ABSTRACT
To study the inhibitory effect of Rhaponticum uniflorum on apoptosis induced by H2O2 in HepG2 cells. Human HepG2 cells injury models were established by H2O2, then cell survival rate was assayed by MTT method; levels of LDH, ALT, and AST were detected by chemical colorimetric method;SOD activity was detected by xanthine oxidase method; GSH content was detected by dithio-bis-nitrobenzoic acid(DTNB); MDA level was detected by thiobarbituric acid (TBA) method;and the relative activities of Caspase-3, 8 and 9 were measured by Colorimetry. The expression levels of Cleaved Caspase-3(Casp-3), cytochrome(Cyto c), NF-κB, ERK, JNK, p38 MAPK, as well as the phospharylated proteins were determined with Western blotting method. The results showed that R. unifloru had no significant effect on cell viabilities of HepG2 cells at the concentrations of 25-400 mg•L⁻¹. However, H2O2decreased the cell viabilities, increased the cellular oxidative stress, and up-regulated the protein expressions of Casp-3, cytoplasmic Cyto c, p-JNK and nuclear NF-κB. As compared with the model group,R. unifloru could increase the cell viability, reduce LDH, ALT and AST leakage, reduce the MDA formation, increase the SOD and GSH levels,reduce the relative activities of Caspase-3, 8 and 9, down-regulated the protein expressions of Casp-3 and cytoplasmic Cyto c, and down-regulate the p-JNK and nuclear NF-κB levels.The results indicated that R. unifloru had the inhibitory effect on apoptosis induced by H2O2in HepG2 cells, and the mechanism maybe associated with inhibiting JNK activation and NF-κB nuclear translocation.
ABSTRACT
OBJECTIVE: To investigate the protective effect of different solvent fractions of Boschniakia rossica on acute liver injury induced by acetaminophen (APAP) in mice. METHODS: The mice were randomly assigned to the normal control, model control, bifendate (positive control), as well as groups of different solvent fractions of Boschniakia rossica. Animals were treated once daily for 7d. APAP were given intraperitoneally to the mice of groups, then the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), reactive oxygen species (ROS), lipid hydroperoxide (LPO), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), Na+-K+-ATPase, Ca2+-Mg2+-ATPase nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were detected by the colorimetric method. RESULTS: The administration with butanol soluble fraction and aqueous fraction oi Boschniakia rossica reduced the serum ALT and AST activities, increased the scrum ALB level, decreased the hepatic ROS, LPO and MDA levels, increased the CAT, GPx, SOD activities and GSH level, increased the Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of liver mitochondria, and decreased hepatic iNOS activity and NO level of liver in mice with acute liver injury. CONCLUSION: The different solvent fractions of Boschniakia rossica have protective effects on acute liver injury induced by APAP in mice, probably via anti-oxidative and anti-inflammatory activities.
ABSTRACT
This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.
ABSTRACT
This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.
Subject(s)
Animals , Humans , Male , Mice , Rats , Antineoplastic Agents , Pharmacokinetics , Pharmacology , Area Under Curve , Cell Line, Tumor , Cell Survival , Dose-Response Relationship, Drug , Guinea Pigs , Hemolysis , Mice, Nude , Micelles , Particle Size , Polyesters , Chemistry , Polyethylene Glycols , Chemistry , Prostatic Neoplasms , Drug Therapy , Pathology , Rats, Sprague-Dawley , Taxoids , Chemistry , Pharmacokinetics , Pharmacology , Treatment Outcome , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effect of soyasaponins on acute liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in mice.</p><p><b>METHOD</b>The mice were randomly divided into five groups: the normal control, the model group, the silymarin (positive control) group, and soyasaponins high and low-dose groups. They were administered with drugs once every day for 7 days. At the end of the experiment, GalN and LPS were injected intraperitoneally to all of the groups except for the normal group to establish the acute liver injury model. The pathological changes were detected with hematoxylin & eosin (HE) staining, tumor necrosis factor-alpha (TNF-alpha) was detected by ELISA method, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and the activation of Caspase-3 and Caspase-8 were detected by the colorimetric method.</p><p><b>RESULT</b>Soyasaponins could reduce the activities of serum ALT and AST, the acute hepatic injury induced by GalN/LPS, serum TNF-alpha level, hepatic NO and MDA contents, and the Caspase-3 and Caspase-8 activations of liver tissues, and increase the hepatic CAT, GPx, GST and GSH levels.</p><p><b>CONCLUSION</b>Soyasaponins shows the protective effect on acute liver injury induced by GalN and LPS in mice, which may be related to its antioxidative ability and anti-liver apoptosis.</p>
Subject(s)
Animals , Male , Mice , Alanine Transaminase , Blood , Antioxidants , Metabolism , Apoptosis , Aspartate Aminotransferases , Blood , Caspases , Metabolism , Chemical and Drug Induced Liver Injury , Metabolism , Pathology , Galactosamine , Toxicity , Lipopolysaccharides , Toxicity , Liver , Pathology , Saponins , Pharmacology , Glycine max , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To study the influence of soybean phytochemical extract containing isoflavones and soyasaponins (SPE) on blood glucose, blood lipids, plasma lipid peroxide and platelet aggregation activity in diabetic rats.</p><p><b>METHODS</b>Diabetic rats were fed with fodder containing 20 g/kg of SPE for 20 weeks. Their plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) were separated by sequential ultracentrifugation.</p><p><b>RESULTS</b>Twenty weeks after experiment, level of blood glucose, atherosclerotic index and plasma level of lipid peroxide were (11.9 +/- 0.9) mmol/L, 0.40 +/- 0.14 and (15.7 +/- 0.5) mmol/L, respectively in diabetic rats fed with SPE, significantly lower than those in control rats not fed with it, (14.2 +/- 2.0) mmol/L, 0.58 +/- 0.22 and (20.7 +/- 3.0) mmol/L, respectively. Accordingly, platelet aggregation rates induced by ADP and collagen in the two groups were (54.1 +/- 8.8)% vs (66.6 +/- 12.4)% and (58.0 +/- 7.9)% vs (69.6 +/- 9.4)%, respectively. Changes in all these indices were significantly different between the two groups.</p><p><b>CONCLUSION</b>SPE could significantly decrease blood glucose, improve atherosclerotic index, and inhibit lipid peroxidation and platelet aggregation in diabetic rats, which might be useful in prevention and control of diabetes mellitus and diabetes-associated atherosclerosis.</p>