lactic acid,but increased the production of lactic acid and the activity of pyruvate kinase(PK)in glucolysis.CONCLUSION:Compound ANY2 has remarkable effects on improving glycometabolism in IR-HepG2 cells.
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Objective To observe the effects of cistanchis glycosides on scopolamine -induced impariment of learning and memory and on sodium nitrite -induced impariment of learning and memo ry consolidation in mice.Methods Step down test was performed to reflect th e learning and memory of mice.Cistan chis glycosides were administered c onsecutive-ly for 30days.The mice were trained o n the 29th day and measurements were c arried out on the 30th day .Latent period and number of errors within 5min were noted.Scopolamine was given by intr aperitoneal injection 15min before train-ing,and sodium nitrite was administered subcutaneously right after trainin g.Results(1)Compared with model mice in-duced by scopolamine,cistanchis glycosides 200and 400mg /kg together with piracetam 600mg /k g considerably in-creased latent period and decreased error times.Cistanchis glycosides100mg /kg also increased latent time but decreased error times to some extent.(2)Compared with model mice induced by s odium nitrite,cistanchis glycosides 200and 400mg /kg increased latent time significantly but had no significant effect on the error times.Cistanchis glycosides 100mg /kg decreased latent time and error time s to some extent.Conclusion Cistanchis glycosides could obviou sly improve scopo-lamine -induced impariment of learn ing and memory and on sodium nitrite -induced impariment of learning and memory in mice.
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AIM To study the pharmacokinetic characters following oral administration of colon specific tinidazole tablets in healthy dogs METHOD The plasma and intestine content concentration of tinidazole was determined by RP HPLC method following a single oral dose of 500 mg of two formulations given to each dogs in an open randomized two way crossover design RESULT The main pharmacokinetic parameters of test and reference tablets were as follow: T max : (6 3?1 2) h and (2 4?1 1) h; C max : (46 23?8 93) mg?L -1 and (58 08?14 65) mg?L -1 ; AUC 0-t : (423 21?93 08) mg?h?L -1 and (458 22?112 07) mg?h?L -1 The relative bioavailability of tinidazole colon specific enteric tablets was 92 9%?6 6%. 6 5 h after intake of colon specific tablets, there were a great deal of tinidazole in dogs colon but almost no tinidazole in small intestine CONCLUSION The result demonstrated that the colon tropic effect of the tablets is significant in dogs
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Aim To establish an analytical method for determination of compound G004 concentration in plasma and investigate its application to pharmacokinetics and absolute bioavailability in rats.Methods 5.0 and 2.5 mg?kg~(-1) compound G004 were given via ig and iv respectively to SD rats.Blood samples were collected at various time points after administration.Plasma concentration of compound G004 in rats was determined by LC-ESI-MS.Pharmacokinetic parameters were calculated by DAS program and absolute bioavailability was also calculated.Results The method was linear over the range of 0.02～5 mg?L~(-1)(r~2=0.9995).The recovery of compound G004 in rat plasma was more then 87%.Intra-and inter-day precision,expressed as the relative standard deviation(RSD) was less than 15%.After iv compound G004,the main pharmacokinetic parameters T_(2),CLs,V_d,AUC_((0-∞)) were(1.91?0.65) h,(0.36?0.22) L?h~(-1),(0.78?0.36) L ?kg~(-1),(9.52?3.53) mg?L~(-1)?h~(-1) respectively.The major pharmacokinetic parameters T_(max),C_(max),T_(2),AUC_((0-∞)),MRT_((0-12h)) were 0.83 h,(3.33?0.80) mg?L~(-1),(1.77?0.21) h,(10.04?2.43) mg?L~(-1)?h~(-1) and(2.75?0.31)h after ig compound G004.The absolute bioavailability was 52.69% after correction of dosage.Conclusion The method is sensitive and specific which is applicable to pharmacokinetic analysis of compound G004 in rats.