Total saponins of Bolbostemma paniculatum (maxim.) Franquet exert antitumor activity against MDA-MB-231 human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway.

BACKGROUND: The aim of the present study was to examine the effects of the Bolbostemma paniculatum (Maxim.) Franquet (BP) active compound, BP total saponins (BPTS), on MDA-MB-231 cells, and investigate the underlying mechanism regarding BPTS-mediated attenuation of the PI3K/Akt/mTOR pathway. METHODS: The effect of BPTS on cytotoxicity, induction of apoptosis and migration on MDA-MB-231 cells at three different concentrations was investigated. A CCK-8 assay, wound-healing assay and flow cytometry were used to demonstrate the effects of BPTS. Additionally, expression of the primary members of the PI3K/Akt/mTOR signaling pathway was assessed using western blotting. To verify the underlying mechanisms, a PI3K inhibitor and an mTOR inhibitor were used. RESULTS: BPTS inhibited proliferation of MDA-MB-231 cells with an IC50 value of 10 µg/mL at 48 h. BPTS inhibited migration of MDA-MB-231 cells, and the western blot results demonstrated that BPTS reduced p-PI3K, p-Akt and p-mTOR protein expression levels in MDA-MB-231 cells. Additionally, the results were confirmed using a PI3K inhibitor and an mTOR inhibitor. BPTS decreased proliferation and migration of MDA-MB-231 cells possibly through inhibiting the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: The results highlight the therapeutic potential of BPTS for treating patients with triple-negative breast cancer.

[Nephro-protective effects of total triterpenoids from Psidium guajava leaves on type 2 diabetic rats].

OBJECTIVE: To investigate the nephro-protective effects of total triterpenoids from Psidium guajava leaves (TTPGL) on type 2 diabetic rats. METHODS: Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) and a high-fat diet. Diabetic rats were divided into five groups: diabetic model control, low-dose TTPGL-treated (60 mg/kg, L-TTPGL), medium-dose TTPGL-treated (120 mg/kg, M-TTPGL), high-dose TTPGL-treated (240 mg/kg, H-TTPGL) and rosiglitazone-treated (3 mg/kg, RSG). The rats received daily treatment for six weeks. At the end of the period,the levels of fasting blood glucose (FPG), fasting insulin (FINS), creatinine (Cr) and blood urea nitrogen (BUN) in serum were measured. Kidneys for histopathological evaluation were stained with Hematoxylin and Eosin (HE). RESULTS: Compared with normal control group, the level of FPG was increased, the insulin and insulin sensitivity index were decreased in the model group; The levels of BUN and Cr were increased with histopathological changes related to diabetic nephropathy in the kidney, which were the glomerular endothelium and mesangial cell proliferation, capillary narrowed, the base-membrane incrassation, glomerular swelling, cysts narrowed and tubules edema. Compared with the model group, the levels of FPG were decreased, serum insulin and insulin sensitivity index were increased significantly in M-TTPGL and H-TTPGL groups (P<0.01 or P<0.05); The levels of BUN and Cr were decreased significantly (P<0.01 or P<0.05) and the renal structural damages were improved significantly. CONCLUSION: TTPGL could decrease the level of blood glucose of diabetic rat effectively, increase the insulin sensitivity index and protect renal lesions in diabetic rats.

[Effects of extracts of Ginkgo biloba leaves on apelin concentration and expressions in plasma and myocardium of rats with myocardial ischemia injury].

OBJECTIVE: To investigate the changes of apelin in plasma and myocardium of model rats and the protective mechanisms of Extracts of Ginkgo biloba leaves (EGb) on myocardial ischemia injury induced by isoproterenol. METHODS: The model of myocardial ischemia injury was induced by subcutaneous injection of high dose isoproterenol. ELISA (enzyme linked immunosorbent assay) was used to measure the apelin concentration in plasma and myocardium. Semi-Quantitative RT-PCR was used to measure the apelin mRNA level in myocardium. The pathomorphology changes of myocardium was observed with light microscope. EGb was administered for 7 weeks. RESULTS: Compared with the normal control group, the apelin concentration in plasma and myocardium and the apelin mRNA level in myocardium significantly decreased in the model group (P < 0.01). Compared with the model group, the apelin concentration in plasma and myocardium and the apelin mRNA level in myocardium obviously increased in the EGb group (P < 0.01). Meanwhile, the NO content in serum also obviously increased and the pathological damage of myocardium was obviously improved. CONCLUSION: The protective mechanisms of EGb on myocardial ischemia injury may be related to the elevation of apelin contents and apelin mRNA level.

[Effects of EGb 761 on the cell apoptosis induced by H2O2 in RIN-m beta cells].

OBJECTIVE: To investigate the effects of ginkgo biloba extract (EGb 761) on apoptosis induced by hydrogen peroxide (H2O2) in RIN-m beta-cells. METHODS: The apoptotic model was made by H2O2 exposed for six hours with a concentration of 500 micromol/L The cytotoxicity was measured by MTT. Hoechst 33258 fluorescent staining were used to detect the protective effect of EGb 761 on the apoptosis of RIN-m beta-cells induced by H2O2. Annexin V-PI double staining of Flow cytometry were used to detect apoptosis quantitively. RESULTS: Compare to control group, after exposed to 500 micromol/L H2O2 for 6 hours, the apoptosis rate incereased and cell survival rate were decreased considerably (P < 0.01). Pretreated for 10 hours with EGb 761, the flow cytometry results showed that the apoptosis rate decreased and cell survival rate were increased considerably (P < 0.01, compared to H2O2 control group). CONCLUSION: EGb 761 can decrease RIN-m beta-cells damage and apoptosis induced by H2O2.

Total saponins of Panax notoginseng protected rabbit iliac artery against balloon endothelial denudation injury.

AIM: To investigate whether total Panax notoginseng saponins (PNS) could protect endothelium of rabbit iliac artery against balloon endothelial denudation (BED) injury. METHODS: The morphology changes of the endothelium were observed with scanning electron microscope (SEM) and hematoxylin and eosin stain after BED of rabbit iliac artery at 0, 4, 6, and 8 week respectively. Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) was also determined by immunohistochemistry. PNS 10, 30, and 50 mg/kg were administered iv per day from 2 d before to 4 weeks after operation. RESULTS: The endothelium was denudated completely after BED. At the 4th week the endothelium was repaired in some degree, then recovered gradually at 6 and 8 week. The degree of intimal thickening at 4 week was significantly greater than that at 0, 6, or 8 week. The sequence of VEGF or MMP-2 staining from strong to weak was 4, 6, 0, 8 week, and normal control. However at 4 week, endothelial regeneration in PNS 30 and 50 mg/kg groups was significantly faster than that in saline group. The intimal thickness was significantly decreased and expressions of VEGF and MMP-2 were both down-regulated in PNS 30 or 50 mg/kg groups compared with saline control group. CONCLUSION: PNS promoted the endothelial regeneration and reduced ECM thickening, which was related to regulation of the expression of VEGF and MMP-2. PNS may have sustained antirestenotic effect after BED.