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Biomedical subjects

Sangeeta R Mehendale

Publications and source records attributed to Sangeeta R Mehendale.

13 recordsLinked to original sources

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.

Animals↗

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.

Antineoplastic Agents↗

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.

Animals↗

Opioid-induced gastrointestinal dysfunction.

Use of opioid analgesics is associated with a number of side effects, especially opioid-induced gastrointestinal dysfunction. The extensive use of these compounds and the significant negative impact of the resulting gastrointestinal dysfunction on patients' quality of life make it an important clinical issue. In recent years our understanding of the mechanisms of opioid-induced gastrointestinal dysfunction has advanced greatly. This article reviews the underlying pathophysiological mechanisms of specific gastrointestinal adverse effects of opioids. The role of endogenous opioid peptides in certain gastrointestinal diseases is also discussed. A better understanding of the pathophysiological mechanisms of opioid-induced bowel dysfunction should lead to the development of newer opioid analgesics and improved regimens resulting in reduced gastrointestinal adverse effects.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Analysis of Variance↗

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.

Animals↗

American ginseng leaf: ginsenoside analysis and hypoglycemic activity.

Previous studies showed that both American ginseng root and American ginseng berry extracts possess hypoglycemic properties. In this study, we investigated whether American ginseng leaves also have similar capabilities. We first analyzed the chemical constituents of American ginseng leaf and determined the content of six major ginsenosides, i.e., Rb(1), Rb(2), Rc, Rd, Re, and Rg(1), by high performance liquid chromatography (HPLC). Subsequently, we evaluated the hypoglycemic effect of American ginseng leaf extract (AGLE) in diabetic ob/ob adult mice. Animals received daily intraperitoneal injections of AGLE 50, 150 mg/kg or vehicle for 12 consecutive days. Fasting blood glucose levels, intraperitoneal glucose tolerance test (IPGTT), body weight and temperature were measured. On day 5, the 150 mg/kg AGLE group had significantly lower fasting blood glucose levels compared to vehicle-treated mice (223.0+/-13.9 mg/dl versus 258.0+/-14.0 mg/dl, P<0.05), while the blood glucose levels in 50 mg/kg group did not decrease significantly. On day 12, the glucose levels in both AGLE-treated groups were reduced significantly compared to vehicle group (180.0+/-10.0 mg/dl and 220.2+/-19.3 versus 268.0+/-10.0 mg/dl, P<0.01 and <0.05, respectively). IPGTT data showed that both AGLE 150 and 50 mg/kg groups significantly increased the glucose disposal on day 12 compared to the vehicle group. In addition, body weight decreased in ob/ob mice after AGLE treatment, and these body weight changes were accompanied by significant increases in body temperature (P<0.05). Our results suggest that AGLE possesses a significant anti-hyperglycemic and thermogenic activity and may prove to be beneficial in improving the management of type 2 diabetes.

Animals↗

Ephedra-containing dietary supplements in the US versus ephedra as a Chinese medicine.

Ephedra has been commonly used in traditional Chinese medicine (TCM) without significant adverse effects. Ephedra-containing dietary supplements are widely used in the United States to promote weight reduction and energy enhancement. However, there are significant safety concerns regarding the use of ephedra-containing dietary supplements, especially when such use occurs by consumers without medical supervision. This article reviews and contrasts the usage of ephedra as a dietary supplement in the US against an herbal medication in TCM. The potential adverse effects of ephedra-containing dietary supplements are also reviewed.

Adverse Drug Reaction Reporting Systems↗

Effects of antioxidant herbs on chemotherapy-induced nausea and vomiting in a rat-pica model.

Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting.

Animals↗

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.

Adult↗