Effects of Triterpenoid Glycosides from Fresh Ginseng Berry on SW480 Human Colorectal Cancer Cell Line.

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 (3)H-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. (3)H-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.

High performance liquid chromatographic analysis and anticancer potential of Oplopanax horridus: comparison of stem and berry extracts.

Oplopanax horridus or devil's club is a herbal medicine distributed in North America. The constituents and pharmacological activities of O. horridus (OPH) are largely unknown. In this study, we assayed OPH stem and berry extracts using high performance liquid chromatography (HPLC). The anticancer potentials of extracts on different human cancer cell lines (SW-480, HCT-116, HT-29, MCF-7 and NSCLC) were determined by MTS method. The effect of stem extract on cancer cell cycle, expression of cyclin A, and apoptosis were assayed using flow cytometry. HPLC data showed that the composition of OPH stem extract is more complicated than the berry extract. The wavelength of maximum absorption of the major constituent in stem and berry is 196.0 nm and 201.9 nm, respectively. Compared to the berry extract, the stem extract showed significant potent antiproliferative effect on all the studied cell lines. The stem extract at 0.1 mg/ml arrested cancer cells in S- and G2/M-phases, and significantly induced expression of cyclin A. After treatment with 0.1 mg/ml of stem extract for 72 h, apoptotic cells were increased to 45.2%, while control was 9.6%. The cell cycle arrest and induction of apoptosis may play a critical role in cancer chemoprevention by Oplopanax horridus stem extract.

Protease inhibitor-induced nausea and vomiting is attenuated by a peripherally acting, opioid-receptor antagonist in a rat model.

BACKGROUND: Protease inhibitors such as ritonavir can cause nausea and vomiting which is the most common reason for discontinuation. Rats react to nauseous and emetic stimuli by increasing their oral intake of non-nutritive substances like kaolin, known as pica behavior. In this study, we evaluated the effects of methylnaltrexone, a peripherally acting mu-opioid receptor antagonist that does not affect analgesia, on ritonavir-induced nausea and vomiting in a rat pica model. RESULTS: We observed that 24 to 48 hr after administration of oral ritonavir 20 mg/kg, kaolin consumption increased significantly in rats (P < 0.01). This increase was attenuated by pretreatment with an intraperitoneal injection of methylnaltrexone (0.3-3.0 mg/kg) in a dose dependent manner (P < 0.01) and also with naloxone (0.1-0.3 mg/kg) (P < 0.01). The areas under the curve for kaolin intake from time 0 to 120 hr were significantly reduced after administration of the opioid antagonists. Food intake was not significantly affected. Plasma naltrexone levels were measured after methylnaltrexone injection, and no detectable levels were found, indicating that methylnaltrexone was not demethylated in our experimental paradigm. CONCLUSION: These results suggest that methylnaltrexone may have potential clinical utility in reducing nausea and vomiting in HIV patients who take ritonavir.

Methylnaltrexone, a peripherally acting opioid receptor antagonist, enhances tumoricidal effects of 5-Fu on human carcinoma cells.

BACKGROUND: Methylnaltrexone, a novel peripherally acting opioid receptor antagonist, is used to treat opiate-induced constipation in cancer patients. Its effects on the activities of chemotherapeutic agents, however, have not been evaluated. In this study, the effect of methylnaltrexone on the action of 5-fluorouracil (5-FU) was tested in three human cancer cell lines. MATERIALS AND METHODS: Treatment was for 72 h and the effects on cell proliferation were measured in human SW-480 colorectal cancer cells, MCF-7 breast cancer cells and non-small cell lung cancer cells in vitro. The apoptotic effect was analyzed by using flow cytometry. The cell cycle and expression of cyclin A were assayed after staining with propidium iodide and cyclin A-fluorescein isothiocyanate. RESULTS: 5-FU decreased the cancer cell growth significantly in all three cancer cell lines in a concentration-dependent manner and methylnaltrexone enhanced the actions of 5-FU. Compared to 5-FU 10 muM alone on SW-480 cells (63.5+/-1.1%), on MCF-7 cells (58.3+/-3.1%), or on non-small cell lung cancer cells (81.3+/-1.6%), 5-FU 10 muM plus methylnaltrexone 1.0 muM reduced cancer cell growth in all three cell lines to 50.2+/-2.9% for SW-480 cells (p<0.05), 50.0+/-1.7% for MCF-7 cells (p<0.05) and 68.7+/-2.2% for lung cancer cells (p<0.01). Methylnaltrexone alone also showed anti-proliferative activity in the three cell lines. Methylnaltrexone at 1.0 muM, reduced SW-480 cell growth to 81.9+/-3.7% (p<0.01), MCF-7 cell growth to 85.9+/-2.4% (p<0.01) and lung cancer cell growth to 85.5+/-2.2% (p<0.01). Apoptosis was not induced by treatment of SW-480 cells with 1.0 or 10 muM methylnaltrexone for 48 h. However, methylnaltrexone increased the number of cells in the G(1)-phase and decreased the expression of cyclin A. CONCLUSION: At its therapeutic concentrations for opioid-induced constipation, methylnaltrexone does not attenuate and in fact may enhance the tumoricidal activity of 5-FU. Enhanced 5-FU activity may be attributed to the distinct pathways of 5-FU and methylnaltrexone, an effect that could give methylnaltrexone a complementary role in the treatment of cancer with chemotherapeutic agents.

Asian ginseng enhances the anti-proliferative effect of 5-fluorouracil on human colorectal cancer: comparison between white and red ginseng.

Previous studies showed that Asian ginseng, Panax ginseng C.A. Meyer, may have anti-cancer properties. However, there is limited data exploring the use of Asian ginseng as an adjuvant to chemotherapy, and minimal mechanistic studies related to their possible synergistic activities. In this study, the content of 8 ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1 and Rg3, in the extracts of white ginseng (WG) and red ginseng (RG) were determined by HPLC. Using HCT-116 human colorectal cancer cells, we compared the efficacy of WG and RG. We evaluated the synergy between ginseng and 5-fluorouracil (5-FU), and explored the mechanism of their anti-proliferative effects. As single extract, WG or RG used at concentrations of 0.1, 0.2 and 0.3 mg/mL, inhibited HCT-116 cell proliferation in a concentration-related manner. WG at 0.2 mg/mL did not show obvious synergy with 5-FU co-treatment, while RG at 0.2 and 0.3 mg/mL significantly enhanced the anti-proliferative effects of 5-FU at concentrations of 10, 50 and 100 microM (P < 0.05). Using flow cytometric assay, RG 0.3 mg/mL did not affect cancer cell apoptotic induction activity. However, the RG induced cell cycle arrest in the G1 phase, while 5-FU arrested the cell in the S phase. Different ginsenoside profiles are responsible for the observed differences in pharmacological effects. The effects of 8 ginsenosides on HCT-116 cells were assayed. Rd and Rg3 showed positive anti-proliferative effect. Our data suggested a potential for RG as an adjuvant therapy in the treatment of colorectal cancer, via a synergistic action.

Antiproliferative effects of different plant parts of Panax notoginseng on SW480 human colorectal cancer cells.

The chemical constituents and antiproliferative effects on SW480 human colorectal cancer cells of different plant parts of P. notoginseng were evaluated. The contents of saponins in extracts from root, rhizome, flower and berry of P. notoginseng were determined using high performance liquid chromatography. The contents and proportions of saponins were different among the four plant parts. Using the cell counting method, the antiproliferative effects were evaluated and the results indicated all four extracts, at 0.05-1.0 mg/mL, showed concentration-related antiproliferative effects on the cancer cells. The flower extract had stronger effects compared with the other three extracts; at 1.0 mg/mL, it inhibited the cell growth by 93.1% (p < 0.01). The antiproliferative effects of major saponins in notoginseng, notoginsenoside R1, ginsenosides Rb1, Rb3 and Rg1, were also evaluated, and the observed effects of major constituents support the pharmacological activities of extracts. The effects of notoginseng extracts on cell cycle and apoptosis of SW480 cells were determined using flow cytometry. Notoginseng extract can arrest the cells in S and G2/M phases. Remarkably apoptosis induction activities of notoginseng extracts were observed with the flower extract possessing the most potent effect, supporting the antiproliferative effect.

Antioxidant protection by American ginseng in pancreatic beta-cells.

Hyperglycemia in diabetic conditions may cause oxidative stress in pancreatic beta-cells, leading to their dysfunction and insulin resistance within peripheral tissues. Previous studies suggest that American ginseng berry extract may have hypoglycemic effects, as well as offer antioxidant protection. We examined effects of American ginseng berry extract and ginsenoside Re in a pancreatic beta-cell line, MIN-6, to determine if these two properties are related. Cells were exposed to oxidative stress via hydrogen peroxide incubation and oxidative stress was measured by oxidation of 2',7'-dichlorofluorescin diacetate. These cells showed a concentration-related response to hydrogen peroxide at 100-500 microM. In acute conditions where cells were treated with the extract for 10 min, we observed reduced oxidant injury suggesting direct scavenging effects. Chronic incubation of cells with the extract for 48 hours also demonstrated attenuation of oxidative stress. At high concentrations, Re showed a mild antioxidant effect in MIN-6 cells. Our insulin release observations also showed that the extract may help to increase insulin secretions from the cells. Our data suggest that the observed ability of ginseng to reduce blood glucose levels may be linked to its antioxidant effects on pancreatic beta-cells.

Chemopreventive effects of heat-processed Panax quinquefolius root on human breast cancer cells.

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 degrees 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.

Chemopreventive effects of Panax notoginseng and its major constituents on SW480 human colorectal cancer cells.

In this study, we evaluated the effects of Panax notoginseng root extract (NGRE) and its major constituents on SW480 human colorectal cancer cells. We used high performance liquid chromatography to determine the contents of major saponins in NGRE. The anti-proliferative effects were evaluated by the cell counting method, and concentration-related anti-proliferative effects were observed. At 1.0 mg/ml, NGRE inhibited cell growth by 85.8% (P<0.01), probably linked to the higher concentration of ginsenosides Rb1 and Rg1. The pharmacologic activities of notoginsenoside R1 and ginsenosides Rg1 and Rb1 on the cells were antiproliferative. We tested the effects of NGRE on DNA synthesis by measuring [3H]-thymidine incorporation. NGRE induced cell apoptosis at 0.5 and 1 mg/ml. Two-day treatment with 300 microM of notoginsenoside R1, ginsenosides Rg1 and Rb1 increased cell apoptosis significantly. Cell cycle and cyclin A assay showed that NGRE arrested cells in the synthesis phase and increased the expression of cyclin A remarkably. NGRE also enhanced the actions of two chemotherapeutic agents, 5-fluorouracil and irinotecan. Cell growth decreased more with the combined treatment of NGRE and 5-fluorouracil (or irinotecan) than with the chemotherapy agent applied alone, suggesting that notoginseng can reduce the dose of 5-fluorouracil (or irinotecan) needed to achieve desired effects. Further in vivo and human trials are warranted to test whether notoginseng is a valuable chemo-adjuvant with clinical validity.

Red American ginseng: ginsenoside constituents and antiproliferative activities of heat-processed Panax quinquefolius roots.

Red Asian ginseng ( Panax ginseng C. A. Meyer, Araliaceae) is used in many Oriental countries. In this study, the saponin constituents and anticancer activities of steamed American ginseng ( Panax quinquefolius L.) roots were evaluated. The contents of 12 ginsenosides in the roots were determined using high performance liquid chromatography (HPLC). After the steaming treatment (100 - 120 degrees C for 1 h and 120 degrees C for 0.5 - 4 h), the quantity of 7 ginsenosides decreased and that of 5 others increased. The content of ginsenoside Rg3, a previously recognized anticancer compound, increased significantly when the root was steamed at 120 degrees C for 0.5 - 3 h. The antiproliferative effects of unsteamed and steamed (120 degrees C for 1 h and 2 h) American ginseng root extracts were assayed by the modified trichrome stain (MTS) method using three cancer cell lines (SW-480, HT-29, NSCLC). Heat-processing increased the antiproliferative effect of American ginseng significantly, and the activity of the extract from roots steamed for 2 h was greater than that of roots steamed for 1 h. Chemical constituents and antiproliferative activities of white and red Asian ginseng have also been evaluated. Five representative ginsenosides, Rb1, Rd, Re, Rg2 and Rg3, were studied. Ginsenoside Rg3 had the most potent effect. The antiproliferative activities of red American ginseng are augmented when ginsenoside Rg3 is increased.

Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells.

PURPOSE: Panax notoginseng is a commonly used Chinese herb. Although a few studies have found that notoginseng shows anti-tumor effects, the effect of this herb on colorectal cancer cells has not been investigated. 5-Fluorouracil (5-FU) is a chemotherapeutic agent for the treatment of colorectal cancer that interferes with the growth of cancer cells. However, this compound has serious side effects at high doses. In this study, using HCT-116 human colorectal cancer cell line, we investigated the possible synergistic anti-cancer effects between notoginseng flower extract (NGF) and 5-FU on colon cancer cells. METHODS: The anti-proliferation activity of these modes of treatment was evaluated by MTS cell proliferation assay. Apoptotic effects were analyzed by using Hoechst 33258 staining and Annexin-V/PI staining assays. The anti-proliferation effects of four major single compounds from NGF, ginsenosides Rb1, Rb3, Rc and Rg3 were also analyzed. RESULTS: Both 5-FU and NGF inhibited proliferation of HCT-116 cells. With increasing doses of 5-FU, the anti-proliferation effect was slowly increased. The combined usage of 5-FU 5 microM and NGF 0.25 mg/ml, significantly increased the anti-proliferation effect (59.4 +/- 3.3%) compared with using the two medicines separately (5-FU 5 microM, 31.1 +/- 0.4%; NGF 0.25 mg/ml, 25.3 +/- 3.6%). Apoptotic analysis showed that at this concentration, 5-FU did not exert an apoptotic effect, while apoptotic cells induced by NGF were observed, suggesting that the anti-proliferation target(s) of NGF may be different from that of 5-FU, which is known to inhibit thymidilate synthase. CONCLUSIONS: This study demonstrates that NGF can enhance the anti-proliferation effect of 5-FU on HCT-116 human colorectal cancer cells and may decrease the dosage of 5-FU needed for colorectal cancer treatment.

Cisplatin's tumoricidal effect on human breast carcinoma MCF-7 cells was not attenuated by American ginseng.

PURPOSE: We previously observed that American ginseng berry and ginsenoside Re attenuated cisplatin-induced emesis in a rat model, suggesting that the herb may have a value in treating chemotherapy-induced nausea/vomiting. However, it is not clear whether consuming ginseng concurrently with chemotherapy affects the efficacy of chemotherapeutic agents. In this study, we explored if the ginseng extract and its constituents, ginsenosides Rb1, Rb3, and Re, alter tumoricidal activity of cisplatin in human cancer cells. METHODS: Tumoricidal effects of cisplatin, and/or American ginseng berry extract (AGBE) and ginsenosides Rb1, Rb3, and Re, on human breast carcinoma MCF-7 cells were measured as cell proliferation in vitro. Cell counts were performed in MCF-7 cells pretreated with test agents for 72 h. RESULTS: Cisplatin decreased MCF-7 cell proliferation significantly in a concentration-dependent manner. Compared to control group, cisplatin reduced the cell proliferations to 56.5+/-3.3% at 1 microg/ml, to 36.6+/-2.4% at 5 microg/ml, and to 26.9+/-2.4% at 15 microg/ml (P<0.01). AGBE also inhibited the cell proliferation significantly, although in a less extended manner. When the berry extract at 0.5 mg/ml was used with cisplatin at 1 microg/ml, a significant enhancement of cisplatin's activity was observed (35.8+/-2.5%; P<0.05). We also observed that Rb1 did not change cisplatin's activity; Rb3, at a higher concentration, increased cisplatin's anti-proliferation activity (48.0+/-1.2%; P<0.05); Re increased cisplatin's activity (Re 0.1 mg/ml, 48.0+/-2.8%; Re 0.3 mg/ml, 31.9+/-2.2%, P<0.01). CONCLUSION: Our data suggest that AGBE and the tested ginsenosides do not attenuate cisplatin's tumoricidal activity in MCF-7 cells, but in fact may actually enhance it. Additionally, the ginseng extract and ginsenoside Re by themselves exerted anti-proliferative activity against MCF-7 cells. The herb might potentially serve a complementary role with the chemotherapeutic agents in treating cancer, in addition to decreasing chemotherapy-induced nausea/vomiting.

Steamed American ginseng berry: ginsenoside analyses and anticancer activities.

This study was designed to determine the changes in saponin content in American ginseng berries after treatment by heating and to assess the anticancer effects of the extracts. After steaming treatment (100-120 degrees C for 1 h, and 120 degrees C for 0.5-4 h), the content of seven ginsenosides, Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd, decreased; the content of five ginsenosides, Rh1, Rg2, 20R-Rg2, Rg3, and Rh2, increased. Rg3, a previously identified anticancer ginsenoside, increased significantly. Two hours of steaming at 120 degrees C increased the content of ginsenoside Rg3 to a greater degree than other tested ginsenosides. When human colorectal cancer cells were treated with 0.5 mg/mL steamed berry extract (120 degrees C 2 h), the antiproliferation effects were 97.8% for HCT-116 and 99.6% for SW-480 cells. At the same treatment concentration, the effects of unsteamed berry extract were 34.1% for HCT-116 and 4.9% for SW-480 cells. After staining with Hoechst 33258, apoptotic cells increased significantly by treatment with steamed berry extract compared with unheated extracts. Induction of apoptosis activity was confirmed by flow cytometry after staining with annexin V/PI. The steaming of American ginseng berries augments ginsenoside Rg3 content and increases the antiproliferative effects on two human colorectal cancer cell lines.

Chronic pretreatment with American ginseng berry and its polyphenolic constituents attenuate oxidant stress in cardiomyocytes.

The acute anti-oxidant and protective effect of American ginseng berry extract (AGBE) has been demonstrated in cultured cardiomyocytes in our previous study. In the current study we evaluated if a chronic pretreatment of cultured cardiomyocytes with AGBE can alter the cellular antioxidant potential. Chick embryo cardiomyocytes were treated with AGBE (0.5-2.5 mg/ml) for up to 72 h. The treated cells were then exposed to exogenously added hydrogen peroxide (H(2)O(2); 500 microM). The oxidant-mediated injury was measured using a fluorescent probe 2',7'-dichlorofluorescin diacetate (DCFH/DA) while cell death was measured using propidium iodide (PI) staining. The non-treated (control) cells exposed to H(2)O(2) showed significant increase in DCF- and PI-mediated fluorescence suggesting significant oxidative injury and cell death. Pretreatment with AGBE demonstrated a significant attenuation of DCF fluorescence (p<0.005) with AGBE 0.5 mg/ml showing a 17% decrease, AGBE 1.0 mg/ml showing a 26% decrease, and AGBE 2.5 mg/ml showing a 49% decrease from control DCF fluorescence following a 72 h pretreatment. Cell death caused by H(2)O(2) was also significantly attenuated in AGBE-pretreated cells in a concentration- and time-dependent manner (p<0.005). We also demonstrated that active polyphenolic constituents in AGBE, caffeic acid and chlorogenic acid, appear to contribute significantly to AGBE's protective effects. Finally, catalase inhibition resulted in a significantly increased fluorescence in AGBE-treated cells compared to the control. The results suggest that pretreatment with AGBE upregulates peroxide detoxifying mechanisms, which could affect intracellular oxidant dynamics in cardiomyocytes.

Effects of ganoderma lucidum extract on chemotherapy-induced nausea and vomiting in a rat model.

Chemotherapy is highly cytotoxic, causing a number of severe adverse effects such as nausea and vomiting. Herbal medicines, which can often be used on a daily basis for prolonged treatment, may be clinically beneficial. Ganoderma lucidum or Lingzhi mushroom has been recognized as a remedy in treating a number of medical conditions, including balancing immunity and decreasing drug-induced side effects. It has been shown that rats react to emetic stimuli, like the chemotherapy agent cisplatin, by increased consumption of kaolin, known as pica; and this rat model has been utilized to evaluate novel anti-emetic compounds. In this study, we evaluated the effects of a G. lucidum extract (SunRecome, the most commonly used Lingzhi mushroom extract in China) in attenuating cisplatin-induced nausea and vomiting in the rat pica model. We observed that intraperitoneal cisplatin injection caused a significant increase in kaolin intake at 24, 48, 72 and 96 hours, reflecting cisplatin's nausea and vomiting action. This cisplatin-induced kaolin intake dose-dependently decreased after 1, 3 and 10 mg/kg G. lucidum extract injection (p < 0.01). In addition, there was a significant reduction of food intake after cisplatin. The cisplatin-induced food intake reduction improved significantly after G. lucidum extract administrations in a dose-related manner (p < 0.01), suggesting a supportive effect of the extract on general body condition. Future controlled clinical trials are needed to evaluate the safety and effectiveness of this herbal medication.

Anti-diabetic effect of ginsenoside Re in ob/ob mice.

We evaluated the anti-diabetic effects of ginsenoside Re in adult male C57BL/6J ob/ob mice. Diabetic ob/ob mice with fasting blood glucose levels of approximately 230 mg/dl received daily intraperitoneal injections of 7, 20 and 60 mg/kg ginsenoside Re for 12 consecutive days. Dose-related effects of ginsenoside Re on fasting blood glucose levels were observed. After the 20 mg/kg treatment, fasting blood glucose levels were reduced to 188+/-9.2 and 180+/-10.8 mg/dl on Day 5 and Day 12, respectively (both P<0.01 compared to vehicle group, 229+/-9.5 and 235+/-13.4 mg/dl, respectively). The EC(70) of ginsenoside Re was calculated to be 10.3 mg/kg and was used for subsequent studies. Consistent with the reduction in blood glucose, there were significant decreases in both fed and fasting serum insulin levels in mice treated with ginsenoside Re. With 12 days of ginsenoside treatment, glucose tolerance of ob/ob mice increased significantly, and the area under the curve for glucose decreased by 17.8% (P<0.05 compared to vehicle treatment). The hypoglycemic effect of the ginsenoside persisted even at 3 days of treatment cessation (blood glucose levels: 198+/-13.1 with ginsenoside treatment vs. 253+/-20.3 mg/dl with vehicle, P<0.01). There were no significant changes in body weight or body temperature. Preliminary microarray analysis revealed differential expression of skeletal muscle genes associated with lipid metabolism and muscle function. The results suggest that ginsenoside Re may prove to be useful in treating type 2 diabetes.

Polyphenol contents in grape-seed extracts correlate with antipica effects in cisplatin-treated rats.

BACKGROUND: Grape-seed (Vitis spp.) extract (GSE) is a widely used antioxidant dietary supplement. Chemotherapeutic agents such as cisplatin induce oxidative damage in the gastrointestinal tract and cause nausea and vomiting. MATERIALS AND METHODS: A rat model of simulated emesis was used to observe that cisplatin significantly increased kaolin consumption (or pica). Three GSEs from different sources were used in this study. RESULTS: High-performance liquid chromatographic analysis of five major constituents (gallic acid, catechin, epicatechi, procyanidin B2, and epicatechin gallate) revealed that each constituent had different levels in the three GSEs. Extract #1, prepared in the laboratory of the investigators, had the lowest total polyphenol content (27.27 mg/g); Extract #2, obtained from a dietary supplement company in the United States, had a somewhat higher level (35.84 mg/g); and Extract #3, obtained from China, had the highest level (194.21 mg/g). Subsequently these GSEs were intraperitoneally administered in rats to evaluate their ability to decreasing cisplatin induced pica. At 10 mg/kg all three GSEs, with varying degrees of effect, decreased cisplatin-induced pica. The areas under the curves of kaolin intake from time 0 to 72 hours, compared to those in the cisplantin-only group, were reduced 45% for Extract #1 (p < 0.01), 54% for Extract #2 (p < 0.01), and 66% Extract #3 (p < 0.001). CONCLUSIONS: The study data showed variable polyphenol contents and proportions in the three GSEs correlated to variable pharmacologic effects, indicating the importance of standardization of herbal product preparations. However further increasing of the GSE doses reversed the antipica effects of GSEs, probably because of their pro-oxidant effects. Results from this study suggest that an appropriate dose of GSE has therapeutic value in treating cisplatin-induced emesis.

Effects of Corydalis yanhusuo and Angelicae dahuricae on cold pressor-induced pain in humans: a controlled trial.

Pain is considered the most common complaint worldwide for which patients seek treatment. Conventional analgesic agents play an important role in modern pain therapy, but they cause several adverse effects. Therefore, newer and better analgesics continue to be investigated. In this controlled clinical trial, the authors evaluated the analgesic effects of 2 herbal medicines, Corydalis yanhusuo and Angelicae dahuricae. They used the cold-pressor test-a simple, reliable, and widely used model in humans-for induction of tonic pain. They demonstrated that after a single, oral administration of the extracts of C. yanhusuo and A. dahuricae, the pain intensity and pain bothersomeness scores significantly decreased (both P < .01). Dose-related analgesic effect was also observed. Results from this study suggest that C. yanhusuo and A. dahuricae may have a potential clinical value for treating mild to moderate pain.

Alternative therapies for male and female sexual dysfunction.

Sexual dysfunction is prevalent in both men and women. Although new pharmaceutical agents have been identified for male erectile problems, sexual desire and orgasm disorders, individuals with sexual dysfunction often seek alternative therapies, including traditional Chinese medicine. This article reviews currently used alternative therapies, such as herbal medications, L-arginine, acupuncture, biofeedback and others. Potential herb-drug interactions are also presented.

Methylnaltrexone prevents morphine-induced kaolin intake in the rat.

Opioids are frequently used analgesics, and emesis is a common opioid-induced adverse effect. Methylnaltrexone, a peripheral opioid antagonist, has the potential to block the undesired effects of opioids that are mediated by peripheral receptors while sparing the analgesic effect. We used a rat model of simulated emesis or pica to study if methylnaltrexone decreases morphine induced-kaolin consumption. We observed that after morphine administration, kaolin intake increased significantly compared to intake in the vehicle group, and the increase could be attenuated by ondansetron administration. Methylnaltrexone dose-dependently reduced kaolin ingestion induced by morphine. Morphine and methylnaltrexone did not significantly affect food intake and body weight in the experimental animals. Our data suggest that methylnaltrexone has therapeutic value in treating opioid-induced nausea and vomiting.