Inhibitory Effect Of Ginsenoside Rg3 Research Articles

Inhibitory Effect of Ginsenoside Rg3 Combined With 5-Fluorouracil on Tumor Angiogenesis and Tumor Growth of Colon Cancer in Mice: An Experimental Study

To evaluate the inhibitory effect of ginsenoside Rg3 combined with 5-fluorouracil (5-FU) on tumor angiogenesis and tumor growth in colon cancer in mice. CT26 mouse model of colon cancer was established and the mice were randomly assigned to the control group, the ginsenoside Rg3 group, the 5-FU group, and the Rg3 combined with 5-FU group. The 5-FU group was injected intraperitoneally at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 10 days. Treatment for the Rg3 group was given at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 21 days via gastric gavage. The dose and the mode of treatment for the Rg3+5-FU combination group were the same as those for the 5-FU and the Rg3 group. The control group was intraperitoneally injected with 0.2 mL/d of normal saline for 10 days. The expression of vascular endothelial growth factor (VEGF) and CD31 and the microvascular density (MVD) of the tumor tissues were examined by immunohistochemistry. The blood flow signals and tumor necrosis were examined by color Doppler flow imaging (CDFI). The quality of life, survival rate, tumor volume, tumor mass, and tumor inhibition rate of the mice were monitored. After 21 days of treatment, the tumor volume and the tumor mass of all treatment groups were significantly decreased compared with those the control group, with the combination treatment group exhibiting the most significant decrease. The tumor inhibition rates of the Rg3 group, the 5-FU group, and the combination group were 29.96%, 68.78%, and 73.42%, respectively. Rg3 treatment alone had inhibitory effect on tumor growth to a certain degree, while 5-FU treatment alone or 5-FU combined with Rg3 had a stronger inhibitory effect on tumor growth. The tumor inhibition rate of the combination group was higher than that of the 5-FU group, but the difference was not statistically significant (P>0.05). Color Doppler ultrasound showed that there were multiple localized and large tumor necrotic areas that were obvious and observable in the Rg3 group and the combination group, and that there were only small tumor necrotic areas in the 5-FU group and the control group. The tumor necrosis rate of the combination group was (55.63±3.12)%, which was significantly higher than those of the other groups (P<0.05). CDFI examination of the blood flow inside of the tumor of the mice showed that the blood flow signals in the combination group were mostly grade 0-Ⅰ, and that the blood flow signals in the control group were the most abundant, being mostly grade Ⅱ-Ⅲ. The abundance of the blood flow signals in the Rg3 and 5-FU groups were between those of the control group and the combination group. Compared with those of the control group, the expression levels of MVD and VEGF in the tumor tissues of the Rg3 group, the 5-FU group, and the combination group were significantly decreased, with the combination group showing the most significant decrease (P<0.05). HE staining results indicated that there was significant tumor necrosis in mice in the control group and that there were more blood vessels. In contrast, in the tumor of the Rg3 group and the 5-FU group, there were fewer blood vessels and necrotic gaps appeared within the tumors. In the combination group, the tumor tissues had the fewest blood vessels and rope-like necrosis was observed. The mice started dying on the 18th day after treatment started, and all the mice in the control group died on the 42nd day. By this time, there were 3, 5, and 7 mice still alive in the Rg3 group, the 5-FU group, and the combination group, respectively, presenting a survival rate of 30%, 50%, and 70%, respectively. All mice in all the groups died on day 60 after treatment started. Ginsenoside Rg3 combined with 5-FU can significantly inhibit tumor angiogenesis and tumor growth of colon cancer in mice and improve the survival and quality of life of tumor-bearing mice.

Ginsenoside Rg3 inhibits pulmonary fibrosis by preventing HIF-1\u03b1 nuclear localisation

BackgroundExcessive fibroblast proliferation during pulmonary fibrosis leads to structural abnormalities in lung tissue and causes hypoxia and cell injury. However, the mechanisms and effective treatment are still limited.MethodsIn vivo, we used bleomycin to induce pulmonary fibrosis in mice. IHC and Masson staining were used to evaluate the inhibitory effect of ginsenoside Rg3 in pulmonary fibrosis. In vitro, scanning electron microscopy, transwell and wound healing were used to evaluate the cell phenotype of LL 29 cells. In addition, biacore was used to detect the binding between ginsenoside Rg3 and HIF-1α.ResultsHere, we found that bleomycin induces the activation of the HIF-1α/TGFβ1 signalling pathway and further enhances the migration and proliferation of fibroblasts through the epithelial mesenchymal transition (EMT). In addition, molecular docking and biacore results indicated that ginsenoside Rg3 can bind HIF-1α. Therefore, Ginsenoside Rg3 can slow down the progression of pulmonary fibrosis by inhibiting the nuclear localisation of HIF-1α.ConclusionsThis finding suggests that early targeted treatment of hypoxia may have potential value in the treatment of pulmonary fibrosis.

Inhibitory effect of ginsenoside Rg3 on cancer stemness and mesenchymal transition in breast cancer via regulation of myeloid-derived suppressor cells.

Ginsenoside Rg3 (Rg3) has been studied in several cancer models and is suggested to act through various pharmacological effects. We investigated the anticancer properties of Rg3 through myeloid-derived suppressor cell (MDSC) modulation in FM3A mouse mammary carcinoma cells. The effects of Rg3 on MDSCs and consequent changes in cancer stem-like cells (CSCs) and epithelial-mesenchymal transition (EMT) were evaluated by diverse methods. MDSCs promoted cancer by enhancing breast cancer stemness and promoting EMT. Rg3 at a dose without obvious cytotoxicity downregulated MDSCs and repressed MDSC-induced cancer stemness and EMT. Mechanistic investigations suggested that these inhibitory effects of Rg3 on MDSCs and corresponding cancer progression depend upon suppression of the STAT3-dependent pathway, tumor-derived cytokines, and the NOTCH signaling pathway. In a mouse model, MDSCs accelerated tumor progression, and Rg3 delayed tumor growth, which is consistent with the results of in vitro experiments. These results indicated that Rg3 could effectively inhibit the progression of breast cancer. The anticancer effect of Rg3 might be partially due to its downregulation of MDSCs and consequent repression of cancer stemness and EMT in breast cancer. Hence, we suggest the regulation of MDSCs through Rg3 treatment as an effective therapeutic strategy for breast cancer patients.

Ginsenoside Rg3 promotes regression from hepatic fibrosis through reducing inflammation-mediated autophagy signaling pathway

Inflammation and autophagy occur during hepatic fibrosis development caused by various pathogens, and effectively curbing of autophage may delay the occurrence of hepatic fibrosis. The current study aimed to unravel the inhibitory effects of Ginsenoside Rg3 (G-Rg3) on inflammation-mediated hepatic autophagy to curb hepatic fibrosis caused by thioacetamide (TAA)-induced subacute and chronic hepatic injury. TAA is mainly metabolized in the liver to cause liver dysfunction. After intraperitoneal injection of TAA for 4 or 10 weeks (TAA-chronic mouse models), severe inflammatory infiltration and fibrosis occurred in the liver. Treatment with G-Rg3 alleviated hepatic pathological changes and reversed hepatic fibrosis in the TAA-chronic models with decreased deposition of collagen fibers, reduced expression of HSCs activation marker (α-SMA), and reduced secretion of profibrogenic factors (TGF-β1). G-Rg3 decreased expressions of autophagy-related proteins in mice of TAA-chronic models. Notably, G-Rg3 inhibited the survival of activated rat hepatic stellate cells (HSC-T6), but had no cytotoxicity on human hepatocytes (L02 cell lines). G-Rg3 dose-dependently inhibited autophagy in vitro with less expression of p62 and fewer LC3a transformation into LC3b in inflammatory inducer lipopolysaccharide (LPS)-induced rat HSC-T6 cells. Furthermore, G-Rg3 enhanced the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in vivo and in vitro. Besides, mTOR inhibitor Rapamycin and PI3K inhibitors LY294002 were employed in LPS-treated HSC-T6 cell cultures to verify that Rg3 partially reversed the increase in autophagy in hepatic fibrosis in vitro. Taken together, G-Rg3 exerted anti-fibrosis effect through the inhibition of autophagy in TAA-treated mice and LPS-stimulated HSC-T6 cells. These data collectively unravel that G-Rg3 may serve a promising anti-hepatic fibrosis drug.

Ginsenoside Rg3 inhibits grass carp reovirus replication in grass carp ovarian epithelial cells

Ginseng exhibits multiple medicinal properties, including the improvement of immune function and enhancing disease resistance. In this study, we investigated the inhibitory effects of ginsenoside Rg3 on grass carp reovirus (GCRV) infection of grass carp ovarian (CO) epithelial cells, in order to provide a baseline framework for future high-efficacy antiviral drug screening investigations. Ginsenoside Rg3 was added to GCRV-infected CO cells, and cells were cultured at 27 °C before cell proliferation was measured by MTT assays. Label-free real-time cellular analysis (RTCA) after 72 h of experimentation demonstrated that 100 μg/mL ginsenoside Rg3 treatment had the highest inhibitory effect on GCRV (among 1,10,100 μg/mL treatments). We then measured the capacity for cellular antioxidant ability. Cells treated with 1,10,100 μg/mL ginsenoside Rg3 exhibited increases in Total Antioxidant Capacity activity relative to controls, respectively. Furthermore, Antioxidant assay and reverse transcript quantitative polymerase chain reaction (RT-qPCR) showed that ginsenoside Rg3 were efficient to restrain the replication of GCRV in CO cells. Expression analysis of immune-related genes via RT-qPCR showed that treatment with ginsenoside Rg3 promoted expression of IRF-3 and IRF-7 increases, respectively. Moreover, expression of IFN-1 was induced, which then inhibition the expression of tumor necrosis factor-alpha (TNF-α). In conclusion, we demonstrated that ginsenoside Rg3 promotes CO cell proliferation, inhibits GCRV activity, promotes CO cell immune activities, and thereby enhances the resistance of CO to GCRV infection.

Inhibitory effect of ginsenoside Rg3 on vascular growth and expression of vascular endothelial growth factor and matrix metalloproteinase-9 in breast cancer rats

Objective To explore the inhibitory effect of ginsenoside Rg3 on vascular growth and expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 in breast cancer rats. Methods The rat model of breast cancer was replicated. The successful rats were divided into model group, low dose group and high dose group according to the random number table method, 20 rats in each group, and 20 healthy rats were taken as blank control group. Rats in the blank control group and model group were given 0.5% sodium carboxymethyl cellulose solution by gavage, while those in the low-dose group and the high-dose group were given 0.5% sodium carboxymethyl cellulose solution containing ginsenoside Rg3. The volume, mass, tumor inhibition rate, microvessel density (MVD), expression of VEGF and MMP-9 were measured, and the serum levels of VEGF and MMP-9 were measured.Statisticalanalysis of data using the statistical product and service solutions 19.0 software. Results The tumor volume of model group, low dose group and high dose group were (4.83±0.66), (3.48±0.51), (1.58±0.23) cm3, and the mass of tumors were (5.17±0.59), (4.00±0.42), (2.09±0.26) g, respectively. The inhibition rates were 0.00%, 22.43%, 53.81%, respectively. The volume and mass of tumors in the low dose group and the high dose group were significantly smaller than those in the model group ( t=7.238, 20.795, 7.225, 21.364, P<0.05), the volume and mass of tumors in the high dose group were significantly smaller than those in the low dose group (t=15.188, 17.292, P<0.05), and the inhibition rate in the high dose group was significantly higher than that in the low dose group (X2=12.324, P<0.05). The MVDs in tumors and breast tissues of rats in blank control group, model group, low dose group and high dose group were (7.53±1.53), (23.52±4.21), (17.32±3.52) and (12.20±2.19), respectively. The serum levels of VEGF were (218.42±46.37), (435.67±83.21), (350.13±45.26), (278.58±30.56) mg/L, and the serum levels of MMP-9 were (230.52±32.56), (460.22±60.36), (330.73±51.57), (255.72±41.73) mg/L. The expression levels of VEGF protein in tissues were (0.23±0.09), (0.58±0.14), (0.46±0.12), (0.25±0.09). The expression levels of MMP-9 protein in tissues were (0.14±0.11), (0.82±0.22), (0.63±0.19), (0.46±0.20), respectively. MVD, VEGF and MMP-9 in the model group were significantly higher than those in the blank control group (t= 15.964, 9.405, 12.364P<0.05). MVD, VEGF and MMP-9 in the low-dose group and the high-dose group were significantly lower than those in the model group (t=5.053, 10.668, 2.910, 8.867, 2.923, 5.415, P<0.05). MVD, VEGF and MM-9 in the high-dose group were significantly lower than those in the low-dose group (t=5.523, 6.261, 2.755P<0.05). Serum levels of VEGF and MMP-9 in model group were significantly higher than those in blank control group (t=10.199, 14.978, P<0.05). Serum levels of VEGF and MMP-9 in low-dose group and high-dose group were significantly lower than those in model group (t=4.039, 7.925, 7.294, 12.463, P<0.05). Serum levels of VEGF and MMP-9 in high-dose group were significantly lower than those in low-dose group (t=5.859, 5.057, P<0.05). Conclusion Ginsenoside Rg3 can inhibit the growth of blood vessels and the expression of VEGF and MMP-9 in breast cancer model rats. Key words: Ginsenoside Rg3; Breast cancer; Rat; Vascular growth; Vascular endothelial growth factor; Matrix metalloproteinase-9

Inhibition of the hypoxia-induced factor-1α and vascular endothelial growth factor expression through ginsenoside Rg3 in human gastric cancer cells.

The aim of this study is to probe in the inhibitory effects of ginsenoside Rg3 on the expression of hypoxia-induced factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human gastric cancer cells. Human gastric cancer BGC823 cells were divided into the control group and experiment group, and expression levels of HIF-1α and VEGF were detected by immunocytochemistry and Western blot after cells were cultured under hypoxia for different durations. Under hypoxia, expression of HIF-1α and VEGF in human gastric cancer BGC823 cells showed an increasing trend, and that was remarkably lower in experiment group than in the control group after applying Rg3, which was obvious at 12 and 24 h (P < 0.05). Rg3 can inhibit expression of HIF-1α and VEGF in human gastric cancer cells and may influence abdominal implantation metastasis of gastric cancer through inhibiting its expression.

Ginsenoside Rg3 inhibits angiogenesis in a rat model of endometriosis through the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway.

ObjectiveThis study aimed to investigate the link between the inhibitory effect of ginsenoside Rg3 on the ectopic endometrium growth and the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway, a mechanism known to inhibit angiogenesis and induce ectopic endometrial cell apoptosis.Materials and methodsA model of endometriosis was established by allotransplantation in rats. The rats were randomly divided into 5 groups: the ginsenoside Rg3 low-dose group (group A,5mg/kgBW/d of ginsenoside Rg3), the ginsenoside Rg3 high-dose group (group B, 10mg/kgBW/d of ginsenoside Rg3), the gestrinone group (group C, 0.5mg/kgBW/d of gestrinone), the control group (groupD, 10ml/kg BW/d of 0.5%CMC-Na) and the ovariectomized group (group E, 10ml/kgBW/d of 0.5%CMC-Na). Rats were executed after 21 days of continuous administration. The ectopic endometrium volume was measured and the inhibitory rate was calculated. The levels of serum estradiol (E2) and progesterone (P) were detected by Electro-Chemiluminescence Immunoassay (ECLI). The protein expressionof VEGF, VEGFR-2, p-Akt, and p-mTOR inthe ectopic endometrium wastested by immunohistochemistry(IHC) and Western Blotting. The mRNA expression levels of VEGF, VEGFR-2, Akt, and mTOR were tested by Real-Time Polymerase Chain Reaction (PCR). The apoptosis rate of the ectopic endometrial cells was detected by Terminal Deoxynucleotidyl Transferase-mediated Digoxigenin-dUTP Nick-End Labeling Assay(TUNEL).Main resultsTissue measurements revealed a dose-dependent inhibition effect of ginsenoside Rg3 on the growth of the ectopic endometrium in treated rats compared to controls. Immunohistochemical and Western Blotting assays confirmed that the expression of VEGF, p-Akt, and p-mTOR was down-regulated in ginsenoside Rg3 -treated lesions. Real-time PCR results also showed that the mRNA expression levels of VEGF, Akt, and mTOR in the ectopic endometrium were reduced.ConclusionsThe present study demonstrates, for the first time, that ginsenoside Rg3 suppresses angiogenesis in developing endometrial lesions. The ginsenoside Rg3 inhibitory effect on the growth of the ectopic endometrium in EMs rats might occur through the blocking of the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway, thus halting angiogenesis and promoting the apoptosis of ectopic endometrial cells.

Intracellular Trafficking Modulation by Ginsenoside Rg3 Inhibits Brucella abortus Uptake and Intracellular Survival within RAW 264.7 Cells.

Ginsenoside Rg3, a saponin extracted from ginseng, has various pharmacological and biological activities; however, its effects against Brucella infection are still unclear. Herein, the inhibitory effects of ginsenoside Rg3 against intracellular parasitic Brucella infection were evaluated through bacterial infection, adherence assays, and LAMP-1 colocalization, as well as immunoblotting and FACS for detecting MAPK signaling proteins and F-actin polymerization, respectively. The internalization, intracellular growth, and adherence of Brucella abortus in Rg3-treated RAW 264.7 cells were significantly decreased compared with the Rg3-untreated control. Furthermore, an apparent reduction of F-actin content and intensity of F-actin fluorescence in Rg3-treated cells was observed compared with B. abortus-infected cells without treatment by flow cytometry analysis and confocal microscopy, respectively. In addition, treating cells with Rg3 decreased the phosphorylation of MAPK signaling proteins such as ERK 1/2 and p38 compared with untreated cells. Moreover, the colocalization of B. abortus-containing phagosomes with LAMP-1 was markedly increased in Rg3-treated cells. These findings suggest that ginsenoside Rg3 inhibits B. abortus infection in mammalian cells and can be used as an alternative approach in the treatment of brucellosis.

Ginsenoside Rg3 inhibits colon cancer cell migration by suppressing nuclear factor kappa B activity

ObjectiveTo study the mechanism of the inhibitory effect of ginsenoside Rg3 on colon cancer cell migration. MethodsTranswell migration assays were performed to investigate the inhibitory effect of ginsenoside Rg3 on SW480 cell migration. Electrophoretic mobility shift assays (EMSAs) and dual luciferase reporter assays were used to study the suppression capability of Rg3 on nuclear factor kappa B (NF-κB) activity. Western blotting was adopted to determine protein levels. ResultsTwo-hundred micromolar ginsenoside Rg3 significantly inhibited SW480 cell migration (P < 0.05). EMSA showed that Rg3 suppressed the DNA binding ability of NF-κB. Dual luciferase reporter assay showed that Rg3 decreased NF-κB-regulated gene transcription (P < 0.01). Western blots indicated that Rg3 down-regulated expression of the NF-κB-regulated matrix metalloproteinase 9, cyclooxygenase-2 and C-Myc. An NF-κB inhibitor, pyrrolidine dithiocarbamate, enhanced the inhibitory effect of Rg3 on SW480 cell migration. ConclusionGinsenoside Rg3 has a strong antitumor migration capability by suppressing NF-κB activity and expression of NF-κB-regulated gene products. It could be a good adjuvant for colon cancer patients during the course of chemotherapy.

Ginsenoside Rg3 enhances the inhibitory effects of chemotherapy on esophageal squamous cell carcinoma in mice.

The present study was conducted in order to investigate the inhibitory effects of ginsenoside Rg3 combined with chemotherapy on Eca-109 esophageal squamous cell carcinoma (ESCC) in mice. Tumor xenograft models were established in the right forelimb of 20 BALB/c nude mice by subcutaneous injection. The tumor-bearing mice were randomly assigned to 4 treatment groups (n=5 per group) as follows: the control group (saline), the ginsenoside Rg3 alone group (6 mg/kg/day, once a day for 3 weeks), the chemotherapy alone group (paclitaxel 10 mg/kg/day + cisplatin 5 mg/kg/day on days 1, 7, 14 and 21) and the chemotherapy + Rg3 group (combined treatment). The length and width of the tumor were directly measured with calipers at different time points and the tumor volume (cm3) was calculated using the formula 0.52 × length × width2 every other day. The mice were sacrificed by cervical dislocation following completion of therapy, the tumors were removed and weighed and the expression levels of Ki-67 were determined by immunohistochemistry. The results indicated that the coadministration of ginsenoside Rg3 significantly enhanced the inhibitory effects of chemotherapy on tumor growth. In addition, the expression levels of Ki-67 in the chemotherapy + Rg3 group were significantly lower compared to those in the other 3 groups. The chemotherapy + Rg3 group also exhibited the lowest microvascular density among all four groups. These findings suggested that ginsenoside Rg3 may improve the antitumor efficacy of chemotherapy in Eca-109 ESCC in mice.

Inhibitory Effect of Ginsenoside Rg3 on Growth，Metastasis and Expression of TAMs in Mice Lung Adenocarcinoma

Inhibitory Effect of Ginsenoside Rg3 on Growth，Metastasis and Expression of TAMs in Mice Lung Adenocarcinoma

Inhibitory effect of ginsenoside Rg3 on the tube-like structure formation in human nasopharyngeal carcinoma HNE-1 cell line in vitro

To study the anti-angiogenic effect of ginsenoside Rg3 (Rg3 in abbreviation) in human nasopharyngeal carcinoma HNE-1 cells in vitro. The tube-like structure (TLS) formation of HNE-1 cells, cultured in medium with different concentrations of Rg3, was determined by in vitro anti-angiogenic test based on preliminary experiment observing the TLSs formed by HNE-1 cells on Matrigel and their structural characteristics. The VEGF expression level in HNE-1 cells was determined by immunohistochemistry (IHC) and Western-blot test after 48-hour cultured in medium with different concentrations of Rg3. HNE-1 cells could form TLSs and mosaic vessels when mix-cultured with CRL-2480 on Matrigel. Rg3 could inhibit the TLS formation of HNE-1 cells. After 24-hour culture in medium with Rg3 at concentrations of 0, 50, 100 and 200 µg/ml, the number of TLSs were 75.50 ± 6.86, 55.00 ± 11.92, 39.75 ± 7.93 and 24.50 ± 6.25, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.928; P < 0.01). After 48 hours of culture, the expressions of VEGF significantly declined by IHC test with results as 0.19 ± 0.03, 0.13 ± 0.02, 0.11 ± 0.01, and 0.08 ± 0.01, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.911; P < 0.01). The expressions of VEGF also gradually decreased as revealed by Western blot test, with corresponding results as 119.49, 111.51, 86.45, and 38.29. All of the tests showed significantly declined results in the group at the concentration of 200 µg/ml Rg3. Rg3 can inhibit the vasculogenic mimicry of HNE-1 cells, and the possible mechanism might be associated with the down-regulation of VEGF protein expression in HNE-1 cells.

Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice

BackgroundGinsenoside Rg3, a saponin extracted from ginseng, inhibits angiogenesis. The combination of low-dose chemotherapy and anti-angiogenic inhibitors suppresses growth of experimental tumors more effectively than conventional therapy or anti-angiogenic agent alone. The present study was designed to evaluate the efficacy of low-dose gemcitabine combined with ginsenoside Rg3 on angiogenesis and growth of established Lewis lung carcinoma in mice.MethodsC57L/6 mice implanted with Lewis lung carcinoma were randomized into the control, ginsenoside Rg3, gemcitabine and combination group. The quality of life and survival of mice were recorded. Tumor volume, inhibitive rate and necrosis rate were estimated. Necrosis of tumor and signals of blood flow as well as dynamic parameters of arterial blood flow in tumors such as peak systolic velocity (PSV) and resistive index (RI) were detected by color Doppler ultrasound. In addition, expression of vascular endothelial cell growth factor (VEGF) and CD31 were observed by immunohistochemstry, and microvessel density (MVD) of the tumor tissues was assessed by CD31 immunohistochemical analysis.ResultsQuality of life of mice in the ginsenoside Rg3 and combination group were better than in the control and gemcitabine group. Combined therapy with ginsenoside Rg3 and gemcitabine not only enhanced efficacy on suppression of tumor growth and prolongation of the survival, but also increased necrosis rate of tumor significantly. In addition, the combination treatment could obviously decrease VEGF expression and MVD as well as signals of blood flow and PSV in tumors.ConclusionGinsenoside Rg3 combined with gemcitabine may significantly inhibit angiogenesis and growth of lung cancer and improve survival and quality of life of tumor-bearing mice. The combination of chemotherapy and anti-angiogenic drugs may be an innovative and promising therapeutic strategy in the experimental treatment of human lung cancer.

Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR‐γ signal pathways

Ginsenosides, the active component of ginseng, exerts antidiabetic and anticancer effects. This study investigated the molecular basis of ginsenoside Rg3, a red ginseng rich constituent, focusing on its ability to inhibit adipocyte differentiation in 3T3-L1 cells. The data show that ginsenoside Rg3 was effective in the inhibition of adipocyte differentiation. This inhibitory effect of ginsenoside Rg3 on adipocyte differentiation was accompanied by PPAR-gamma inhibition in rosiglitazone-treated cells. The study also tested whether AMP-activated protein kinase (AMPK) activation was involved in the inhibitory effects of ginsenoside Rg3. AMPK plays a role in maintaining health in the context of diseases such as type 2 diabetes, obesity and cancer. AMPK was reported to control nutritional and hormonal signal modulating. Rg3 significantly and time-dependently activated AMPK. Taken together, these results suggest that the antiobesity effect of red ginseng rich constituent, ginsenoside Rg3, involves the AMPK signaling pathway and PPAR-gamma inhibition.

Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer

Ginsenoside Rg3, the main component isolated from ginseng, inhibits some kinds of tumour growth and angiogenesis. The combination of low dose chemotherapy and antiangiogenesis inhibitors suppresses growth of experimental tumours more effectively than conventional therapy. The effect of this combination on ovarian cancer remains to be evaluated. Therefore, we investigated the synergism of ginsenoside Rg3 and cyclophosphamide (CTX) on growth and angiogenesis of human ovarian cancer. Twenty-eight female athymic mice were divided randomly into 4 groups of 7: ginsenoside Rg3, CTX, ginsenoside Rg3 and CTX combination and control, after being transplanted with ovarian cancer cells (SKOV-3). The mice were given intraperitoneal injection of ginsenoside Rg3 and CTX for the 10 days following inoculation of SKOV-3 cells. The life quality and number of living days of mice were recorded. The size of tumour, tumour inhibitive rate, life elongation rate, proliferating cell nuclear antigen labelling index (PCNALI), expression of vascular endothelial cell growth factor (VEGF) and microvessel density (MVD) of the tumour tissues were estimated. Life quality of mice in ginsenoside Rg3 and combined treatment groups were better and number of living days longer than control. Average tumour weights of each treated group were less than control and there was no significant difference among the treated groups. PCNALI of treated groups was lower than control. The MVD value and VEGF expression in treated groups were significantly lower than control and the MVD values of ginsenoside Rg3 and combined treatment groups were lower than that of CTX group. Ginsenoside Rg3 significantly inhibited growth and angiogenesis of ovarian cancer when used alone or combined with CTX. Ginsenoside Rg3 and CTX combination reinforced the antitumour effect each other and improved the living quality and survival time of mice with tumour.

Characterization of ginseng saponin ginsenoside-Rg3 inhibition of catecholamine secretion in bovine adrenal chromaffin cells

Since ginsenoside-Rg3, one of the panaxadiol saponins isolated from the ginseng root, significantly inhibited the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh), the properties of ginsenoside-Rg3 inhibition were investigated. Although ginsenoside-Rg3 inhibited the secretion evoked by ACh in a concentration-dependent manner, it affected the secretion stimulated by high K+ or veratridine, an activator of the voltage-sensitive Ca2+ or Na+ channels, only slightly. The ACh-induced Na+ and Ca2+ influxes into the cells were also reduced by ginsenoside-Rg3. The inhibitory effect of this saponin on the secretion of catecholamines was not altered by increasing the external concentration of ACh or Ca2+. The ACh-evoked secretion of catecholamines was completely restored in cells that were preincubated with 10 μM ginsenoside-Rg3 and then incubated without the saponin, whereas secretion was not completely restored in cells that were preincubated with 30 μM of this compound. Above 30 μM ginsenoside-Rg3 increased the fluorescence anisotropy of diphenylhexatriene in the cells. Furthermore, the inhibitory effect of ginsenoside-Rg3 at 30 μM on the ACh-evoked secretion of catecholamines was dependent upon the preincubation time, but this was not the case at 10 μM. These results strongly suggest that ginsenoside-Rg3 blocks the nicotinic ACh receptor-operated cation channels, inhibits Na+ influx through the channels, and consequently reduces both Ca2+ influx and catecholamine secretion in bovine adrenal chromaffin cells. In addition to this action, the ginsenoside at higher concentrations modulates the fluidity of the plasma membrane, which probably contributes to the observed reduction in the secretion of catecholamines.

Inhibitory Effect of Tumor Induced Angiogenesis by Ginsenoside Rg3

Objective The aim of the present study was to examine the mechanism of Inhibitory effect of ginsenoside Rg3 on tumor growth.Methods We investigated the inhibitory effect of Rg3 on tumor neovascular by the method of immunohistochemistry,chick chorioallantoic membrane(CAM) and Lewis lung carcinoma model.,Results We demonstrate that Rg3 can obviously inhibits angiogenesis of the CAM with a Bl=62,4~45,6.Treatment with Rg3 in vivo can obviously inhibits Lewis lung carcinoma growth with the inhibition ratio from 30% to about 50%.We also observed that the number of neovascular of the tumor in group Rg3 obviously reduced.Immunohistochemistry showed that bFGF expressing in tumor cells decreased obviously.Conclusion Rg3 can obviously inhibit the growth of Lewis lung cancer and angiogenesis of malignant tumor.