Previous studies have shown that ginsenoside Rb1 (Rb1), one of active components in ginseng, can activate insulin signaling pathway and promote translocation of glucose transporters (GLUTs) to increase glucose uptake in adipocytes. However, the effect of Rb1 on the expressions of GLUTs remains unknown. In this study, the effects of Rb1 on GLUT1 and GLUT4 were observed in 3T3-L1 adipocytes and epididymal adipose tissue of db/db obese diabetic mice. Male db/db mice were treated with Rb1 by intraperitoneal injection at the dosage of 20 mg x kg(-1) for 14 d. Rb1 reduced HOMA-IR significantly (P < 0.05, n = 5), and FBG and FINS sowed declining trend after treatment with Rb1. Rb1 recovered the expressions of GLUT1 and GLUT4 and phosphorylation of AKT in adipose tissue of db/db mice. In vitro, glucose consumption in 3T3-L1 adipocytes treated with 10 micromol x L(-1) Rb1 for 24 h was elevated (P < 0.05, n=3), and mRNA of GLUT1 and GLUT4 were up-regulated (P < 0.05, n=3) and proteins of GLUT1 and GLUT4 were also increased. AKT was activated in adipocytes treated with Rb1 for 3 h. It can be concluded that ginsenoside Rb1 can up-regulate the expression of GLUTs in adipose tissue, in addition to activate insulin signalling pathway, which may partially account for its insulin sensitizing activity and regulating effect of glucose metabolism.
3T3 Cells ; Adipocytes ; drug effects ; Animals ; Cell Line ; Diabetes Mellitus, Experimental ; metabolism ; Ginsenosides ; pharmacology ; Glucose ; metabolism ; Glucose Transport Proteins, Facilitative ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Up-Regulation ; drug effects

Ginsenoside Rb1 is an active component in ginseng. Previous in vitro experiments showed that ginsenoside Rb1, could inhibit lipolysis and promote glucose transporter in adipocytes. This study focused on the effect of ginsenoside Rb1 in insulin resistance and ectopic fat deposit in obese mice induced by high fat diet and its molecular mechanism. Obese male C57/L mice induced by high fat diet were randomly divided into the diet-induced obesity group (DIO group), the ginsenoside Rb1 group (Rb1 group) and the rosiglitazone group (Rog group), and continuously fed with high fat diet. In addition, male C57/L mice fed with normal diet were selected as the normal group (NC group). Mice in Rb1 group and Rog groups were intraperitoneally injected with ginsenoside Rb1 and rosiglitazone with the dosage of 20 mg x kg(-1) and 10 mg x kg(-1), respectively. NC and DIO groups were intraperitoneally injected with the same amount of saline. Two weeks later, the intraperitoneal glucose tolerance test (IPGTT) was performed. Three days later, the mice were killed, and their serum samples were collected to detect insulin and free fatty acid (FFA). Their livers were weighed to examine the triglyceride content, and a pathological detection was performed. Epididymal adipose tissues were weighed, and PDE3B, HSL and perilipin were detected by Western blotting. The results showed that the treatment with ginsenoside Rb1 for two weeks could improve the glucose tolerance of obese mice. Except for 0-120 min, the areas under the glucose tolerance curve (0-30 min, 0-60 min and 0-90 min) in the Rb1 group were less than that in the DIO group (P < 0.05, n = 5), with a much lower HOMA-IR (P < 0.05, n = 5). The fat level of obese mice was significantly reduced by Rbl (P < 0.05, n = 5), and so were liver weight/weight (P < 0.05, n = 8). The increased serum FFA of obese mice declined after the treatment of Rb1 (P < 0.05, n = 8). Rb1 could partially recover the expression of perilipin in adipose tissues, but without obvious change in the expressions of PDE3B and HSL and the phosphorylated activation. The above findings indicated that ginsenoside Rb1 could reduce the release of FFA and alleviate the ectopic deposit of triglyceride by up-regulating the expression of perilipin in adipose tissue, which may be one of its mechanisms for improving the insulin resistance and abnormal glucose metabolism of organisms.
Adipose Tissue ; drug effects ; pathology ; Animals ; Body Weight ; drug effects ; Diet, High-Fat ; adverse effects ; Dose-Response Relationship, Drug ; Fatty Acids, Nonesterified ; blood ; Gene Expression Regulation ; drug effects ; Ginsenosides ; pharmacology ; Glucose Tolerance Test ; Insulin ; blood ; Insulin Resistance ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity ; blood ; etiology ; metabolism ; pathology ; Organ Size ; drug effects ; Triglycerides ; metabolism

3 cm)and small lesions(diameter≤3 cm)were 80.6%(79/98)and 67.2% (45/67),respectively(P

Objective To observe the effect of ginsenoside Rb1,the most abundant ginsenoside in ginseng root,on differentiation and lipolysis of 3T3-L1 cells and to explore its anti-diabetic mechanism.Methods 3T3-L1 preadipoeytes were induced under standard differentiation process in the presence of 0.1,1,10,100?mol/L ginsenoside Rb_1 for 6 days.Oil red O staining,measurement of triglyceride contents and glucose uptake assay were performed.The expressions of mRNA and protein of PPAR?2,C/EBP?,ap2,glucose transporter (Glut) 1,and Glut4 were analysed with quantitative real time-PCR and Western blot.The binding affinity of Rb_1 to PPAR?-LBD was evaluated by Surface Plasmon Resonance (SPR).Lipolysis of adipocytes was examined by the measurement of glycerol released from adipoeytes treated with Rb_1 for 1 h.Results Ginsenoside Rb_1 facilitated differentiation of 3T3-L1 preadipoeytes in a dose-depondent manner.10?mol/L ginsenoside Rb_1 increased lipid accumulation by about 56%.Treatment of differentiating adipocytes with 10?mol/L ginsenoside Rb_1 increased the expressions of PPAR?2 and C/EBP?mRNA and protein,as well as mRNA expression of ap2,one of their target genes.After treatment of differentiating adipoeytes with Rb_1,basal and insulin-mediated glucose transport augmented significantly accompanied by up-regulations of mRNA and protein level of Glut4,but not of Glutl.SPR showed Rb_1 could bind to PPAR?which suggested Rb_1 was a ligand of PPAR?.Ginsenoside Rb_1 inhibited basal lipolysis in adipoeytos in a dose-dependent manner.However,it did not affect isoproterenol-stimulated lipolysis.Conclusion As a PPAR?ligand,ginsenoside Rb_1 promotes adipogenesis,inhibitas basal lipolysis and inereasos basal and insulin-mediated glucose transport in cultured adipoeytes.Therefore,anti-diabetic and insulin-sensitizing activity of ginsenosides is,at least in part,involved in the enhancing effect on PPAR?2 and C/EBP?expressions,hence promoting adipogenesis and glucose uptake,and inhibiting lipolysis in adipocytes.

OBJECTIVETo investigate the proliferation-inhibiting and multidrug-resistant reversing effect of bortezomib on human HL-60 cells, and to explore the mechanism of bortezomib-induced proliferation inhibition in human leukemia cells.

METHODSThe multidrug resistant leukemia cell lines HL-60/DNR and HL-60/VCR cells were used as models, and sensitive HL-60 cells as a control. The cytotoxicity of bortezomib on HL-60, HL-60/DNR, HL-60/VCR cells were measured by MTT method, and the non-cytotoxicity dose was determined as reversible dose. The cells were divided into 4 experimental groups: HL-60/DNR + DNR, HL-60/DNR + DNR + bortezomib, HL-60/VCR + VCR, HL-60/VCR + VCR + bortezomib. The bortezomib resistant reversal fold was calculated. The levels of XIAP, cIAP-1, and cIAP-2 mRNA and proteins expression and the activation of NF-κB of the HL-60/DNR, HL-60/VCR cells were examined by quantitative real time RT-PCR and western blot respectively after treated with gradually increasing concentrations of bortezomib (10, 40, 80 nmol/L) for 48 hours.

RESULTSBortezomib inhibited the cell growth of HL-60, HL-60/DNR, and HL-60/VCR in a concentration-dependent manner. The IC(50) values were (28.90 ± 3.99), (81.19 ± 9.34), and (73.48 ± 8.94) nmol/L, respectively. After treated with 10nmol/L bortezomib for 48 hours, the IC(50) value of DNR to HL-60/DNR decreased from (12.90 ± 1.75) µmol/L to (3.54 ± 0.57) µmol/L (P < 0.01), and that of VCR to HL-60/VCR from (33.25 ± 7.28) µmol/L to (9.97 ± 1.15) µmol/L (P < 0.01). The reversal fold (RF) values were 3.32 ± 0.53 and 2.64 ± 0.28, respectively. Bortezomib down-regulated the levels of XIAP, cIAP-1, and cIAP-2 mRNA and protein expression and inhibited the NF-κB activation in a concentration-dependent manner.

CONCLUSIONBortezomib can inhibit the proliferation of HL-60 cells and reverse multidrug-resistance in the cells. The possible mechanism is associated with down-regulation of IAPs expression.

Boronic Acids ; pharmacology ; Bortezomib ; Cell Proliferation ; drug effects ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; HL-60 Cells ; Humans ; Leukemia ; genetics ; metabolism ; pathology ; NF-kappa B ; metabolism ; Pyrazines ; pharmacology ; RNA, Messenger ; genetics

OBJECTIVETo examine the extent of hypoxia in oral squamous cell carcinoma and investigate the factors related to the hypoxia.

METHODSAn animal model of oral squamous cell carcinoma was established and single photon emission computed tomography (SPECT) with 99mTc-HL91 used to detect the hypoxia extent of the oral squamous cell carcinoma. The expression of hypoxia inducible factor 1 alpha (HIF-1alpha) was examined by immunohistochemical staining in 42 cases of formalin-fixed paraffin-embed squamous cell carcinoma.

RESULTSThe uptake of 99mTc-HL91 in the tumor tissue was higher than that in normal tissue and had linear relation with the tumor size (P < 0.05). There was no HIF-1alpha expression in the normal oral mucosa. The expression of HIF-1alpha was high in oral mucosa carcinoma and closely related to the differentiation degree of tumor and metastasis of lymph node (P < 0.05).

CONCLUSIONSTumor tissue had broad hypoxic region. HIF-1alpha highly expressed in oral squamous cell carcinoma and may play an important role in carcinogenesis and aggression.

Adult ; Aged ; Aged, 80 and over ; Animals ; Carcinoma, Squamous Cell ; diagnostic imaging ; metabolism ; pathology ; Female ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Mouth Neoplasms ; diagnostic imaging ; metabolism ; pathology ; Pilot Projects ; Tomography, Emission-Computed, Single-Photon ; Xenograft Model Antitumor Assays

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Line, Tumor ; Humans ; Oxides ; pharmacology

OBJECTIVETo investigate the constituent expression of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) in human umbilical vein endothelial cells (HUVECs) and the effect of PHLPP1 gene transfer on the proliferation of the cells in vitro.

METHODSCultured HUVECs were transfected with pcDNA3-GFP or pcDNA3HA-PHLPP1 via lipofectamine 2000. The cell proliferation ability was determined by cell counting and MTT colorimetric assay, and Western blotting was used to detect the protein expression of PHLPP1 in the cells.

RESULTSNo PHLPP1 protein was detected in the non-transfected cells or pcDNA3-GFP-transfected cells. pcDNA3HA-PHLPP1 gene transfection significantly increased PHLPP1 expression in the HUVECs (P<0.01), but the cell proliferation status remained unchanged (P>0.05). The absorbance of the cells measured by MTT assay was 0.134-/+0.0152, 0133-/+0.014 and 0.137-/+0.016, with cell counts of (8.293-/+0.962)x10(5), (7.937-/+0.101)x10(5) and (8.127-/+0.112)x10(5), respectively, showing no significant differences between the 3 groups (P>0.05).

CONCLUSIONSPhosphatase PHLPP1 may not be the most important signal protein in the regulation of HUVEC proliferation.

Cell Proliferation ; Gene Transfer Techniques ; Human Umbilical Vein Endothelial Cells ; cytology ; metabolism ; Humans ; Nuclear Proteins ; genetics ; Phosphoprotein Phosphatases ; genetics ; Transfection

OBJECTIVETo study the optimum acupuncture treatment program and the mechanism for treatment of cerebral infarction.

METHODSSixty-three cases were randomly divided into 9 groups. The four factors, times of manipulation, the retaining time of the needle, acupuncture instrument and acupoints,and their corresponding three levels were adopted respectively in treatment of each group. Then nerve function defect score and insulin resistance were observed before and after treatment.

RESULTSThe acupoints, the times of manipulation and the retaining time of the needle have significant effects on nerve function defect and insulin resistance (P < 0.01 or P < 0.05), and the acupuncture instrument has a significant effect on insulin resistance (P < 0.01). The choice of acupoints was the most important factor for acupuncture treatment of cerebral infarction.

CONCLUSIONAcupuncture for regulating The Governor Vessel with twice manipulations and retaining the needle for 60 min is optimum treatment program for cerebral infarction. The good regulating effect of acupuncture on insulin resistance is one of the mechanisms of achieving the therapeutic results.

Acupuncture Points ; Acupuncture Therapy ; Cerebral Infarction ; Humans ; Insulin Resistance ; Needles

Objective To evaluate the usefulness of narrow-band imaging with magnification in differentiating colorectal lesions, and assess for a learning curve, to gave help for the clinician, who want to carry out the technique. Method We retrospectively analyzed the clinical data of 289 patients who underwent NBI combined with magnification by four endoscopic physician, from June, 2015 to June, 2016, all the lesions were biopsied, endoscopic treatment or postoperative pathology and pathological examination, and the Sano classification control. All lesions were divided into three groups according to the NBI combined with magnifying endoscopy, these three sets included both lesions requiring endoscopic treatment (e.g. target lesions) and lesions that were not, or could not be, treated by endoscopy (e.g. nontarget lesions). Each physician examined the target or non-target lesion reached 15 cases as a group. By assessing the diagnostic accuracy of the four physicians for each group of lesions, an associated learning curve of NBI combined with magnifying endoscopy was developed. Result In 289 patients, 372 lesions were found by colonoscopy. NBI combined with magnifying endoscopy was 95.1%, 98.0% and 92.0%, respectively, in the identification of tumor and non-neoplastic lesions. The accuracy of the diagnosis of target and non-target lesions was significantly higher in group 2 than in group 1 [81.7% vs 95.1% (P = 0.010) and 71.7% vs 93.4% (P = 0.000)]. There was no significant difference in the diagnostic accuracy between group 2 and group 3 (P = 0.984 and P = 0.117). Conclusion It is very useful to use narrow-band imaging and Sano CP analysis in the differential diagnosis of colorectal lesions. The endoscopists who had never used NBI or no knowledge of NBI can have effective and stable diagnostic accuracy after using NBI with magnification to diagnose 15 target and non-target lesions respectively.