Anti-fatigue Effect of Water Extract from Centella asiatica(L.)Urban on Mice

[Objectives]To study the anti-fatigue effect of water extract from Centella asiatica(L.)Urban on mice.[Methods]After intragastric administration of low,medium and high concentration of water extract from Centella asiatica(L.)Urban for 14 d,the rotarod time and the content of serum lactic acid in mice were determined,respectively.[Results]Compared with the control group,the rotarod time of mice in the low and medium concentration groups was significantly prolonged(P<0.05),but there was no significant difference between the control group and the high concentration group;the content of serum lactic acid in the medium concentration group was significantly lower than that in the control group(P<0.01),but there was no significant difference between low concentration group and high concentration group and the control group.[Conclusions]A certain concentration of water extract from Centella asiatica(L.)Urban had a good anti-fatigue effect.

Antitumor effects of artesunate on human breast carcinoma MCF-7 cells and IGF-IR expression in nude mice xenografts

Purpose： The objective of this study was to investigate the anti-tumor effects and analyze the mechanism of artesunate （ART） action on breast cancer in vivo using tumor transplanted nude mice. Methods： The human breast tumor cell line MCF-7 was transplanted into nude mice, and the animals were treated with various doses of ART alone or in combination with cyclophosphamide （CTX） or normal saline （NS）. The tumor inhibitory effects were observed and compared, and the ultrastructural morphology of the transplanted tumor cells was observed by electron microscopy. The apoptosis rates and cell cycle status were detected by flow cytometry （FCM）. The expression of apoptosis-related proteins p53, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry and IGF-IR was detected by western blot. The expression correlation for these proteins was also analyzed. Results： The tumor inhibition rates in the low dose ART group, high dose ART group, CTX group and combined drug therapy group were （24.39±10.20）%, （40.24±7.02）%, （57.01±5.84）% and （68.29±5.1）%, respectively. The cell cycle was arrested in phase G0/Gt after treatment with ART. The expression of Bcl-2 was significantly reduced, and the expression levels of Bax and Caspase-3 were significantly increased in the ART group compared to the negative control saline group. There was no significant difference detected in p53 expression. The Bcl-2 level was negatively related to Bax and Caspase-3. The western blotting results showed IGF-IR downregulation. Conclusions： ART inhibits the growth of MCF-7 breast tumor cell xenografts in nude mice. The anti-tumor mechanism of ART for human breast carcinoma in nude mice might be correlated with the alteration of apoptosis related protein expression, which may further induce apoptosis and inhibit cell proliferation.

Protective Effects of Shikonin on Brain Injury Induced by Carbon Ion Beam Irradiation in Mice

Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group （P〈0.01）, while obviously reduced the MDA and PCO contents and the RO$ levels derived from of the brain mitochondria.

Effects of Simulated Heat Wave and Ozone on High Fat Diet ApoE Deficient Mice

Objective To discuss the cardiac toxicities of a heat waves and ozone exposure on cardiovascular diseases（CVDs） and explore a possible mechanism. Methods The incidence of ozone exposure combined with heat wave was simulated in the Shanghai Meteorological and Environmental Animal Exposure System（Shanghai-METAS）. A total of 64 Apo E-/-mice, matched by weight, were randomly divided into 8 groups and exposed to heat wave conditions or ozone. The levels of creatine kinase（CK）, D-lactate dehydrogenase（D-LDH）, intercellular adhesion molecule 1（sICAM-1）, tumor necrosis factor alpha（TNF-α）, nitric oxide（NO）, endothelin-1（ET-1）, D-dimer（D2 D）, plasminogen activator inhibitor-1（PAI-1） and blood lipid in plasma and heat shock protein-60（HSP60）, hypoxia inducible factor 1 alpha（HIF-1α）, interleukin-6（IL-6）, C-reactive protein（CRP）, superoxide dismutase（SOD）, and malondialdehyde（MDA） in hearts were measured after exposure. Results The levels of all indicators, except for SOD, increased with the ozone-only exposure. However, cardiac damage was most significant when the heat wave conditions were combined with severe ozone exposure. Moreover, the levels of CK, D-LDH, NO, PAI-1, sICAM-1, and TNF-α in plasma increased significantly（P 〈 0.05）, and the contents of HSP60, HIF-1α, CRP, and MDA in hearts increased considerably（P 〈 0.05）, but the activity of SOD decreased significantly. In addition, the levels of four blood lipid items remarkably increased（except the level of HDL-C which decreased significantly） with ozone exposure. Conclusion A short-term exposure to a heat wave and ozone causes severe toxic effects on the heart. Cardiac damage was most significant under combined heat wave and severe ozone exposure simulations.

Influences of Chloropazine, Nimodipine and Their Combination on the Toxic Effects of Cadmium in Liver and Kidney of Mice

The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A seties of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2+ AT-Pase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination l h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that Crs could protect kidney tissue against Cd-induced damage, as the urinary γ-glutamyl traspepti dase (γ- GT ) and N- acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of Crs and NIMO.Both CPZ and NIMO showed a considerable protective effect against the deerease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significanily by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO consideraby increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.

The microstructural effects of aqueous extract of Garcinia kola(Linn) on the hippocampus and cerebellum of malnourished mice

Objective:To assess the neuroprotective effects of aqueous extract of Garcinia kola on neurotoxin administered malnourished mice adopting histological procedure.Methods:The study was carried out using thirty-two adult malnourished mice which were randomly assigned into four groups(n=8):A,B,C and D.Group A served as control,while the other groups served as the experimental groups.Animals in group A were fed malnourished diet ad libitum and given water liberally.Animals in group B were administered with 3-Nitropropionic acid(3-NP)(neurotoxin)only at 20 rag/kg body weight,group C were given only Garcinia kola extracts,and group D were pre-treated with Garcinia kola extracts at 200 mg/kg for seven days prior to administration of neurotoxin at 20 mg/kg body weight.After three days of neurotoxins administration in the relevant groups,the brains were excised and fixed in formal calcium for histological processing.Results:The study showed that hippocampal and cerebellar neurons of animals in group B exhibited some cellular degeneration and blood vessel blockage,which were not seen in groups A,C and D.Cresyl violet staining was least intense in group B than in groups A,C and D.Despite the fact that animals in group D has equal administration of 3-Nitropropionic acid concentration,there were no traces of neural degeneration as it was evidenced in group B.Conclusions:It is concluded that Garcinia kola has protective effects on the neurons of the hippocampus and cerebellum of malnourished mice.

Avidin chase reduces side effects of radioimmunotherapy in nude mice bearing human colon carcinoma

AIM: To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.METHODS: Purified anti-CEA monoclonal antibody (McAb)was biotinylated with NHS-biotin, and then radiolabeled with 188Re by the direct method. 188Re-labeledbiotinylated anti-CEA McAb (188Re-CEA McAb-Bt) was intravenously injected followed by intravenous injection of avidin after 24 h. SPECT imaging and biodistribution study were performed at 28-48 h after the injection of 188Re-CEA McAb-Bt. Three groups of nude mice subcutaneously grafted with human colon carcinoma were treated 7 d after the graft. Mice in the avidin chase group received intravenous injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg) followed by intravenous injection of cold avidin (80 μg) after 24 h. Mice in the control group (treated group without avidin chase) only received the injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg), another control group (non-treated group) only received 0.1 mL normal saline solution. Toxicity was evaluated on the basis of change of body weight and peripheral WBC counts, and therapy effects were determined by variation in tumor volume. Histological analysis of tumors was also performed.RESULTS: Avidin chase markedly accelerated the clearance of 188Re-CEA McAb-Bt from the blood and normal tissues. The tumor uptakes of 188Re-CEA Mc Ab-Bt at 28 h were 5.90 and 6.42% ID/g, respectively, in chase group and in non-chase group, while the tumor-to-background (T/NT) ratios were 3.19 and 0.56, respectively. The tumor uptake was slightly decreased by avidin chase, but the T/NT ratios were increased. In treated groups the growth rate of body weight and the number of WBC decreased after injection of 188Re-CEA McAb-Bt, and the WBC counts recovered earlier in the group with avidin chase than in the group without avidin chase. Compared to the nontreated group, treated groups with and without avidin chase showed significant anti-tumor effects.CONCLUSION: Avidin chase can effectively reduce the side effects of RIT, and improve therapeutic efficacy.

Analgesic and Anti-Inflammatory Effects of Herbal Mixture Extracts in Mice

Herbal mixture extracts (HME) comprised of Semen Sojae Nigrum, Fructus Cnidii, Radix Glycyrrhizae, and Cornu Cervi. Herein, we employed three mouse models, including hot-plate test, acetic acid (AA)-induced writhing test and AA-induced vascular permeability test, to determine analgesic and anti-inflammatory effects of HME. Results revealed that HME exhibited analgesic effects in hot-plate test and in AA-induced writhing test, as evidenced by increasing the latency to lick paws and decreasing AA-induced writhing counts, respectively. HME also significantly and dose-dependently decreased AA-induced vascular permeability, indicating HME exhibited anti-inflammatory effects. Similar improvement can be observed in aspirin treatment that used as positive control in this study. Most of medicinal effects of Fructus Cnidii are considered to attribute to coumarins, such as osthol (OST) and imperatorin (IMP) with several pharmacological activities. We then used OST and IMP as bioactive components in HME. The content of OST and IMP in HME was 3.57 ± 0.10 mg/g and 1.20 ± 0.02 mg/g, respectively, from three independent batches. Only OST possessed inhibitory effects in three mouse models, suggesting that OST may partially involve in protective effects of HME. These results demonstrated that HME has a potential on anti-analgesic effects and anti-inflammatory actions.

Effects of Omethoate on Liver Insulin Signaling in Mice

According to the report of the International Diabetes Federation, there were 382 million people affected with diabetes in 2013 and it is expected that this number will increase to 592 million by the year 2035;. Diabetes is caused due to the interaction between environmental and genetic factors;.

ANTITUMOR EFFECTS OF WICK OF SUN-FLOWER STEM IN MICE

A well-known Chinese traditional drug, decoction of wick of sun-flower stem, has been used to treat cancer and certain other diseases.1,2 Animal experiments in mice showed that transplantation of Sarcoma 180 (S180) and of Uterus cervical cancer 14 (U14) were signlflcanly inhibited by this decoction. The Inhibition rates of tumor weight were 33 -81 % and in about 6 - 20% of treated mice, complete tumor regression has been demonstrated. So tar no acute toxic side-effect was noted. This is in contrast to most of the antitumor chemltherapeutic drugs known to produce different degrees of toxlcity or induce Immunosuppression as a side effect. For this reason, we have undertaken the present study.

A STUDY OF THE RADIOSENSITIVE EFFECTS ON MAMMARY CARCINOMA IN MICE BY CHINESE MEDICINE (SALVIA PLUS ASTRAGALUS) AND ASPIRIN

The effect of treatment with Chinese medicine including Salvia miltiorrhizan and Astragalus, and the nonsteroid anti-inflammatory drug aspirin alone or combining radiotherapy, was investigated in 6-8 week-old TA2 mice being inoculated mammary carcinoma. The date indicated the following conclusions: the tumor growth could be inhibited by aspirin alone (p<0.01) but Chinese medicine group was observed. Mice treated with radiotherapy together with medicine both Chinese medicine and aspirin, had a statistically significant tumor inhibiting (p<0.01) as compared to mice treated with radiotherapy alone. The function to prevent the normal tissues from radiation by these two medicine groups were observed simultaneously. In addition, blood-flow volume of microcirculation, immune function and lymphocyte micronucleus were examined, which were used to analyse potential mechanism of sensitizing enhancement for Chinese medicine and aspirin.

Effects of Langchuangjing Granule (狼疮净冲剂) on Apoptotic of CD_4^+T and CD_(19)^+B in Spleen of BXSB Mice with Systemic Lupus Erythematosus

Objective: To study the effect on apoptosis of CD 4 +T、CD 19 +B in spleen of BXSB mice with systemic lupus erythematosus treated with Langchuangjing Granule (LCJG, and to probe into the mechanism of the tr eatment. Methods: The apoptosis was examined by the flow cytometric analysis and immunofluorescence double-staining method. Results: Apoptosis of male BXSB mice speeds up. LCJG can restrain the excessive apoptosis of CD 4 +T and CD 19 +B cells in spleen. Conclusion: LCJG treated systemic lupus erythematosus by restraining the excessive apoptosis of T, B lymphocytes, probably restraining the release of excessive amount of apoptotic DNA fragments, so decreasing abnormal proliferation of B cells and the produce of autoantibodies.

EFFECTS OF PSEUDOFYPE RETROVIRUS CONTAINING HUMAN N-RAS ANTISENSE GENE ON THE GROWTH OF HUMAN LIVER CANCER LTNM4 TRANSPLANTED IN NUDE MICE

An amphotropic pseudotype retrovirus containing human N-ras antisense gene was constructed and packaged with helper cells. It has been previously demonstrated that the virus did inhibit the growth of human hepatocarcinoma cell line PLC PRF/5 in vitro accompanied with the blockage of p21 expression. Based on these results, further study was carried on to examine the effect of these viruses on the growth of human hepatoma transplanted LTNM4 in nude mice. It has been shown that the retrovirus containing human antisense N-ras gene could inhibit the hepatoma in nude mice at a rate of 78% (P<0.05) as compared with saline control. No inhibition was observed in group treated with retrovirus which contained no N-ras sequence. These results in vivo lend further support that human N-ras antisense gene mediated by retrovirus could block the expression of the relevant oncogene and lead to the inhibition of cancer growth. It also provided the basis for further approaches of gene therapy for human cancer.

Immunoregulatory Effects of Nuhuang Fuzheng Granules on Mice with Cytoxan-induced Immunosuppression

[Objectives]To study immunoregulatory effects of Nuhuang Fuzheng Granules on mice with Cytoxan-induced immunosuppression.[Methods]Kunming variety mice were randomly divided into the control group,model group,positive medicine group,and low,medium,and high dosage groups of Nuhuang Fuzheng Granules. Except the control group,the rest groups of mice were injected with Cytoxan at60 mg/kg to reproduce the immunosuppressive mice model,and were fed through stomach at 0. 5g/kg,1. 0 g/kg and 2. 0 g/kg Nuhuang Fuzheng Granules for seven days( twice a day); the positive control group was fed with Astragalus Polysacharin( 500 mg/L). The carbon clearance index,immune organ index,serum hemolysin were determined. IL-2,IFN-γ,and IL-4 levels in mouse serum were measured by ELISA. [Results] Nuhuang Fuzheng Granules could significantly incease the carbon granular expurgation index of mice with Cytoxan-induced immunosuppression,and the 2. 0 g/kg and 1. 0 g/kg dosage groups had better effect than 0. 5 g/kg dosage group( P < 0. 05); the spleen index of mice with Cytoxan-induced immunosuppression increased significantly and there was dose-effect relationship in a certain range of concentration; the thymus index and serum hemolysin HC_(50) were significantly higher than 0. 5 g/kg dosage group( P < 0. 05); IL-4 and IFN-γ in the serum was significantly higher than the model group( P < 0. 01),the increase of IL-2 was not significantly( P > 0. 05). [Conclusions] Nuhuang Fuzheng Granules can promote growth of immune organs and secretion of cytokines through improving the carbon granular expurgation ability of mice with Cytoxan-induced immunosuppression.

Growth-Promoting Effects of Liposome-Encapsulated Porcine Somatotropin in Mice

[Objective] To study growth-promoting effects of liposome-encapsulated porcine somatotropin (pST) and its sustained-release effects in mice. [Method] The mice were randomly divided into experimental groups and control group. The mice in the experimental groups were respectively administrated with pST and liposome-encapsulated pST via intraperitoneal injection, and those in the control group were administrated with saline. They were weighed on Day 7, 14 and 28, and the growth rate was calculated. [Result] The growth of mice had significant difference between the experiment groups and control group (P < 0.05), which indicated that the pST and liposome-encapsulated pST had growth-promoting effects in mice, and the liposome-encapsulated pST had sustained-release effects. [Conclusion] The liposome-encapsulated pST can promote the growth of animal and its sustained-release period is 7 d.

Immunotherapeutic effects of dendiritic cells vaccine pulsed with tumor cell lysate in mice with pancreatic carcinoma

Objective To observe the immunotherapeutic effects of dendritic cells vaccine pulsed with tumor cell lystate on mice with pancreatic carcinoma. Methods Dendritic cells (MTSC4) were pulsed with tumor cells lysate. The immune preventative and immnotherapeutic effects of DC vaccines on mice with pancreatic carcinoma were assessed. Results After vaccination of the DC vaccines,mice remained tumor-free for at least 25 days in DCs vaccines group,but in other groups the subcutaneous implantation tumorigenesis were found beginning 3 to 9 days. CTL stimulated by DC vaccines effected cytolytic activity against pancreatic carcinoma cells. The survival period was obviously prolonged in DCs vaccines group (56 ±9)d than in other groups P【0.01) and tumors (1.4 ±0.8)g in DCs vaccines group were significantly smaller than that in other groups (P 【 0. 05). Conclusion Tumor cell lysate-pulsed dendrtic cells vaccines can induce a specific and effective immune response against pancreatic carcinoma cell implanted in mice.

Radioprotective effects of the expression of FLT3 ligand regulated by Egr-1 regulated element on radiation injury of SCID mice

Objective: In order to explore the radioprotective effects of the expression of hematopoietic growth factors regulated by radio-inducible promoter on radiation injury. Methods:The human FL (Flt3 ligand) cDNA and EGFP (enhanced green fluorescent protein) cDNA were linked together with IRES and then inserted into the eukaryotic expression vector pCI-Egr, which was constructed by substituting CMV promoter in pCIneo with the Egr-1 promoter (Egr-EF). The vector was transferred into human bone marrow stromal ...

Lipid-lowering effect of Oroxylum indicum(L.)Kurz extract in hyperlipidemic mice

Objective:To investigate the effect of Oroxylum indicum fruit extract on high-fat diet-induced hyperlipidemic mice.Methods:The phytochemical composition of Oroxylum indicum fruit extract was determined by liquid chromatographymass spectrometry/mass spectrometry(LC-MS/MS)and gas chromatography-mass spectrometry.Forty-two male mice were used.The mice were divided into six groups:normal control,high-fat diet control,simvastatin treatment(20 mg/kg BW/day),and Oroxylum indicum fruit extract(100,200,300 mg/kg BW/day)treatment groups.Food intake,body weight,serum parameters,lipid profile,and histopathological lesions of the kidney,liver,and epididymal fat were observed.Results:LC-MS/MS results revealed four major components of Oroxylum indicum fruit extract:luteolin,apigenin,baicalein,and oroxylin A.Twenty-seven volatile oils were identified from Oroxylum indicum fruit extract.Daily oral administration of Oroxylum indicum fruit extract at 100 to 300 mg/kg BW/day significantly reduced the body weight,total cholesterol,triglyceride,and low-density lipoprotein cholesterol level(P<0.05),whereas high-density lipoprotein cholesterol was higher than the high-fat diet control group.Treatment with 300 mg/kg BW/day Oroxylum indicum fruit extract reduced the pathological lesion and prevented fat accumulation in the kidney and liver.Conclusions:Oroxylum indicum fruit extract has hypolipidemic effect in hyperlipidemic mice,and the active ingredients of Oroxylum indicum fruit extract,both flavonoids and volatile oils,should be further explored as an antihyperlipidemic agent.

Anti-Nociceptive Effect in Mice of Thillai Flavonoid Rutin

We investigated the anti-nociceptive effect of Excoecorio ogollocho （E.ogollocho） against chemically and thermally induced nociception, Albino mice received a dose of 10, 15, 20, or 25 mg/kg of alkaline chloroform fraction （Alk-CF） of E.ogollocho by oral administration. Compared with controls, AIk-CF decreased the writhing numbers （P〈0.01） in a dose dependent manner. Further we determined that, AIk-CF contained, a potent compared to control, also potent anti-nociceptive agent that acted via opioid receptors and using HPLC, identified this compound as Rutin. Docking simulation demonstrated that Rutin interacted strongly with cyclooxygenase, forming a number of specific hydrogen bonds. In conclusion we have identified peripheral and central anti-nociceptive activities of E.ogollocho that involve opioid receptor, and in which the active compound is Rutin.

Protective Effect of Mulberry Extract against Pb-induced Learning and Memory Deficits in Mice

Lead （Pb） is ubiquitous in the environment, and low-level Pb exposure can cause neurotoxicity and irreversible damage to children＇s cognition, learning and memory ability. Nutritional intervention is an effective method to prevent Pb poisoning. Mul- berry is rich in anthocyanins, possessing protective effects for nerves. This study investigated the neuroprotective effects of mulberry extract （ME） against Pb-induced learning and memory deficits in mice. The results showed that the learning and memory abilities of mice, assessed using the Morris test, improved significantly after treatment with ME at a dose of 100 mg/kg body weight. The level of Pb in the brains of mice in the three ME intervention groups decreased significantly, while NO production and anti-oxidant enzymes were significantly restored. It is suggested that ME inhibits Pb-induced neurotoxicity by reversing Pb-induced alterations in the aspect of neurotoxic effects and improving learning and memory.