Ginsenoside Re: pharmacological effects on cardiovascular system.

Ginsenosides are the bioactive constituents of ginseng, a key herb in traditional Chinese medicine. As a single component of ginseng, ginsenoside Re (G-Re) belongs to the panaxatriol group. Many reports demonstrated that G-Re possesses the multifaceted beneficial pharmacological effects on cardiovascular system. G-Re has negative effect on cardiac contractility and autorhythmicity. It causes alternations in cardiac electrophysiological properties, which may account for its antiarrhythmic effect. In addition, G-Re also exerts antiischemic effect and induces angiogenic regeneration. In this review, we first outline the chemistry and the pharmacological effects of G-Re on the cardiovascular system.

In vitro and in vivo anticancer effects of American ginseng berry: exploring representative compounds.

Panax ginseng roots, including the steamed roots, have been demonstrated to possess anticancer properties. However, there have been limited published studies on the cancer preventive effects of American ginseng. In this study, the in vitro and in vivo anti-colorectal cancer effects of American ginseng berry extracts, and their representative bioactive compounds were evaluated. The ginsenoside content in unsteamed American ginseng berry extract (AGE) and steamed berry extract (S-AGE) were determined by HPLC. In comparison to AGE, S-AGE showed significantly stronger antiproliferative effects on HCT-116, SW-480 and HT-29 human colorectal cancer cells. Antiproliferative effects of representative constituents in AGE and S-AGE, ginsenosides Rb3 and Rg3, were also evaluated, showing that Rg3 had a positive effect. Using flow cytometric analyses, we found that S-AGE arrests cancer cells in G1-phase and significantly induces cell apoptosis. Using xenograft mice, we conducted an in vivo antitumor study using S-AGE after HCT-116 cell inoculation. We observed that 50 mg/kg of S-AGE showed significant antitumor effects. Our results suggested that S-AGE inhibited the colorectal cancer growth both in vitro and in vivo, and this inhibition might be achieved through cell cycle arrest and induced apoptosis in the cells.

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.

Anti-diabetic effect of American ginseng may not be linked to antioxidant activity: comparison between American ginseng and Scutellaria baicalensis using an ob/ob mice model.

Antioxidants have been considered as a useful remedy in diabetes therapeutics, and thus, herbal medicines with antioxidant properties may play major role in treating diabetes. In this report, we performed a comparative study using American ginseng and Scutellaria baicalensis to test whether the anti-diabetic effect of American ginseng is associated with its antioxidant activity. We used a simple water extraction procedure to prepare American ginseng root extract (AGE) and S. baicalensis extract (SbE), and utilized these two antioxidant herbs to evaluate their anti-diabetic effect in obese diabetic ob/ob mice. HPLC analysis was used to identify major constituents in the AGE and SbE. After 12 days of daily intraperitoneal injection, AGE at 300 mg/kg showed significant effects on fasting blood glucose levels (P<0.01) and glucose tolerance test (P<0.01) compared to vehicle-treated mice. Animal body weights also reduced significantly after 12-day treatment (P<0.01). However, SbE, a very strong antioxidant extract, administered at 5-50 mg/kg (based on our previous studies without adverse events) for 12 days did not show any significant effects on blood glucose and body weight changes. No effects were shown when baicalein, an effective antioxidant constituent in SbE, was administered at 1-5 mg/kg. It appears that the anti-diabetic effect of American ginseng may not be linked to its antioxidant actions. The mechanisms of American ginseng's effects on reducing high blood glucose levels and body weight remain to be investigated in future experiments.

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.

Scutellaria baicalensis and a constituent flavonoid, baicalein, attenuate ritonavir-induced gastrointestinal side-effects.

Ritonavir, a protease inhibitor drug, is commonly used in AIDS therapy. As with other chemotherapeutic drugs that cause gastrointestinal adverse effects, ritonavir treatment is associated with significant nausea and vomiting. This study investigated whether Scutellaria baicalensis, and its active flavonoid constituent, baicalein, attenuate the gastrointestinal effects of ritonavir. The effects of herb administration were evaluated in ritonavir-treated rats using a rat pica model, which simulates nausea and vomiting in humans. The effects of herb administration on gastric emptying in rats were also measured. Ritonavir treatment resulted in increased kaolin intake or severe pica, the intensity of which was reduced significantly with S. baicalensis administration (1 mg kg(-1); P<0.05). High-performance liquid chromatography analysis of S. baicalensis showed the presence of an extremely potent flavonoid constituent, baicalein. The study aimed to determine if baicalein contributed to the anti-pica effect of the extract. It was observed that baicalein dose-dependently decreased pica in ritonavir-treated rats (P<0.001). In addition to inducing pica, ritonavir also significantly delayed gastric emptying, which could contribute to ritonavir-induced gastrointestinal dysfunction. When S. baicalensis extract was administered to ritonavir-treated rats the delayed gastric emptying was significantly attenuated (P<0.05). The results suggest that S. baicalensis and the constituent baicalein reduce the gastrointestinal dysfunction caused by ritonavir. It is concluded that S. baicalensis may potentially have a role to play in reducing drug-induced adverse effects.

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.

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.

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.

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.

Curry leaf (Murraya koenigii Spreng.) reduces blood cholesterol and glucose levels in ob/ob mice.

We observed that curry leaf (Murraya koenigii) extract possesses the property to decrease blood cholesterol and blood glucose levels in diabetic ob/ob mice. Mice received daily intraperitoneal injections of 80 mg/kg curry leaf extract for 10 consecutive days. The extract significantly decreased blood cholesterol level from 277.6 +/- 16.6 mg/d (day 0) to 182.0 +/- 15.3 mg/d (day 10, p < 0.01 compared with the change in vehicle group). The extract also significantly decreased blood glucose level from 387.0 +/- 15.6 mg/dl (day 0) to 214.0 +/- 26.6 mg/dl (day 10, p < 0.01). In addition, body weight was reduced after extract treatment. Our data suggest that curry leaf may be proved to be of clinical importance in improving the management of high cholesterol level and type 2 diabetes.

Scutellaria baicalensis decreases ritonavir-induced nausea.

BACKGROUND: Protease inhibitors, particularly ritonavir, causes significant gastrointestinal disturbances such as nausea, even at low doses. This ritonavir-induced nausea could be related to its oxidative stress in the gut. Alleviation of drug-induced nausea is important in effectively increasing patients' compliance and improving their quality of life. Conventional anti-emetic drugs can only partially abate the symptoms in these patients, and their cost has also been a concern. Rats respond to nausea-producing emetic stimuli by increasing consumption of non-nutritive substances like kaolin or clay, a phenomenon known as pica. In this study, we used this rat pica model to evaluate the effects of Scutellaria baicalensis, a commonly used oriental herbal medicine, on ritonavir-induced nausea. RESULTS: Rats treated with 20 mg/kg ritonavir significant caused increases of kaolin consumption at 24 to 48 hr (P < 0.01). Pretreatment with 0.3 and 3 mg/kg Scutellaria baicalensis extract significantly decreased ritonavir-induced kaolin intake in a dose-related manner (P < 0.01). Compared to vehicle treatment, the extract completely prevented ritonavir-induced kaolin consumption at dose 3 mg/kg. The area under the curves (AUC) for kaolin intake from time 0 to 120 hr for vehicle only, ritonavir only, SbE 0.3 mg/kg plus ritonavir, and SbE 3 mg/kg plus ritonavir were 27.3 g x hr, 146.7 g x hr, 123.2 g x hr, and 32.7 g x hr, respectively. The reduction in area under the curves of kaolin intake from time 0 to 120 hr between ritonavir only and SbE 0.3 mg/kg plus ritonavir, ritonavir only and SbE 3 mg/kg plus ritonavir were 16.0% and 77.7%, respectively. CONCLUSION: Scutellaria baicalensis significantly attenuated ritonavir-induced pica, and demonstrated a potential in treating ritonavir-induced nausea.

Antihyperglycemic effects of total ginsenosides from leaves and stem of Panax ginseng.

AIM: The antihyperglycemic effects of the total ginsenosides in Chinese ginseng (TGCG), extracted from leaves and the stem, were evaluated in diabetic C57BL/6J ob/ob mice. METHODS: Animals received daily intraperitoneal injections of TGCG (100 and 200 mg/kg) or oral administration (150 and 300 mg/kg) for 12 d. Fasting blood glucose levels and body weight were measured after fasting the animals for 4 h. Peripheral glucose use was also measured using an intraperitoneal glucose tolerance test. RESULTS: In the injection group, a high dose of TGCG (200 mg/kg) significantly lowered the fasting blood glucose levels in ob/ob mice on d 12 (153+/-16 mg/dL vs 203+/-9.8 mg/dL, P<0.01, compared to vehicle-treated group). In the oral group, blood glucose decreased notably with a dose of TGCG (300 mg/kg) on d 12 (169.1+/-12.6 mg/dL vs 211.6+/-13.8 mg/dL, P<0.05, compared to the vehicle-treated group). Glucose tolerance was also improved markedly in ob/ob mice. Furthermore, a significant reduction in bodyweight (P<0.05) was observed after 12 d of TGCG (300 mg/kg) treatment in mice from the oral group. CONCLUSION: The results indicated that in a diabetic ob/ob mouse model TGCG was endowed with significant anti-hyperglycemic and anti-obesity properties. Therefore, the total ginsenosides extracted from Chinese ginseng leaves and the stem may have some potential for treating diabetes.

Ginseng and diabetes.

Ginseng is a well-known medicinal plant used in traditional Oriental medicine. In recent decades, ginseng root has gained popularity as a dietary supplement in the United States. Ginseng has also been commonly used in Oriental medicine to treat diabetes-like conditions. The present review discusses the research on the anti-diabetic effects of ginseng and the possible mechanisms of its anti-diabetic actions.

American ginseng berry extract and ginsenoside Re attenuate cisplatin-induced kaolin intake in rats.

PURPOSE: Cisplatin, a chemotherapeutic agent, causes significant nausea and vomiting. It is postulated that cisplatin-induced oxidant stress may be responsible for these symptoms. We tested whether pretreatment with American ginseng berry extract (AGBE), an herb with potent antioxidant capacity, and one of its active antioxidant constituents, ginsenoside Re, could counter cisplatin-induced emesis using a rat pica model. METHODS: In rats, exposure to emetic stimuli such as cisplatin causes significant kaolin intake, a phenomenon called pica. We therefore measured cisplatin-induced kaolin intake as an indicator of the emetic response. Rats were pretreated with vehicle, AGBE (dose range 50-150 mg/kg, IP) or ginsenoside Re (2 and 5 mg/kg, IP). Rats were treated with cisplatin (3 mg/kg, IP) 30 min later. Kaolin intake, food intake, and body weight were measured every 24 h for 120 h. Additionally, the free radical scavenging activity of AGBE was measured in vitro using ESR spectroscopy. RESULTS: A significant dose-response relationship was observed between increasing doses of pretreatment with AGBE and reduction in cisplatin-induced pica. Kaolin intake was maximally attenuated by AGBE at a dose of 100 mg/kg. Food intake also improved significantly at this dose (P<0.05). Pretreatment with ginsenoside Re (5 mg/kg) also decreased kaolin intake (P<0.05). In vitro studies demonstrated a concentration-response relationship between AGBE and its ability to scavenge superoxide and hydroxyl radicals. CONCLUSION: Pretreatment with AGBE and its major constituent, Re, attenuated cisplatin-induced pica, and demonstrated potential for the treatment of chemotherapy-induced nausea and vomiting. Significant recovery of food intake further strengthens the conclusion that AGBE may exert an antinausea/antiemetic effect.

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.

Antioxidant effects of American ginseng berry extract in cardiomyocytes exposed to acute oxidant stress.

It is postulated that antioxidant properties of American ginseng root mediate its cardioprotective actions. The antioxidant capabilities of the American ginseng root have been demonstrated previously, however, the berry of the American ginseng has not yet been evaluated. In this study, we tested the American ginseng berry extract (AGBE) for its antioxidant effects in cell-free chemical systems using H(2)O(2)/FeSO(4) to generate hydroxyl radicals which were measured by a fluorescent probe, 2', 7'-dichlorofluorescin diacetate (DCFH/DA). Xanthine/xanthine oxidase was used to generate superoxide anion, which was measured by a fluorescent probe dihydroethidium (DHE). We found that AGBE decreased fluorescence significantly, suggesting that AGBE scavenges oxygen free radicals. We further tested whether AGBE (0.1-1 mg/ml) can protect cardiomyocytes from oxidative injury induced by exogenous or endogenous oxidants. Cells were exposed to either H(2)O(2) or antimycin A (a mitochondrial electron transport chain site III inhibitor that augments mitochondrial oxidant production). The resulting oxidant stress was measured using DCFH/DA and the cell death was assessed using propidium iodide staining. Pretreatment with AGBE (1 mg/ml) significantly attenuated DCF fluorescence by 49% or 85% and reduced cell death by 59% or 63% in cells exposed to H(2)O(2) or antimycin A, respectively. When the effects of extracts from berry and root of American ginseng were compared in cardiomyocytes exposed to antimycin A, we observed that AGBE conferred greater antioxidant protection at the same dose. We conclude that AGBE is a potent antioxidant that protects cardiomyocytes against oxidant-mediated injury and this protection is partly mediated by its free radical scavenging properties.