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??OBJECTIVE To assess the impact of chrysin and naringenin on the pharmacokinetics (PK) of saquinavir (SQV), a substrate of P-glycoprotein (P-gp), in rats. METHODS Fifteen rats were randomized into 3 groups of equal size, and administered orally 30 mg??kg^-1 SQV with or without 40 mg??kg^-1 chrysin or naringenin. The PK of SQV was assessed using non-compartmental analysis and the plasma concentrations of three groups were determined by LC-MS/MS. RESULTS The PK parameters values of SQV, SQV+ naringenin, SQV+ chrysin are as follows:AUC_0-t,882.91,861.32,934.84 ng??h??mL^-1; AUC_0-??,903.97,865.90,947.92 ng??h??mL^-1; ??_max,177.72,89.8,130.72 ng??mL^-1; t_max,1,2,0.5 h;t_1/2,11.73,12.61,13.33 h; MRT_0-??,27.09,31.63,26.60 h; CL/F,21.65,21.45,20.62 mL??kg^-1??h^-1. CONCLUSION Double peak phenomenon is observed in the plasma SQV profiles. Our study demonstrates that chrysin and naringenin can not significantly affect the SQV oral bioavailability and SQV PK profiles in rats.     

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??OBJECTIVE To explore the effects of Dracocephalum total flavonoids(TFDM) on myocardial ischemia/reperfusion injury(MIRI)induced autophagy in rat. METHODS In vivo MIRI model was established with ischemia 30 min and reperfusion 120 min, by ligation of left anterior descending coronary artery. TFDM(30 mg??kg^-1??d^-1) and autophagy activator(1 mg??kg^-1??d^-1) or inhibitor(25 mg??kg^-1??d^-1) pretreatment was given before making the model. The MIRI-induced infarct size, the activities of lactate dehydrogenase(LDH), creatine kinase isoenzyme(CK-MB) in plasma and apoptosis protein caspase-3 in tissue and the expression level of autophagy-related proteins LC3, Beclin-1 were observed. RESULTS Compared with model group, the experiment revealed that autophagy inhibitor alleviated MIRI-induced myocardial damage by decreasing the infarct size, myocardial enzyme LDH and CK-MB leak; and reducing apoptosis protein caspase-3 activity level. In addition, TFDM pretreatment significantly inhibited the expression of autophagy-related proteins LC3 and Beclin-1. CONCLUSION TFDM shows inhibitory effects on MIRI-induced autophagy,which may play an important role in the protection against MIRI.     

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??OBJECTIVE To develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties of araloside A. METHODS Araloside A was administered in a dose of 50 mg??kg^-1 via gastric in fusion and 5 mg??kg^-1 by intravenous injection in rats.Araloside A was analyzed by a validated LC-MS/MS method in plasma after intravenous and intragastric administration. The pharmacokinetic parameters were evaluated by software DAS 3.0. RESULTS The RESULTS of pharmacokinetic study showed that the linear range of araloside A was good in 1.0-10 000.0 ??g??L^-1(r>0.994 8). The specificity, precision and accuracy, matrix effect and extraction recovery rate and stability all meet the requirements. The main pharmacokinetic parameters for intragastric administration with araloside A 50 mg??kg^-1 and intravenous injection of araloside A 5 mg??kg^-1 were as follows:t_1/2 was(8.65??3.22) and(2.00??0.21)h, AUC_0-t was(277.14??101.00) and (21 194.59??4 385.13)ng??h??L^-1, MRT_0-t was (7.88??0.64) and (1.21??0.11)h, Vd/F was (2 229.99??1 013.97) and (0.71??0.20)L??kg^-1, CL/F was(149.11??62.28) and (0.24??0.05) L??h^-1??kg^-1, respectively; ??_max was (32.68??10.74) ??g??L^-1 for intragastric administration and t_max reached(1.21??0.70) h, oral bioavailability of araloside A was about 0.14%. CONCLUSION The LC-MS/MS method established is specific and sensitive, and can be successfully applied in basic pharmacokinetic study of araloside A in rat plasma.     

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??OBJECTIVE To investigate the antitumor effect and molecular mechanism of ginsenoside Rg1 pyrolysis products (HPPRg1) on H₂₂ tumor bearing mice. METHODS To establish tumor model of transplanting H₂₂ tumor-bearing mice and observe the anti-tumor effects of HPPRg1, H₂₂ tumor-bearing mice were randomly divided into groups of control, model, cyclophosphamide (CTX, 30 mg??kg^-1), low dosage of HPPRg1 (HPPRg1-L, 10 mg??kg^-1), middle dosage of HPPRg1 (HPPRg1-H, 20 mg??kg^-1) and high dosage of HPPRg1 (HPPRg1-H, 40 mg??kg^-1) groups, respectively. Through evaluating inhibition rates of tumors, organ indices, and levels of TNF-??, IFN-?? and IL-2 to observe the anti-tumor effect of HPPRg1. In addition, H&E and Hoechst 33258 straining were used to observe the apoptosis of H₂₂ tumor cell. RESULTS Compared with the model group, the three dose groups of HPPRg1 can inhibit tumor proliferation. Mainly through the inhibition of tumor cell proliferation and pro-apoptosis to exert anti-tumor effect. CONCLUSION HPPRg1 has a significantly inhibitory effect on H₂₂ tumor-bearing mice, the mechanism may related to promote apoptosis of tumor cells and improve immunity.     

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??OBJECTIVE To establish an HPLC-UV method for the simultaneous determination of valsartan and nifedipine in rats plasma, so as to study the pharmacokinetic interaction between valsartan and nifedipine and to provide useful information for clinical practice. METHODS Eighteen male Wistar rats were divided into three groups: valsartan group(16 mg??kg^-1), nifedipine group (4.2 mg??kg^-1) and combined group (containing valsartan 16 mg??kg^-1, nifedipine 4.2 mg??kg^-1). Plasma samples were collected at 0, 0.08, 0.16, 0.25, 0.5, 0.75, 1, 2, 4, 8, 10, 24 h after the drug administration. An HPLC with UV detection method was developed to determine the concentration of valsartan and nifedipine in rat plasma, and the pharmacokinetic parameters were calculated using non-compartment model. RESULTS Compared with single valsartan group, the pharmacokinetic parameters ??_max and AUC_0-t of the combined group had a significant increase(P<0.05), while Tmax and CLz/F had a significant decrease(P<0.05). Compared with single nifedipine group, the pharmacokinetic parameters t_1/2z/h had a significant decrease(P<0.05), while other pharmacokinetic parameters had no significant differences. CONCLUSION Combination of valsartan and nifedipine could significantly improve the valsartan in rats plasma concentration and bioavailability, increase absorption and decrease excretion , while nifedipine shows no pharmacokinetic change in rats except shortened half-life.     

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??OBJECTIVE To investigate the influence of tripterygium glucoside tablet on the pharmacokinetics of atorvastatin in rats. METHODS Twelve rats were equally randomized to two groups (six rats in each group), including the atorvastatin-only group (A) and the tripterygium glucoside tablet and atorvastatin group (B). Animals in group A were administered according the oral dose of 2 mg??kg^-1; and animals in group B were administered at an oral dose of atorvastatin (2 mg??kg^-1)and tripterygium glucoside tablet (2 mg??kg^-1). Blood samples were collected into a heparinized tube via the oculi chorioideae vein at different time points after drug administration, and the plasma concentration of atorvastatin were determined using HPLC-UV. Finally, the pharmacokinetic profiles of atorvastatin were calculated and compared. RESULTS Compared with the atorvastatin-only group(A), the pharmacokinetic parameters of the tripterygium glucoside tablet and atorvastatin group(B) have changed greatly. ??_max of atorvastatin increased from (4.77??0.64) to (7.79??0.61) mg??L^-1, and AUC_0-t increased from (12.82?? 3.50) to (27.39??5.76) mg??h??L^-1, at the same time, t_max was extended from (0.25??0.03) to (0.52??0.07) h, t_1/2 was prolonged from (2.39??0.19) to (5.09??1.35) h, MRT was extended from (2.93??0.23) to (4.36??0.44)h. It indicates that the metabolism of atorvastatin may be suppressed. CONCLUSION The RESULTS indicate that tripterygium glucoside tablet could influence the pharmacokinetics of atorvastatin when atorvastatin and tripterygium glucoside tablet are used concomitantly. This study could be used for clinical medication guidance of tripterygium glucoside tablet and atorvastatin to avoid the occurrence of adverse reactions.     

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??OBJECTIVE To investigate the effects of microwave radiation on learning and memory abilities in mice,and to study pilose antler peptide??s intervention. METHODS Fifty mice were divided into five groups randomly, designated as control group, radiation group, pilose antler peptide (25, 50, and 100 mg??kg^-1) groups. Learning and memory impairment model in mice was established by microwave radiation of 2 450 MHz average surface power, 10.0 mW??cm^-2 for 90 min every day for 28 d .The radiation rats were treated with low-, mid-, and high-dose (25, 50, and 100 mg??kg^-1) pilose antler peptide by sc injection for 28 d. The learning and memory ability of mice was determined by avoiding darkness experiment and Y maze experiment.The contents of S100B, tumor necrosis factor-??(TNF-??), interleukin-10(IL-10), malondialdehyde (MDA), and nitric oxide(NO) in the brain of mice were determined respectively after the behavioral experiments. RESULTS Compared with control group, radiation group could shorten the latency of avoiding darkness experiments, increase the numbers of errors both in avoiding darkness experiment and in Y maze experiment. Radiation group could rise the contents of S100B ,TNF-??, IL-10, MDA and NO in the brain of mice (P<0.05 or P<0.01). Compared with radiation group, pilose antler peptide (50, 100 mg??kg^-1) groups could lengthen the latency of avoiding darkness experiments, significantly shorten the numbers of errors both in avoiding darkness experiment and in Y maze experiment, and reduce the contents of S100B ,TNF-??, MDA and NO, increase the content of IL-10 in the brain of mice (P<0.05 or P<0.01). CONCLUSION Pilose antler peptide could significantly perfect the learning and memory ability of mice exposed to microwave radiation. The mechanism may be related to its anti-oxidative actions by anti-inflammatory action , further lowering neurotoxic effects of NO.     

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??OBJECTIVE To investigate the anti-depressant effect of schisandrin A in rats with depression caused by chronic unpredictable mild stress(CUMS)as well as the relevant mechanism. METHODS The depression-like rat model using CUMS was established. Rats were randomly divided into control, CUMS model, CUMS+fluoxetine (10 mg??kg^-1)and CUMS + schisandrin A (25, 50, 100 mg??kg^-1)groups. Drugs or vehicle were administrated after stress procedures for 21 d. Open-field test (OFT), sucrose preference tests (SPT)and forced swim test (FST)were used to evaluate the anti-depressant effects of schisandrin A. The reactive oxygen species (ROS)and prostaglandin E₂ (PGE₂) level as well as superoxide dismutase (SOD) and catalase (CAT)activities in hippocampus were determined by ELISA methods. IL-1??, TNF-??, and IL-10 expression were measured by real time qPCR and Western blot analysis. RESULTS Behavioral test indicated that crossing score and rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than control group (P<0.01), while immobility time in FST was significantly increased (P<0.01). Compared with those in control group, the ROS and PGE₂ level increased significantly (P<0.01), SOD and CAT activities decreased significantly (P< 0.01),the mRNA and protein level of IL-1??, TNF-??, and IL-10 were increased significantly (P<0.05 or P<0.01)in rats of CUMS. CONCLUSION Schisandrin A and fluoxetine could ameliorate those changes induced by CUMS. Schisandrin A could improve the depression-like behaviors of rats induced by CUMS, of which the mechanism might involve the antioxidant and anti-inflammatory effects.     

金黄霉素A对脂多糖诱导小鼠急性肾脏炎症的作用及其可能机制

目的 研究金黄霉素A(chrysomycin A,Chr-A)对脂多糖(lipopolysaccharides,LPS)诱导小鼠急性肾脏炎症反应的作用及机制。方法 BALB/c小鼠随机分为正常对照组、LPS模型组、Chr-A 3 mg·kg^-1和10 mg·kg^-1给药组。Chr-A连续给药7 d后,LPS模型组和各Chr-A给药组腹腔注射5 mg·kg^-1的LPS,6 h后取血清和肾脏组织进行检测。检测血清尿素氮(BUN)评价肾功能;ELISA法检测肾组织中白细胞介素1β(Interleukin-1β,IL-1β)、白细胞介素6(Interleukin-6,IL-6)、单核细胞趋化蛋白1(monocyte chemoattractant protein,MCP-1)以及肿瘤坏死因子α(tumor necrosis factorα,TNF-α)水平;Western blot检测炎症相关蛋白环氧合酶2(cyclooxygenase 2,COX2)、NLRP3炎性小体及嘌呤能离子通道型受体7(P2X7)的表达。结果 Chr-A剂量依赖性降低LPS刺激引起的血清BUN水平升高;此外,Chr-A剂量依赖性降低LPS刺激引起的肾脏组织中IL-β,IL-6,TNF-α,MCP-1及COX2炎症因子的升高;进一步研究发现,Chr-A显著下调炎症通路相关蛋白P2X7和NLRP3的表达。结论 Chr-A具有抗LPS诱导的小鼠急性肾脏炎症反应作用,机制可能与下调炎症蛋白P2X7和NLRP3相关。