Synthesis and anti-HBV activity evaluation of Matijin-Su derivatives with aromatic heterocycles / 中国药科大学学报

@#Hepatitis B virus(HBV)-infected hepatitis is one of the most common infectious disease worldwide. To find novel effective anti-HBV agents, a series of Matijin-Su(MTS)derivatives with aromatic heterocycles were synthesized and evaluated for their anti- HBV activities in HepG2 2. 2. 15 cells. Among them, compounds 7a(IC50=2. 94 μmol/L)and 9a(IC50=2. 21 μmol/L)exhibited more potent inhibitory activity against the replication of HBV DNA in HepG2 2. 2. 15 cells than that of lead compound MTS(IC50=11. 16 μmol/L). Notably, both 7a and 9a displayed a high selective index(SI)of 146. 39 and > 250, respectively, which were also much higher than that of MTS(SI=10. 78). Therefore, compounds 7a and 9a may be promising anti-HBV agents with safety profile for HBV infection.

Renal protective effects of superfine powder of rhodiola rosea on diabetic nephropathy in rats / 国际中医中药杂志

Objective To study the renal protective effects of superfine powder of Rhodiola rosea in diabetic nephropathy (DN)rats.Methods The DN rats model was established by one side nephrectomy and intraperitoneal injection of streptozotocin(STZ).Then rats were randomly divided into 6 groups:sham-operation group,model group,Rhodiola rosea common powder groups(3 g/kg·d-1),and superfine powder of low,medium and high dose groups (0.75、1.5、3.0 g/kg·d 1),10 rats in each group.Rats were given the relevant drugs respectively for 7 weeks.Finally the levels of fasting blood glucose (FBG),serum total cholesterol (STC),blood urea nitrogen (BUN),creatinine (Cr) and urinary protein (Upro) were detected.The kidney tissue was taken for histopathological observation.Results Compared with DN modelgroup [FBG,STC,BUN,Cr and Upro was (24.78±3.66)mmol/L,(4.07±1.32)mmol/L,(22.36±2.54)mmol/L,(86.78±7.47) μmol/L,(50.23±6.82)mg respectively],the rats in DN model group after treatment with common and superfine powder (medium and high dose groups) of Rhodiola rosea appeared different levels of improvement ofFBG [(18.67±2.74) mmol/L,(17.21 ±3.17)mmol/L,(15.48±2.46) mmol/L],STC [(3.33±0.87) mmol/L,(3.42 ± 0.74) mmol/L,(3.21 ±0.92)mmol/L],BUN [(15.43±2.04)mmol/L,(16.56±1.85)mmol/L,(12.44±1.36)mmol/L],Cr [(66.17 ± 4.43) μmol/L,(68.42 ± 5.06) μmol/L,(61.33±4.21)μmol/L] and Upro [(37.47±5.64) mg、(35.66 ± 4.72) mg,(27.37± 3.92) mg],P＜ 0.05.The pathologic changes of kidney tissue were improved,too.Conclusion Rhodiola rosea has a good renal protective effect in rats with DN.Furthermore,the superfine powder is more effective than the common powder in renal protective effects.

Pharmacokinetic Study on Hyperoside in Beagle's Dogs / 中草药·英文版

Objective To develop and validate a simple,rapid,sensitive,and reproducible HPLC method for determination of hyperoside in plasma of dogs and for the subsequent pharmacokinetic (PK) study.Methods An accurate and reproducible HPLC-UV method was developed and validated for the determination of hyperoside in plasma of dogs,using kaempferol as internal standard.The plasma samples of dogs following ig administration of hyperoside were analyzed for the detection of quercetin after enzymatic hydrolysis treatment with combined β-glucuronidase and sulphatase.The analytes were separated on a Diamonsil C18 column (250 mm × 4.6 mm,5 μm).The mobile phase consisted of methanol-buffer solution (0.1mol/L NH4Ac + 0.3 mmol/L EDTA-Na2)-acetic acid (60:40:1) and was delivered at a flow rate of 1mL/min.The UV detector was set at 370 nm and the column temperature was maintained at 35 ℃.The sample injection volume was 20 μL.Data were collected and analyzed using the ANASTAR software.PK parameters were calculated with DAS software (2.0).Results Linear relationships were validated over the range of 0.01-1μg/mL for hyperoside (r =0.9997).The intra-and inter-day precision values for all samples were within 10.0％,and the accuracies of intra-and inter-day assays were within the range of 92.4％-102.4％.The validated method was successfully used to determine the hyperoside concentration in plasma of dogs for up to 12 h,after a single ig administration (25 mg/kg).The mean PK parameters for male and female dogs were as follows:Cmax (0.18 ± 0.05) and (0.16 ± 0.05) μg/mL,AUC0-∞ (0.79 ± 0.34) and (0.86 ± 0.27) μg/(mL·h),t1/2(ka) (0.89 ± 0.41) and (0.88 ± 0.28) h,respectively.Statistical analysis on the PK of hyperoside in male and female groups showed that sex had no significant impact on the PK of hyperoside (P ＞ 0.05).Conclusion The method is able and sufficient to be used in drug PK studies of hyperoside.

Study on toxicity of hyperoside in rat embryo-fetal development / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the toxicity of hyperoside in rat embryo-fetal development, in order to provide preference for safe use of drugs during gestation period.</p><p><b>METHOD</b>Healthy pregnant rats were randomly divided into hyperosid groups (30, 175, 1000 mg x kg(-1) x d(-1)), the positive control group (cyclophosphamide, 7 mg x kg(-1) x d(-1)) and the solvent control group (1% aqueous carboxymethylcellulose). These rats were orally administered with hyperosid or vehicle during 6-15 d after gestation and subcutaneously injected with cyclophosphamide during 11-13 d. Maternal clinical sign, abortions, premature deliveries and body weight were monitored throughout gestation. At termination (gestation days 20), pregnant females were evaluated for clinical symposiums, weight change, corpora lutea count, existence and death of embryos; live fetuses were examined for gender, external, visceral and skeletal malformation and variations.</p><p><b>RESULT</b>All pregnant rats showed no significant abnormality in appearance, viscera and skeletal development. However, there was a difference between the high-dose group of hyperoside and negative control group in the fetus body weight, the length of the embryos and the length of tail (P < 0.05).</p><p><b>CONCLUSION</b>Pregnant women are suggested to cautiously use hyperoside because it shows certain impact on development of fetal rats under the experimental conditions.</p>

Protective effect of extract of Apocynum venetum on kidneys of streptozotocin-induced diabetic rats / 药学学报

The aim of this study is to investigate the effects and mechanism of extract of Apocynum venetum (AV) on kidneys of streptozotocin-induced diabetic rats. Diabetes mellitus (DM) was induced in rats by intraperitoneal injection of streptozotocin (STZ). The indexes of the blood glucose, renal function and oxidative stress were observed. The DM rats were administrated with the AV for 8 weeks, the above-mentioned indexes were detected. The blood glucose level, BUN, 24 h urine protein excretion, urine volume, renal index, renal cortex's MDA level in model groups all increased significantly. Renal cortex's SOD and GSH activities decreased significantly compared with the normal control group (P < 0.05). The above-mentioned indexes were significantly improved by the AV treatment (P < 0.05). AV have protective effects on renal function of kidneys of streptozotocin-induced diabetic rats, and maybe via inhibition of the renal oxidative stress.

Characterization and histocompatibility of acellular bone collagen matrices / 生物医学工程学杂志

A processing technique has been developed to prepare acellular bone collagen matrix (ABCM) and ABCM-PDLLA composite materials. The properties of these materials were characterized through several different methods. The histocompatibility of the materials were investigated by ELISA (enzyme linked immunosorbent assay) test and healing the defection of New Zealand white rabbit bilateral radius. The spectroscopy indicated that the major inorganic and organic components of the bone blocks were carbonated hydroxyapatite and collagen respectively,and the fatty and cellular components were. completely eliminated. The test results also revealed that the materials had good mechanical property and well-internnected pore structure, and the addition of PDLLA increased the strength of the materials. The ELISA results demonstrated that the materials had low immunogenicity in short order, and the degree of immune response caused by ABCM was greater than that by ABCM-PDLLA. All of the grafts exhibited good osteoconductive ability and a new bone form after the creeping substitution. In conclusion, two kinds of materials with good histocompatibility have been prepared, and owing to its good mechanical performance and low immunogenicity, ABCM-PDLLA is a better candidate for bone substitute and bone tissue engineering scaffold when compared with single ABCM.

Inhibition of total phenolics acid extracted from Oenanthe Javanica on HBV-DNA,cccDNA in cultured cell line 2.2.15 / 中国药理学通报

Aim To observe the anti-hepatitis B virus effect of total phenolics acid extracted from Oenanthe Javanica(OJTPA) with in vitro experiments.Methods HePG2 2.2.15 cells were treated with OJTPA,which were diluted into 500 mg?L-1,250 mg?L-1 and 125 mg?L-1 groups.The test set up positive control group(entecavir,3 mg?L-1) and normal control group.The cells of the 4 th,8 th and 4 th day ceasing treatment were collected.The content of HBV-DNA and cccDNA was determined with Quantitative Real-Time PCR method,and the inhibition rates were calculated.Results OJTPA could obviously inhibit HBV-DNA and cccDNA under the dosages used in the experiment,and showed a dose-dependent relationship.The inbhibitory rates reached the peak of 62.3% and 62.7% for HBV-DNA and cccDNA respectively,and a high inhibitory rate was retained within 3 days of OJTPA withdrawal.Conclusion OJTPA has significant inhibition on HBV-DNA and cccDNA and there is no significant rebound phenomenon.