DT-13, a saponin of dwarf lilyturf tuber,exhibits anti-cancer activity by down-regulating C-C chemokine receptor type 5 and vascular endothelial growth factor in MDA-MB-435 cells简

AIM： To investigate the anticancer activity of DT-13 under normoxia and determine the underlying mechanisms of action. METHODS： MDA-MB-435 cell proliferation, migration, and adhesion were performed to assess the anticancer activity of DT-13, a saponin from Ophiopogonjaponicus, in vitro. In addition, the effects of DT-13 on tumor growth and metastasis in vivo were evaluated by orthotopic implantation of MDA-MB-435 cells into nude mice; mRNA levels of vascular endothelial growth factor （VEGF）, C-C chemokine receptor type 5 （CCR5） and hypoxia-inducible factor 1a （HIF-1a） were evaluated by real-time quantitative PCR; and CCR5 protein levels were detected by Western blot assay. RESULTS： At 0.01 to 1 umol·L -1, DT-13 inhibited MDA-MB-435 cell proliferation, migration, and adhesion significantly in vitro. DT-13 reduced VEGF and CCR5 mRNAs, and decreased CCR5 protein expression by down-regulating HIF-1 a. In addition, DT-13 inhibited MDA-MB-435 cell lung metastasis, and restricted tumor growth slightly in vivo. CONCLUSION： DT-13 inhibited MDA-MB-435 cell proliferation, adhesion, and migration in vitro, and lung metastasis in vivo by reducing VEGF, CCR5, and HIF-la expression.     

Effect of dexamethasone injection into Zusanli(ST 36) acupoint on ovalbumin-induced allergic rhinitis

OBJECTIVE:To investigate the effects of acupunc ture with dexamethasone(A.Dex)on allergic rhini tis(AR)by injecting dexamethasone into the Zusan li(ST 36)acupoint.METHODS:Thirty 6-week-old female BALB/c mice were sensitized on days 1,5,and 14 by intraperitoneal injection of 100 pg of ovalbumin(OVA).The mice were then randomly divided into six groups(n =5 in each group).Five groups were sensitized intranasally with 2μL of 1.5 mg of OVA for 10 consecutive days,while one group was sensitized intranasally with PBS in a similar manner as a negative control group.One hour before each administration of intranasal OVA,two groups were orally administered either a control vehicle(distilled water;AR control group)or 200 pg/kg Dex(O.Dex group),while three groups received A.Dex at Zusanli(ST36)with Dex concentrations of 2,20,and 200μg/kg for each group,respectively.AR symptoms were evaluated by measuring the rubbing score,which comprised the number of nose,ear,and eye rubs that occurred in the initial 10 min after OVA intranasal provocation on the 10 th day.We isolated spleen,serum,and nasal mucosal tissue after measuring the rubbing score.Spleen weight was measured using an electronic microbalance.The levels of IgE,thymic stromal lymphopoietin,tumor necrosis factor-a,intercellular adhesion molecule-1,and macrophage-inflammatory protein-2 in serum or nasal mucosal tissue were measured using enzyme-linked immunosorbent assays.The serum histamine levels of OVA-sensitized AR mice were measured using O-phthaldialdehyde spectrofluorometry.Western blot analysis was performed on nasal mucosal tissue extracts.RESULTS:A.Dex significantly reduced the rubbing score,spleen weight,serum IgE,and serum histamine in OVA-sensitized mice.A.Dex significantly decreased the serum levels of inflammatory cytokines(thymic stromal lymphopoietin and tumor necrosis factor-a)in OVA-sensitized mice.A.Dex significantly reduced the nasal mucosal levels of inflammatory markers(intercellular adhesion molecule-land macrophage-inflammatory protein-2)in AR mice.A.Dex effectively attenuated the expression of caspase-1 and receptorinteractingprotein-2 in nasal mucosal tissue.CONCLUSION:A.Dex may be a new and useful therapy for AR.     

Anticancer Effects of Zaoxiu Compound Decoction on H22 Mice with Heps

Objective To investigate the anticancer effects of the Zaoxiu Compound Decoction(ZCD) on H22 mice with Heps and the influence on the construction of H22 cells. Methods With in vivo techniques, the antineoplastic drugs were given to hepatoma H22 model mice which were randomly divided into negative control(physiological saline), positive control(cyclophosphamide), high- and low-dose ZCD groups. After 10-d administration, the pathological examinations of tumor tissue, livers, and kidneys in mice were carried out and the inhibitory rate on tumor was calculated. Results The high-and low-dose ZCD had obvious inhibition on H22 cells. The pathological observation showed that high- and low-dose ZCD had a strong inhibitory effect on H22 cells as well as positive control, with few toxic effects to the livers and kidneys in mice. Conclusion ZCD has the anticancer effect and has no obvious toxic effects on the model mice.     

Effects of Qingguang'an(青光安)containing serum on the expres-sion levels of autophagy-related genes in human Tenon's fibro-blasts induced by transforming growth factor beta 1

OBJECTIVE:To explore the effects of Qing-guang'an(青光安)containing serum on the expres-sion levels of autophagy related genes in the trans-forming growth factor b...     

Effect of curcumin on rats/mice with diabetic nephropathy： a systematic review and Meta-analysis of randomized controlled trials

OBJECTIVE： To assess the renal protective effects of curcumin administration ondiabetic rats/mice.METHODS： Databases were searched electronically and conference papers searched manually for search terms to find relevant studies. Articles were assessed independently by two reviewers. Review Manager 5.1 was used fordata analysis.RESULTS： Fourteen randomized controlled experiments were included. Meta-analysis demonstrated that blood sugar levels and kidney weight to body weight ratios in the model group were higher than those in the normal group, and the curcumin group had significantly lower mesangial area to glomerular area ratios compared with the model group, and also lower levels of urinary protein,blood urea nitrogen and serum creatinine.CONCLUSION： Curcumin shows protective effects on the kidneys of rats/mice with diabetes.     

Anti-asthma effects of synthetic salidroside through regulation of Th1/Th2 balance

AIM： The aim of the study was to investigate the effect and mechanism of action of synthetic salidroside in an ovalbumin （OVA）-induced asthma model in mice. METHOD： BALB/c mice were sensitized with an intraperitoneal injection of ovalbumin （OVA） to induce a mouse model of asthma in paracmasis. The mice were treated with dexamethasone as the positive control. At the end of the study, respiratory reactivity was detected, the numbers of various kinds of white blood cells in the bronchoalveolar lavage fluid （BALF） were counted, and the levels of IL-4 and INF-γ in BALF were determined. Quantitative PCR was used to detect the mRNA contents of IL-4 and INF-γ in lung tissue. Histologic examination was performed to observe inflammatory cellular infiltration. RESULTS： Salidroside treatment virtually eliminated airway hyper-reactivity, markedly reduced the eosinophil percent, obviously reduced the levels of IL-4 and raised INF-γ in the bronchoalveolar lavage fluid （BALF） compared with the sham-treated group. Quantitative PCR on the mRNA content of IL-4 and INF-γ provided confirmation. Lung histologic observations showed that salidroside reduced inflammation and edema. These effects were equivalent to the effects of dexamethasone. CONCLUSION： Synthetic salidroside exhibits an anti-asthma effect which is related to the regulation of Th1/Th2 balance. This provides a new possibility for treatment of allergic asthma.     

Sedative and hypnotic effect of freeze-dried paeoniflorin and Sini San freeze-dried powder in pentobarbital sodium-induced mice

OBJECTIVE： To investigate the sedative and hyp- notic activity of paeoniflorin and freeze-dried Sini San powder on mice and provide a reliable method for determining the pharmacodynamic material ba- sis of Sini San. METHODS： Male adult mice weighing 20-22 g were used in this study. Three experiments were carried out. Synergism with pentobarbital was used as an index for hypnotic effect. Loss of the righting reflex was used to determine the start of sleep. Sleep latency and sleeping time were recorded in each experiment. RESULTS： The coefficient of variation of the suprathreshold dose （55 mg/kg） was significantly lower than that of the threshold dose. The sleep latency of mice was significantly decreased, and the sleep- ing time of mice was significantly prolonged. The effects of paeoniflorin and Sini San on prolonging the sleeping time of mice induced by pentobarbital sodium were significantly stronger than those in the control group. CONCLUSION： Paeoniflorin produces significant sedative and hypnotic effects, and there is an obvi- ous dose-effect relationship.     

Pretreatment with Jieduxiezhuo decoction impedes elevations in se- rum uric acid levels in mice

OBJECTIVE： To investigate whether Jieduxiezhuo decoction （JDXZD） can prevent serum uric acid ele- vations in mice. METHODS： Hyperuricemia in mice was induced by intraperitoneally administering uric acid （250 mg/ kg）. Concentrations of uric acid in serum were de- termined using the uric acid enzyme method. Mice were treated with JDXZD for 4 days before uric acid was administered. RESULTS： After intraperitoneal injection of uric ac- id, serum uric acid concentrations in mice signifi- cantly increased. However, the levels of uric acid in groups pretreated with 16.25 or 4.06 g/kg of JDXZD were significantly lower than those in the model and normal groups. CONCLUSION： Pretreatment with JDXZD slowed in- creases in serum uric acid levels in mice intraperito-neally administered uric acid.     

Puerarin affects bone biomarkers in the serum of rats with intrauterine growth restriction

OBJECTIVE:To investigate serum bone biomarkers in rats with intrauterine growth restriction(IUGR)in order to determine the effects of puerarin on bone metabolism.METHODS:A rat model of IUGR was induced using a low protein diet during pregnancy.The offspring were given puerarin or an identical volume of saline via subcutaneous abdominal injection.All rats were studied at 1,3,and 8 weeks of age.Serum biomarkers of bone formation,including insulin-like growth factor-1(IGF-1),bone-specific alkaline phosphatase(BALP),osteocalcin(OC),osteoprotegerin(OPG),receptor-activator of nuclear factor-κB ligand(RANKL),as well as blood levels of calcium and phosphorus were measured.RESULTS:Serum BALP,OPG,IGF-1,and OC levels,as well as the OPG/RANKL ratio,were lower in the IUGR group compared with the control group at 1week of age(P=0.024,0.011,0.014,0.004,and0.002,respectively).At 3 weeks of age,the serum BALP and OC levels were higher in the protein-re-stricted group compared with the control group(P=0.003 and 0.001,respectively).A comparison between the IUGR plus puerarin intervention group and the IUGR group revealed differences in the levels of BALP and IGF-1 at 3 weeks of age(P=0.008 and 0.003,respectively).In addition,serum OPG and OC levels and the OPG/RANKL ratio were higher at 8 weeks of age(P=0.044,0.007,and0.016,respectively).No differences in serum calcium and phosphorus levels were observed among the three groups.CONCLUSION:Our study demonstrates that the bone microenvironment of the fetus can be altered by a low protein maternal diet and that puerarin can reverse these effects.These results indicate that the nutritional environment plays an important role in early skeletal development and that the bone turnover of IUGR rats can be altered by puerarin treatment.     

Hepatoprotective Effects of Yintian Granule on Experimental Liver Injury in Mice

Objective Yintian Granule (YTG), as a type of local preparation and applied for Chinese patent, is mainly composed of several traditional Chinese herbs used as both drug and food such as Lonicera macranthoides, Gardenia jasminoides, and Asparagus cochinchinenis, and has been reported to demonstrate the beneficial effects on human health in other researches. In this paper, the protective effects of YTG against experimental acute liver injury of mice were investigated to assess the value of this innovative Chinese herbal compound. Methods Carbon tetrachloride (CCl4) and 50% ethanol were used respectively to induce the acute liver injury model in mice pre- administered with YTG. Lai’s method was used to detect the level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, Coomassie brilliant blue method was used for the determination of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, and hematoxylin-eosin (HE) staining was used for the observation of liver histomorphometry. Results YTG significantly lowered the elevated ALT and AST levels, increased the SOD activity, decreased the MDA content, and inhibited the deterioration of liver. Conclusion YTG exerts protective effected against hepatocyte damage in mice induced by CCl4 and 50% ethanol, respectively.     

Anticancer activity of Sargassum wightii Greville on Dalton’s ascitic lymphoma简

AIM： Sargassum wightii Greville is a marine brown alga belonging to the Sargassaceae family which has about 200 species. The ethanolic extract of the whole dry plant powder contained numerous phytoconstituents, including flavonoids. The study was fo- cused on the anticancer activity ofSargassum wightii in mice. METHOD： The ethanolic extract ofSargassum wightii （EESW） at two dose levels was used to examine the anticancer activity in mice using DAL cell lines to induce cancer. The body weight, viable and non-viable tumor cell count, mean survival time, increase in life span, and hematological parameters were observed for anticancer activity of EESW. RESULTS： The intraperitoneal inoculation of DAL cells in mice significantly increased cancer cell count. The decrease in the cancer cell number observed in the EESW-treated group cancer animals indicates that the test drug has a significant inhibitory ef- fect on the tumor cell proliferation. Treatment with EESW also showed a significant decrease in tumor weight, and hence increased the lifespan of DAL-treated mice. In addition, EESW administration significantly restored the hematological parameters in DAL-treated mice. CONCLUSION： The present study results suggest that administration of extract offers enhanced antioxidant potential. Therefore it can be concluded from this study that EESW possesses anticancer activity.     

Oral JS-38,a metabolite from Xenorhabdus sp.,has both anti-tumor activity and the ability to elevate peripheral neutrophils

AIM： JS-38（mitothiolore）, a synthetic version of a metabolite isolated from Xenorhabdus sp., was evaluated for its anti-tumor and white blood cell（WBC） elevating activities. METHOD： These anti-proliferative activities were assessed in vitro using a panel of ten cell lines. The anti-tumor activities were tested in vivo using B16 allograft mouse models and xenograft models of A549 human lung carcinoma and QGY human hepatoma in nude mice. The anti-tumor interactions of JS-38 and cyclophosphamide（CTX） or 5-fluorouracil（5-Fu） were studied in a S180 sarcoma model in ICR mice. Specific stimulatory effects were determined on peripheral neutrophils in normal and CTX- and 5-Fu-induced neutropenic mice. RESULTS： The IC50 values ranged from 0.1 to 2.0 μmol·L-1. JS-38（1 μmol·L-1） caused an increase in A549 tumor cell apoptosis. Multi-daily gavage of JS-38（15, 30, and 60 mg？kg-1？d-1） inhibited in vivo tumor progression without a significant effect on body weight. JS-38 additively enhanced the in vivo anti-tumor effects of CTX or 5-Fu. JS-38 increased peripheral neutrophil counts and neutrophil rates in normal BALB/c mice almost as effectively as granulocyte colony-stimulating factor（G-CSF）. In mice with neutropenia induced by CTX or 5-Fu, JS-38 rapidly restored neutrophil counts. CONCLUSION： These results suggest that JS-38 has anti-tumor activity, and also has the ability to increase peripheral blood neutrophils.     

Effect of Runing II on the Growth and Metastasis of Transplanted Tumor in Mammary Cancer-bearing Mice and Its Mechanism

Objective： To study the effect of Runing II （a Chinese herbal preparation for mammary cancer） on the growth and metastasis of transplanted tumor of mammary cancer MA-891-bearing TA2 mice and its mechanism. Methods： The model of mammary cancer MA-891 cell strain transplanted tumor of TA2 mice with lung metastasis were developed to observe the effect of Runing II on the growth and metastasis of the transplanted tumor. The immunohistochemical method and image analysis were adopted to detect the levels of vascular endothelial growth factor （VEGF）, vascular endothelial growth factor receptor （VEGFR）, and micro-vessel count （MVC） and micro-vessel area （MVA）. Results： In the Runing II group, the tumor weight inhibition rate and the lung metastasis inhibition rate were 37.3% and 65.4% respectively, the tumor growth and lung metastasis were obviously inhibited; And the levels of VEGF and VEGFR, MVC and MVA were significantly decreased as compared with those in the tumor-bearing control group （P〈0.05）. Conclusion： The Chinese herbal preparation Running II can inhibit the metastasis of tumor through inhibiting the angiogenesis, and the mechanism is possibly related with down-regulation of VEGF and VEGFR expression.     

Berberine reverses LPS-induced repression of CYP7A1 through an anti-inflammatory effect

Objective: To evaluate the anti-inflammatory effect of berberine(BBR) on the lipopolysaccharide(LPS)-induced acute phase response and its modulation of the altered bile acid metabolism induced by LPS treatment.Methods: An acute phase response was induced by intraperitoneal injection of LPS(5 mg/kg, ip) in C57 BL/6 J mice, and the BBR treatment group was orally administered with BBR(200 mg/ky, ig). The levels of TNFα, IL-1β and IL-6 in the serum were measured using an ELISA kit, and their expression levels in the liver were measured using q RT-PCR. The bile acid pool was measured using a commercial bile acid kit, and the expression levels of enzymes involved in bile acid metabolism were measured by q RTPCR. The expression levels of CYP7 A1, p65 NF-κ B and the MAPK signaling pathway was measured using Western blotting.Results: LPS treatment suppressed the expression of CYP7 A1 and CYP8 B1, and the total bile acid pool was also reduced. Pretreatment with BBR inhibited the pro-inflammatory biomarkers TNFα and IL-1β in the serum, as well as the expression of TNFα, IL-1β and i NOS mRNA in the liver. BBR treatment did not affect the reduction in the bile acid pool size induced by LPS, but significantly increased the concentration of bile acids in the liver, which was consistent with the upregulated expression of CYP7 A1 and CYP8 B1. The MAPK signaling pathway was activated by BBR treatment, while the p65 NF-κ B signaling pathway was inhibited.Conclusion: BBR can offer an anti-inflammatory effect and reverse the inhibition of CYP7 A1 and CYP8 B1 expression caused by LPS treatment, as well as induce the production of bile acids in liver, probably via MAPK signaling; However, treatment with BBR had no effect on the size of total bile acid pool.     

Taxifolin attenuates inflammation via suppressing MAPK signal pathway in vitro and in silico analysis

Objective Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS)were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.     

Immunological Effects of Total Flavones from Leaves of Choerospondias axillaris on Mice

Objective To investigate the effect of total flavones from the leaves of Choerospondias axillaris(TFLCA) on the immune function of normal mice and to provide the experimental basis for the reasonable application of C. axillaris.Methods The carbon clearance method, cutaneous delayed hypersensitivity reaction method, serum hemolysin method, and index of immune organs were used to study the effect of TFLCA on the immune function of mice. Results TFLCA could enhance the phagocytic function of mononuclear macrophage and the cutaneous delayed hypersensitivity reaction of mice, and increase the content of hemolysin antibody and the thymus index in mice.Conclusion TFLCA could improve the celiac macrophage activity and specific immunity of mice, and TFLCA,consisting with the total flavones of Choerospondiatis Fructus(TFCF), has the effect on the immune function of mice.So both TFLCA and TFCF have the regulatory effects on the immune function of mice.     

Effects of the Aidi Dripping Pills on Immune Functions of the Tumor-bearing Mouse

Objective： To study the effects of Aidi Dripping Pills on immune functions of the tumor-bearing mouse on the basis of the previous experimental studies on its tumor-inhibiting and life-prolonging effects. Methods： By using the transplantation tumor mouse models, the effects of Aidi Dripping Pills on the lymphocyte transformation rate and the hemolysin formation in the Sis0 tumor-bearing mice, and on the phagocytic function of macrophages in the abdominal cavity of H22 tumor-bearing mice were investigated. Results： In the 2.25 g/kg and 1.125 g/kg Aidi Dripping Pills groups, the lymphocyte transformation rates in the Sis0 tumor-bearing mice were significantly higher than that of the control group （P〈0.01）. In all the Aidi Dripping Pills groups, HC50 significantly increased （P〈0.01 or P〈0.05）, carbon granular clearance significantly raised, and both the phagocytic index and phagocytic coefficient were significantly higher than those in the control group （P〈0.01 or P〈0.05）. Conclusion： The Aidi Dripping Pills can significantly increase the cellular immune function, the humoral immune function and the phagocytic function of the mononuclear- macrphages, so it may show anti-tumor effects by enhancing the function of the reticuloendothelial system.