rg3整理版

胰岛 胰岛 1. J Clin Biochem Nutr. 2010 Jan;46(1):30-5. Epub 2009 Dec 29. Ginsenoside Rg3 Suppresses Palmitate-Induced Apoptosis in MIN6N8 Pancreatic beta-Cells. Kim K, Park M, Young Kim H. Functional Food Technology Research Group, Research Division for Emerging Innovative Techology, Korea Food Research Institute, 516 Baekhyun-dong, Bundang-gu, Songnam-si, Kyonggi-do 463-746, Republic of Korea. Chronic exposure to elevated levels of free fatty acids (FFA) causes beta-cell dy function and may induce beta-cell apoptosis in type 2 diabetes. The execution of beta-cell apoptosis occurs through activation of mitogen-activated protein kinases (MAPKs). Ginsenoside Rg3 (Rg3), one of the active ingredients of ginseng saponins, has not been known about the effects on beta-cell apoptosis mediated with FFA. The aims of this study were to investigate the in vitro protective effects of Rg3 on MIN6N8 mouse insulinoma beta-cells against FFA-induced apoptosis, as well as the modulating effects on p44/42 MAPK activation. Our results showed that Rg3 inhibited the palmitate-induced apoptosis through modulating p44/42 MAPK activation. We conclude that Rg3 has the potential role in suppressing the progression of type 2 diabetes by inhibiting FFA-mediated loss of beta-cells. PMCID: PMC2803130 PMID: 20104262 [PubMed - in process] 5. Biochem Biophys Res Commun. 2009 Nov 6;389(1):70-3. Epub 2009 Aug 21. The ginsenoside Rg3 has a stimulatory effect on insulin signaling in L6 myotubes. Kim M, Ahn BY, Lee JS, Chung SS, Lim S, Park SG, Jung HS, Lee HK, Park KS. Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Republic of Korea. The ginsenoside Rg3 is known to have a protective effect against hyperglycemia, obesity and diabetes in vivo. In this study, we examined the effect of Rg3 on insulin signaling and glucose uptake in cultured L6 myotubes. Rg3 increased glucose uptake both in the basal and insulin-induced states of L6 myotubes. Consistent with the increase in glucose uptake, Rg3 stimulated the phosphorylation of IRS-1 and Akt. Interestingly, Rg3 dramatically increased IRS-1 protein levels, while the protein level of Akt was not affected. Rg3 regulated IRS-1 expression at the transcriptional level and also increased the level of GLUT4 mRNA. Treatment of ginsam, in which Rg3 is the major compound of ginsenosides, increased the IRS-1 protein levels in OLEFT rats. In addition, we found that this effect of Rg3 on insulin signaling was not mediated by the AMPK pathway. In conclusion, these results suggest that Rg3 improves insulin signaling and glucose uptake primarily by stimulating the expression of IRS-1 and GLUT4. PMID: 19699714 [PubMed - indexed for MEDLINE] 6. Ai Zheng. 2009 May;28(5):461-5. [Effect of ginsenoside Rg3 on Pim-3 and Bad proteins in human pancreatic cancer cell line PANC-1] [Article in Chinese] Jian J, Hu ZF, Huang Y. Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Molecular Medicine, Nanchang, Jiangxi, China. BACKGROUND AND OBJECTIVE: Ginsenoside Rg3 is a traditional Chinese medicine monomer which possesses anticancer effects. This study was to investigate the effects of ginsenoside Rg3 on Pim-3 and phosphorylated Bad (pBad) proteins, pBad (Ser112) and pBad (Ser136) in human pancreatic cancer cell line PANC-1. METHODS: PANC-1 cells were exposed to 10, 20, 40 and 80 micromol/L ginsenoside Rg3 for 24 h. A short hairpin RNA (shRNA) of Pim-3 was cloned and inserted into a eukaryotic expression vector pSilencer 3.1-H1 Neo to construct pSilencer 3.1-H1 Neo-Pim-3. pSilencer 3.1-H1 Neo-Pim-3 was then transfected into PANC-1 cells. Cell proliferation was measured by MTT assay; cell apoptosis was observed under an invert microscope and measured by flow cytometry with Annexin V/PI staining; protein expressions of Pim-3, Bad, pBad (Ser112) and pBad (Ser136) were measured by Western blot. RESULTS: The inhibitory rates of 10, 20, 40 and 80 micromol/L ginsenoside Rg3 on PANC-1 cells were 20.2%, 33.4%, 52.8% and 65.3%, respectively. Typical morphological changes in apoptosis were induced by ginsenoside Rg3. The apoptotic rate of PANC-1 cells was significantly higher in the ginsenoside Rg3 treatment group (80 micromol/L) than in the control group (12.2% vs. 3.3%, P<0.05). Ginsenoside Rg3 had no influence on the total Bad protein expression, but decreased both Pim-3 and pBad (Ser112) expressions in a dose-dependent manner. pBad (Ser136) was not expressed in PANC-1 cells. Compared with the control group, the percentages of early and total apoptotic cells were significantly increased in PANC-1 cells transfected with pim-3-shRNA [(11.5+/-3.7)% vs. (5.8+/-2.2)%,P<0.01;(20.8+/-2.6)% vs.(13.0+/-4.1)%,P<0.05], while the expressions of pim-3 and pBad (Ser112) were both decreased. CONCLUSION: The anti-tumor effect of ginsenoside Rg3 may be associated with the decrease of Pim-3 and pBad (Ser112). PMID: 19624871 [PubMed - in process] 20. Metabolism. 2009 Jan;58(1):8-15. Effect of ginsam, a vinegar extract from Panax ginseng, on body weight and glucose homeostasis in an obese insulin-resistant rat model. Lim S, Yoon JW, Choi SH, Cho BJ, Kim JT, Chang HS, Park HS, Park KS, Lee HK, Kim YB, Jang HC. Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, South Korea. Extracts of ginseng species show antihyperglycemic activity. We evaluated the antihyperglycemic and antiobesity effects of ginsam, a component of Panax ginseng produced by vinegar extraction, which is enriched in the ginsenoside Rg3. Otsuka Long-Evans Tokushima Fatty rats, an obese insulin-resistant rat model, were assigned into 1 of 3 groups (n = 8 each): controls (isotonic sodium chloride solution, 5 mL/d), rats given 300 mg/(kg d) ginsam, and rats given 500 mg/(kg d) ginsam. An intraperitoneal 2-hour glucose tolerance test was performed at the end of the 6-week treatment. After 8 weeks, body and liver weights, visceral fat measured by computed tomography, and fasting glucose and insulin concentrations and lipid profiles were recorded. Insulin-resistant rats treated with ginsam had lower fasting and postprandial glucose concentrations compared with vehicle-treated rats. Importantly, overall glucose excursion during the intraperitoneal 2-hour glucose tolerance test decreased by 21.5% (P < .01) in the treated rats, indicating improved glucose tolerance. Plasma insulin concentration was significantly lower in ginsam-treated rats. These changes may be related to increased glucose transporter 4 expression in skeletal muscle. Interestingly, when the data from both ginsam-treated groups were combined, body weight was 60% lower in the ginsam-treated rats than in the controls (P < .01). Liver weight and serum alanine aminotransferase concentrations were also lower in the ginsam-treated rats. These effects were associated with increased peroxisome proliferator-activated receptor gamma expression and adenosine monophosphate-activated protein kinase phosphorylation in liver and muscle. Our data suggest that ginsam has distinct beneficial effects on glucose metabolism and body weight control in an obese animal model of insulin resistance by changing the expression of genes involved in glucose and fatty acid metabolism. PMID: 19059525 [PubMed - indexed for MEDLINE] 39. Biol Pharm Bull. 2008 Apr;31(4):748-51. 20(S)-ginsenoside Rg3 enhances glucose-stimulated insulin secretion and activates AMPK. Park MW, Ha J, Chung SH. Department of Life and Nanopharmaceutical and Department of Pharmaceutical Science, Kyung Hee University, Seoul130-701, Korea. Although Panax ginseng has been widely used in oriental countries for pharmacological effects such as anti-diabetic, anti-inflammatory, adaptogenic and anti-fatigue activities, the active ingredient is not yet fully identified. In our preliminary studies, protopanaxadiol ginsenosides showed the insulin secretion-stimulating activity. In HIT-T15 cells, Rg3 enhanced the insulin secretion in a concentration dependent manner. This effect, however, was almost completely abolished in the presence of diazoxide (K+ channel opener) or nifedipine (Ca2+ channel blocker). Oral glucose tolerance test (OGTT) was also performed using ICR mice and Rg3 suppressed the blood glucose levels from rising by enhancing an insulin secretion at 30 min after administration. From these studies, we may conclude that Rg3 lowered the plasma glucose level by stimulating an insulin secretion and this action was presumably associated with ATP sensitive K+ channel. Next, to explore the hypothesis that ginsenoside Rg3 epimers may exhibit differential effects, glucose-stimulated insulin secretion activity and phosphorylation of AMP-activated protein kinase (AMPK) were compared between 20(S)- and 20(R)-ginsenoside Rg3. 5 microM of 20(S)-Rg3 enhanced the glucose-stimulated insulin secretion by 58% compared to the control, but 20(R)-Rg3 did not show any effect. In C2C12 myotubes, 20(S)- and 20(R)-Rg3 both markedly phosphorylated AMPK and acetyl-CoA carboxylase (ACC), although 20(R)-Rg3 showed a little less effect. Taken together, our results suggest that ginsenoside Rg3 epimers showed differential activities, and 20(S)-Rg3 epimer exhibited the higher pharmacological effects in insulin secretion and AMPK activation than 20(R)-Rg3. The novel characteristics of 20(S)-Rg3 may be a valuable candidate for anti-diabetic agent. PMID: 18379076 [PubMed - indexed for MEDLINE] 46. J Microbiol Biotechnol. 2007 Jul;17(7):1127-33. Bifidus fermentation increases hypolipidemic and hypoglycemic effects of red ginseng. Trinh HT, Han SJ, Kim SW, Lee YC, Kim DH. Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea. Antihyperlipidemic and antihyperglycemic effects of Red Ginseng (RG, steamed and dried root of Panax ginseng C. A. Meyer, family Araliaceae), major component of which is ginsenoside Rg3, and Bifidodoterium-fermented RG (FRG), major component of which is ginsenoside Rh2, were investigated. Orally administered RG and FRG potently reduced the serum triglyceride levels in corn-oil-induced hypertriglycemidemic mice as well as total cholesterol and triglyceride levels in Triton WR-1339-induced hyperlipidemic mice. Of the saponin and polysaccharide fractions of RG and FRG, the polysaccharide fraction inhibited postprandial blood glucose elevation of maltose- or starch-loaded mice and reduced the blood triglyceride levels in corn-oil-induced hypertriglycemidemic mice. The saponin fraction and its ginsenosides Rg3 and Rh2 reduced blood triglyceride and total cholesterol levels in Triton WR1339-induced hyperlipidemic mice. The inhibitory effect of FRG and its main constituents against hyperlipidemia and hyperglycemia in mice were more potent than those of RG. These findings suggest that hypolipidemic and hypoglycemic effects of RG can be enforced by Bifidus fermentation and FRG may improve hyperlipidemia and hyperglycemia. PMID: 18051323 [PubMed - indexed for MEDLINE] 49. Ai Zheng. 2007 Nov;26(11):1215-20. [Correlation of insulin-like growth factor-1 (IGF-1) to angiogenesis of breast cancer in IGF-1-deficient mice] [Article in Chinese] Tang HB, Ren YP, Zhang J, Ma SH, Gao F, Wu YP. Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China. BACKGROUND & OBJECTIVE: Insulin-like growth factors (IGFs) play important roles in the development and progression of tumors. But the mechanism of tumorigenesis in relation to IGF-1 is unclear yet. This study was to explore the correlation of circulating IGF-1 level to the angiogenesis of breast cancer in IGF-1-deficient mice. METHODS: The liver-specific IGF-1-deficient (LID) mice and control mice were injected with 7,12-dimethybenz(a)anthracene (DMBA) to develop breast cancer. Ginsenoside Rg3 was used to intervene tumor growth. The occurrence rates of breast cancer were compared. The expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) was detected by immunohistochemistry. RESULTS: The occurrence rate of breast cancer was 66.67% in untreated control mice, 33.33% in untreated LID mice, 36.00% in Rg3-treated control mice, and 12.00% in Rg3-treated LID mice. The tumor size was (0.79+/-0.20) cm in untreated control mice, (0.37+/-0.08) cm in untreated LID mice, (0.32+/-0.08) cm in Rg3-treated control mice, and (0.15+/-0.05) cm in Rg3-treated LID mice. The average light density and positive rate of VEGF were the highest in untreated control mice (0.34+/-0.10 and 0.04+/-0.02, P<0.05), and the lowest in Rg3-treated LID mice (0.13+/-0.03 and 0.01+/-0.00, P<0.05). The MVD was 31.9+/-5.3 in untreated control mice, 26.8+/-4.9 in untreated LID mice, 20.1+/-4.9 in Rg3-treated control mice, and 14.4+/-4.9 in Rg3-treated LID mice. CONCLUSIONS: Circulating IGF-1 plays a role in the onset and development of breast cancer. Degrading serum IGF-1 level could inhibit angiogenesis and growth of breast cancer. Rg3 could promote this effect. PMID: 17991321 [PubMed - indexed for MEDLINE] 联合 2. Eur J Pharmacol. 2010 Apr 10;631(1-3):1-9. Epub 2010 Jan 6. Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-kappaB. Kim SM, Lee SY, Cho JS, Son SM, Choi SS, Yun YP, Yoo HS, Yoon do Y, Oh KW, Han SB, Hong JT. College of Pharmacy, Chungbuk National University, 48, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea. Ginsenoside Rg3 has been a subject of interest for use as a cancer preventive or therapeutic agent. Nuclear factor-kappa (NF-kappaB) is constitutively activated in prostate cancer, and gives cancer cells resistance to chemotherapeutic agents. To investigate whether Rg3 can suppress the activation of NF-kappaB, and thus increase susceptibility of prostate (LNCaP and PC-3, DU145) cells against chemotherapeutics, prostate cancer cell growth as well as activation of NF-kappaB was examined. We found that a combination treatment of Rg3 (50 microM) with a conventional agent docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis as well as G(0)/G(1) arrest accompanied with the significant inhibition of NF-kappaB activity than those by treatment of Rg3 or docetaxel alone. It was also found that NF-kappaB target gene expression of Bax, caspase-3, and caspase-9 was much more significantly enhanced, but the expression of Bcl-2, inhibitor of apoptosis protein (IAP-1) and X chromosome IAP (XIAP), and the expression of cell cycle regulatory proteins cyclin B, D1 and E, and cyclin dependent kinases 2 and 4 was also much more significantly inhibited by the combination treatment. The combination of Rg3 (50 microM) with cisplatin (10 microM) and doxorubicin (2 microM) was also more effective in the inhibition of prostate cancer cell growth and NF-kappaB activity than those by the treatment of Rg3 or chemotherapeutics alone. These results indicate that ginsenoside Rg3 inhibits NF-kappaB, and enhances the susceptibility of prostate cancer cells to docetaxel and other chemotherapeutics. Thus, ginsenoside Rg3 could be useful as an anti-cancer agent. Copyright (c) 2009 Elsevier B.V. All rights reserved. PMID: 20056115 [PubMed - in process] 7. BMC Cancer. 2009 Jul 23;9:250. Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice. Liu TG, Huang Y, Cui DD, Huang XB, Mao SH, Ji LL, Song HB, Yi C. Division of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China. liutaiguo031@126.com BACKGROUND: Ginsenoside 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. METHODS: C57L/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. RESULTS: Quality 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. CONCLUSION: Ginsenoside 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. PMCID: PMC2721848 PMID: 19624862 [PubMed - indexed for MEDLINE] 9. Arch Pharm Res. 2009 May;32(5):755-65. Epub 2009 May 27. Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel. Kim SM, Lee SY, Yuk DY, Moon DC, Choi SS, Kim Y, Han SB, Oh KW, Hong JT. College of Pharmacy, Chungbuk National University, Cheongju, 361-763, Korea. Ginsenoside Rg3, the main constituent isolated from Panax ginseng, has been of interest for use as a cancer preventive or therapeutic agent. We investigated here whether Rg3 can inhibit the activity of NF-kappaB, a key transcriptional factor constitutively activated in colon cancer that confers cancer cell resistance to chemotherapeutic agents. To investigate whether RG3 can suppress activation of NF-kappaB, and thus inhibit cancer cell growth, we examined the susceptibility of colon cancer cells (SW620 and HCT116) to treatment with Rg3 (25, 50, 75, 100 microM) and RG3-induced activation of NF-kappaB. RG3 dose-dependently inhibited cancer cell growth through induction of apoptosis and decreased NF-kappaB activity. In a further study of compounds in colon cancer, we used half of the IC(50) dose, values in combined treatments of Rg3 (50 microM) with conventional agents - docetaxel (5 nM), paclitaxel (10 nM) cisplatin (10 microM) and doxorubicin (2 microM). Compared to treatment with Rg3 or chemotherapy alone, combined treatment was more effective (i.e., there were synergistic effects) in the inhibition of cancer cell growth and induction of apoptosis and these effects were accompanied by significant inhibition of NF-kappaB activity. NF-kappaB target gene expression of apoptotic cell death proteins (Bax, caspase-3, caspase-9) was significantly enhanced, but the expression of anti-apoptotic genes and cell proliferation marker genes (Bcl-2, inhibitor of apoptosis protein (IAP-1) and X chromosome IAP (XIAP), Cox-2, c-Fos, c-Jun and cyclin D1) was significantly inhibited by the combined treatment compared to Rg3 or docetaxel alone. These results indicate that ginsenoside Rg3 inhibits NF-kappaB, and enhances the susceptibility of colon cancer cells to docetaxel and other chemotherapeutics. Thus, ginsenoside Rg3 could be usef