Panax notoginseng saponins suppress radiation-induced osteoporosis by regulating bone formation and resorption. Abstract Background: While radiation-based therapies are effective for treating numerous malignancies, such treatments can also induce osteoporosis.
Purpose: We assessed the antiosteoporotic properties of total saponins extracted from the leaves of Panax notoginseng (LPNS) in a mouse model of radiation-induced osteoporosis and in vitro.
Study design/methods: The bone mineral densities, the marker of bone formation and resorption, and inflammatory factors were measured in vivo. Cell proliferation and differentiation were detected in vitro.
Results: The results showed that bone mineral densities in irradiated mice administered LPNS were significantly increased compared to those in irradiated mice which had not received LPNS. LPNS attenuated the inflammation caused by irradiation, and significantly increased blood serum AKP activity, the mRNA levels of RUNX2 and osteoprotegerin, and the numbers of CFU-Fs formed by bone marrow cells collected from irradiated mice. In contrast, LPNS decreased the numbers of osteoclast precursor cells ([CD117.sup.+]/[RANKL.sup.+] cells and [CD71.sup.+]/[CD115.sup.+] cells) and the mRNA levels of TRAP and ATP6L These results suggest that LPNS functions as a negative regulator of bone resorption. In vitro assays showed that LPNS promoted the differentiation of bone marrow mesenchymal stem cells and mononuclear cells into osteoblasts and osteoclasts, respectively, but had no effect on osteoclast activation.
Conclusion: These results demonstrate that LPNS has significant antiosteoporotic activity, which may warrant further investigations concerning its therapeutic effects in treating radiation-induced osteoporosis.
Source : Phytomedicine: International Journal of Phytotherapy + Phytopharmacology Link to Full Article
Chemopreventive Effects of Heat-processed Panax quinquefolius Root on Human Breast Cancer Cells
1Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
2Department of Anesthesia and Critical Care, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
3Department of Pathology, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
4Department of Surgery, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
5Ben May Department for Cancer Research, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
6Committee on Clinical Pharmacology and Pharmacogenomics, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
Abstract Background: Former studies have shown that extract from American ginseng (Panax quinquefolius) may possess certain antiproliferative effects on cancer cells. In this study, the chemical constituents of both untreated and heat-processed American ginseng and their antiproliferative activities on human breast cancer cells were evaluated.
Materials and Methods: American ginseng roots were steamed at 120°C for 1 h or 2 h. The major ginsenosides in the two steamed and in the unsteamed extracts were quantitatively determined using high performance liquid chromatography (HPLC). The antiproliferative activities of these extracts and individual ginsenosides on MCF-7 and MDA-MB-231 breast cancer cells were assayed using the MTS method. The effects of the extracts and the ginsenosides on the induction of cell apoptosis, the expression of cyclins A and D1, and cell cycle arrest were evaluated.
Results: Compared to the untreated extract, heat-processing reduced the content of ginsenosides Rb1, Re, Rc and Rd, and increased the content of Rg2 and Rg3. After 2 h steaming, the percent content of ginsenoside Rg3 was increased from 0.06% to 5.9% . Compared to the unsteamed extract, the 2 h steamed extract significantly increased the antiproliferative activity and significantly reduced the number of viable cells. The steamed extract also significantly reduced the expression of cyclin A and cyclin D1. The cell cycle assay showed that the steamed extract and ginsenoside Rg3 arrested cancer cells in G1-phase.
Conclusion: Heat-processing of American ginseng root significantly increases antiproliferative activity and influences the cell cycle profile.
20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action W Wang1,4, H Wang2,4, E R Rayburn1, Y Zhao1,3, D L Hill1 and R Zhang1
1Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham AL 35294, USA
2Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China
3Shenyang Pharmaceutical University, Shenyang 110016, PR China
Abstract We recently isolated 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD), a natural product from Panax notoginseng, and demonstrated its cytotoxicity against a variety of cancer cells. Here we report the effects of this compound in vitro and in vivo on human prostate cancer cells, LNCaP (androgen-dependent) and PC3 (androgen-independent), in comparison with three structurally related ginsenosides, ginsenoside Rh2, ginsenoside Rg3, and 20(S)-protopanaxadiol. Of the four test compounds, 25-OCH3-PPD was most potent. It decreased survival, inhibited proliferation, induced apoptosis, and led to G1 cell cycle arrest in both cell lines. It also decreased the levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cdks 2 and 4) and increased or activated pro-apoptotic proteins (cleaved PARP, cleaved caspase-3, -8, and -9). In LNCaP cells, 25-OCH3-PPD inhibited the expression of the androgen receptor and prostate-specific antigen. Moreover, 25-OCH3-PPD inhibited the growth of prostate cancer xenograft tumours. Combining 25-OCH3-PPD with conventional chemotherapeutic agents or with radiation led to potent antitumour effects; tumour regression was almost complete following administration of 25-OCH3-PPD and either taxotere or gemcitabine. 25-OCH3-PPD also demonstrated low toxicity to noncancer cells and no observable toxicity in animals. In conclusion, our preclinical data indicate that 25-OCH3-PPD is a potential therapeutic agent against both androgen-dependent and androgen-independent prostate cancer.
....Although the four ginsenosides share a common core structure, they have remarkably different effects on cancer cells. Of those tested, 25-OCH3-PPD demonstrated the most potent cytotoxic, antiproliferative, pro-apoptotic, and cell cycle regulatory effects. Moreover, it produced strong antitumour effects against a model of androgen-independent prostate cancer both alone and in combination with conventional cancer therapies. These results indicate that 25-OCH3-PPD may be an appropriate candidate for further preclinical and clinical development as an antiprostate cancer agent either alone or in combination with conventional therapies.
Effects of Triterpenoid Glycosides from Fresh Ginseng Berry on SW480 Human Colorectal Cancer Cell Line Jing-Tian Xie, MD,1,2 Guang-Jian Du, PhD,1,2 Eryn McEntee, MS,1,2 Han H. Aung, MD,1,2 Hui He, MD,1 Sangeeta R. Mehendale, MD, PhD,1,2 Chong-Zhi Wang, PhD,1,2 and Chun-Su Yuan, MD, PhD1,2,31 Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL, USA. 2Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA. 3Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL, USA.
Abstract
Purpose The pharmacological activities, notably the anticancer properties, of bioactive constituents fromfresh American ginseng berry have not yet been well studied. In this study, we investigated the antiproliferative effects of fresh American ginseng berry extract (AGBE) and its representative triterpenoid glycosides using the human colorectal cancer cell line SW480.
Materials and Methods Using high performance liquid chromatography (HPLC), the contents of 8 ginsenosides in AGBE were determined. The cell growth inhibitory effects of AGBE and three triterpenoid glycosides (ginsenosides Rb3, Re, and Rg3) were evaluated by proliferation assay and 3H-thymidine incorporation assay. Cell cycle and apoptotic effects were analyzed by using flow cytometry after staining with propidium iodide and annexin V
.Results HPLC analysis data showed that AGBE has a distinct ginsenoside profile. AGBE inhibited SW480 cell growth significantly in a time-dependent (24-96 hours) and concentration-dependent (0.1-1.0 mg/mL) manner. Ginsenosides Rb3, Re, and Rg3 also possess significant antiproliferative activities on SW480 cells. 3H-thymidine incorporation assay indicated that AGBE and ginsenosides Rb3, Re, and Rg3 might inhibit the transferring and duplication of DNA in SW480 cells. Flow cytometric assay data suggested that AGBE arrested SW480 cells in S and G2/M phases, and significantly induced cell apoptosis.
Conclusion AGBE and ginsenosides Rb3, Re, and Rg3 possessed significant antiproliferative effects and induced changes of morphological appearance on SW480 cells. The mechanisms of the antiproliferation of AGBE and tested ginsenosides involved could be cell cycle arrest and induction of apoptosis.
Role of cyclin inhibitor protein p21 in the inhibition of HCT116 human colon cancer cell proliferation by American ginseng (Panax quinquefolius) and its constituents M.L. King* and L.L. Murphy Southern Illinois University, School of Medicine, Department of Physiology, Carbondale, IL 62901
American ginseng and its ginsenoside constituents have been shown to exert anti-cancer effects although the mechanism of action remains unclear. The present study determined the effects of water-extracted ginseng (GE) or its ginsenoside (GF) and polysaccharide (PS) fractions on the proliferation of human colon cancer cells and examined the role of p21 in mediating these effects using wild-type and p21−/− HCT116 human colon carcinoma cells. Proliferation was inhibited by GE, GF, and PS in wild-type and p21−/− cells, and the p21−/− cells were more sensitive to these treatments. Wild type cells treated with GE were arrested in the G0/G1 phase of the cell cycle and the expression of p53 and p21 proteins was increased while phospho-MEK levels decreased. In contrast, cells deficient in p21 displayed reduced cell viability, elevated number of dead cells, and increased expression of Bax and cleaved caspase-3 proteins. Both polysaccharides and ginsenosides appear to be responsible for the anti-proliferative and proapoptotic effects of GE. This study suggests that p21 functions to arrest HCT116 wild-type cells treated with GE, while p21-deficient cells undergo cell death in a ginseng constituent-dependent manner.
Chemistry and Cancer Preventing Activities of Ginseng Saponins and Some Related Triterpenoid Compounds Shoji Shibata Shibata Laboratory of Natural Medicinal Materials c/o Minophagen Pharmaceutical Co. Ltd., Tokyo, Japan
More than 25 dammarane-type tetracyclic triterpenoid saponins have been isolated from ginseng, the root and rhizome of Panax ginseng C.A. Meyer (Araliaceae). The genuine sapogenins of those saponins, 20(S)-protopanaxa-diol and -triol, were identified as 20(S) 12 -hydroxy-and 20(S) 6 ,12 -dihydroxy-dammarenediol-II, respectively. There are two types of preparations from ginseng: white ginseng prepared by drying after peelling off and red ginseng prepared by steaming and drying. Some partly deglycosylated saponins such as ginsenoside Rh-1, Rh-2, and Rg-3 are obtained from red ginseng as artifacts produced during steaming. Several workers studied the metabolic transformation by human intestinal bacteria after oral administration of ginsenoside Rb-1 and Rb-2 and found that the stepwise deglycosylation yielded compound K and finally 20(S)-protopanaxadiol. Ginsenoside Rg-1was converted into 20(S)-protopanaxatriol via ginsenoside Rh-1. Yun et al. in Korea conducted the epidemiological case-control studies of ginseng and suggested its cancer preventing activities. Kitagawa et al. demonstrated in vitro that ginsenosides,especially 20(R)-ginsenoside Rg-3, specifically inhibited cancer cell invasionand metastasis. Azuma et al. found that ginsenoside Rb-2 inhibited tumor angiogenesis, and Kikuchi et al. reported that ginsenoside Rh-2 inhibited the human ovarian cancer growth in nude mice. Recently, ginsenoside Rg-3 was produced as an anti-angiogenic anti-cancer drug in China. The aforementioned reports suggest that less glycosylated protopanaxadiol derivatives are effective in cancer prevention. Apart from Ginseng tetracyclic triterpenoid saponins, some oleanane-type pentacyclic triterpenoid compounds showed the anti-carcinogenic activity in the two-stage anti-cancer-promotion experiments in vitro and in vivo.
....Anti-tumor activities are the properties characteristic not only to Ginseng saponins but also to other pentacyclic triterpenes.It is noteworthy, however, that ginsenosides, tetracyclic dammarane-type triterpenoid saponins, could be applied safely due to their mostly non-toxic and non-hemolytic characteristics. Ginseng has been employed in Chinese medicine and folklore medicine in the Eastern Asia regions without any noticeable side effects for more than 2000 yr. Apart from triterpenoid saponins in ginseng, acetylenic alcohol obtained from Ginseng, especially panaxytriol, showed anti-cancer activity against melanoma B16 when intramuscularly administered
Source : J Korean Med Sci 2001; 16(Suppl): S28-37 ISSN 1011-8934 Link to Full Article
Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells Ding-Fung Toh , Dhavalkumar Narendrabhai Patel , Eric Chun-Yong Chan , Alvin Teo , Soek-Ying Neo and Hwee-Ling Koh
Background Panax notoginseng is a potential source of anticancer compounds. This study aims to investigate the effects of steaming on the chemical profile of P. notoginseng and the anti-proliferative effects of P. notoginseng on liver cancer cells.
Methods Samples of powdered raw P. notoginseng roots were steamed for various durations. Extracts of the raw and steamed samples were subjected to ultra-high pressure liquid chromatography / mass spectrometry (UHPLC-MS) analysis for chemical profiling. The anti-proliferative effects on three human liver cancer cells, namely SNU449, SNU182 and HepG2, were evaluated using colorimetric WST-1 assay.
Results Steaming changed chromatographic and pharmacological profiles of P. notoginseng, causing differences in activities such as inhibition of cancer growth. Steamed P. notoginseng exhibited greater anti-proliferative effects against liver cancer cells (SNU449, SNU182 and HepG2) than its raw form; steaming up to 24 hours increased bioactivities. Steaming increased the concentrations of ginsenoside Rh2, Rk1, Rk3 and 20S-Rg3 and enhanced growth inhibition of liver cancer cells. Conclusion Steaming changes the chemical profile as well as anti-cancer biological activities of P. notoginseng. Steamed P. notoginseng contains potential compounds for the treatment of liver cancer.
Source : Chinese Medicine 2011, 6:4doi:10.1186/1749-8546-6-4 Link to Full Article
Anti-cancer and potential chemopreventive actions of ginseng by activating Nrf2 anti-oxidative stress/anti-inflammatory pathways
Constance Lay-Lay Saw, Qing Wu and Ah-Ng Tony Kong
Abstract This article review recent basic and clinical studies of ginseng, particularly the anti-cancer effects and the potential chemopreventive actions by activating the transcriptional factor, Nuclear factor (erythroid-derived 2)-like 2 factor 2 (Nrf2) anti-oxidative stress / anti-inflammatory pathways. Nrf2 is a novel target for cancer prevention as it regulates the antioxidant responsive element (ARE), a critical regulatory element in the promoter region of genes encoding cellular phase II detoxifying and anti-oxidative stress enzymes. The studies on the chemopreventive effects of ginseng or its components/products showed that Nrf2 could also be a target for ginseng's actions. A number of papers also demonstrated the anti-inflammatory effects of ginseng which could be related to the Nrf2 signalling pathway. Targeting Nrf2 pathway is a novel approach to the investigation of ginseng's cancer chemopreventive actions, including some oxidative stress / inflammatory conditions responsible for the initiation, promotion and progression of carcinogenesis.
Background Ginseng protects the cardiovascular system, stimulates the central nervous system [1] and possesses anti-cancer activities [2, 3] inhibiting human gastric adenocarcinoma [4] and human breast carcinoma [5]. Therefore, ginseng is a potential cancer preventive agent [6].11
Clinical studies on ginseng as adjuvant therapy for cancer Ginseng possesses preventive and therapeutics effects on cancer [14][15]. Ginseng is used to treat cancer or to reinforce the effects and/or reduce the side effects of chemotherapy [16][17]. Ginseng polysaccharides and ginsenosides are the main ingredients contributing to anti-cancer action of ginseng [18][19][20][21]. Ginseng boosts the patient’s immunity, suppresses the proliferation of tumour cells, inhibits the formation of new blood vessels in tumours, induces apoptosis of tumour cells, anti-metastasis of tumour and immunomodulation [3, 6].
Conclusion The anti-cancer and chemopreventive actions of ginseng could be exerted through activating the Nrf2 anti-oxidative and anti-inflammatory pathways. Further studies on the effects of ginseng in Nrf2-mediated induction of phase II/antioxidant enzymes would elucidate the action mechanism of ginseng in cancer chemoprevention
Source: Chinese Medicine 2010, 5:37 doi:10.1186/1749-8546-5-37 LINK TO FULL ARTICLE