Steamed Ginger May Enhance Insulin Secretion through KATP Channel Closure in Pancreatic ß-Cells Potentially by Increasing 1-Dehydro-6-Gingerdione Content.

Ginger (Zingiber officinale Roscoe) and its active compounds (gingerols, shogaols and paradols) have been reported as having beneficial functions for several diseases, including diabetes. In this study, we revealed that the steaming process could enhance the anti-diabetic potential of ginger. To confirm the anti-diabetic effect of steamed ginger extract (GG03), we assessed pancreatic islets impaired by alloxan in zebrafish and demonstrated anti-hyperglycemic efficacy in a mouse model. The EC50 values of ginger extract (GE) and GG03 showed that the efficacy of GG03 was greater than that of GE. In addition, LC50 values demonstrated that GG03 had lower toxicity than GE, and the comparison of the Therapeutic Index (TI) proved that GG03 is a safer functional food. Furthermore, our data showed that GG03 significantly lowered hyperglycemia in a diabetic mouse model. HPLC was performed to confirm the change in the composition of steamed ginger. Interestingly, GG03 showed a 375% increase in 1-dehydro-6-gingerdione (GD) compared with GE. GD has not yet been studied much pharmacologically. Thus, we identified the protective effects of GD in the damaged pancreatic islets of diabetic zebrafish. We further assessed whether the anti-diabetic mechanism of action of GG03 and GD involves insulin secretion. Our results suggest that GG03 and GD might stimulate insulin secretion by the closure of KATP channels in pancreatic ß-cells.

Evaluación de la bioactividad de plantas medicinales cultivadas en el Perú usando la prueba de letalidad de Artemia salina / Bioactivity of medicinal plants cultivated in Peru using Artemia salina lethality test

Objetivo. Determinar la bioactividad de trece plantas medicinales peruanas a través de su capacidad citotóxica. Materiales y métodos. Se elaboraron extractos acuosos, hidroalcohólicos, o zumos liofilizados de las especies vegetales seleccionadas. La citotoxicidad in vitro fue evaluada usando la prueba de letalidad de Artemia salina, con la determinación de la concentración letal media (CL50). El potencial citotóxico de las muestras de extractos evaluados, se clasificaron en: a) no tóxico: CL50 > 1000 µg/ mL; b) baja toxicidad: 500 < CL50 ≤ 1000 µg/ mL; c) toxicidad moderada: 100 < CL50 ≤ 500 µg/ mL, y d) alta toxicidad: CL50 < 100 µg/ mL. Resultados. Los diferentes extractos del rizoma de Curcuma longa mostraron una potente actividad citotóxica, con CL50 entre 20,67 ± 7,04 y 98,14± 2,64 ug/mL. Los extractos de rizoma de Zingiber officinale, del fruto de Physalis angulata y la planta entera de Physalis angulata también mostraron actividad citotóxica con CL50 de 87,15±18,17, 323,48±18,85 y 328,92±23,08 ug/mL, respectivamente. Conclusión. Se encontró actividad citotóxica en los extractos de los rizomas de Curcuma longa, Zingiber officinale, así como el fruto y planta entera de Physalis angulata. Futuros estudios podrán determinar si la flora cultivada en el Perú puede ser una fuente para el desarrollo futuro de agentes antitumorales.

Objective. To determine the bioactivity of 13 Peruvian medicinal plants through their cytotoxic capacity. Material and methods. Aqueous, hydroalcoholic extracts or lyophilized juices of the selected plant species were elaborated. In vitro cytotoxicity was evaluated using the Artemia salina lethality test, with the determination of the mean lethal concentration (LC50). The cytotoxic potential of the samples of evaluated extracts was classified into: a) non-toxic: LC50> 1000 µg / mL, b) low toxicity: 500 < LC50 ≤ 1000 µg / mL, c) moderate toxicity: 100 < LC50≤ 500 µg / mL, and d) high toxicity: LC50 <100 µg / mL. Results. The different extracts of the Curcuma longa's rhizome showed a potent cytotoxic activity, with LC50 between 20.67 ± 7.04 and 98.14 ± 2.64 µg / mL. Zingiber officinale rhizome, Physalis angulate fruit and Physalis angulata whole plant extracts, also showed cytotoxic activity with LC50 of 87.15 ± 18.17, 323.48 ± 18.85 and 328.92 ± 23.08 µg / mL, respectively. Conclusion. Cytotoxic activity was found in the extracts of Curcuma longa, Zingiber officinale rhizomes, as well as Physalis angulata fruit and whole plant extracts. Future studies will be able to determine if the flora cultivated in Peru could be a source for future development of antitumoral agents.

Toxicological effects of pet food ingredients on canine bone marrow-derived mesenchymal stem cells and enterocyte-like cells.

We developed an in vitro method to assess pet food ingredients safety. Canine bone marrow-derived mesenchymal stem cells (BMSC) were differentiated into enterocyte-like cells (ELC) to assess toxicity in cells representing similar patterns of exposure in vivo. The toxicological profile of clove leave oil, eugenol, guanosine monophosphate (GMP), GMP + inosine monophosphate, sorbose, ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol and citric acid was assessed in BMSC and ELC. The LC50 for GMP + inosine monophosphate was 59.42 ± 0.90 and 56.7 ± 3.5 mg ml(-1) for BMSC and ELC; 56.84 ± 0.95 and 53.66 ± 1.36 mg ml(-1) for GMP; 0.02 ± 0.001 and 1.25 ± 0.47 mg ml(-1) for citric acid; 0.077 ± 0.002 and 0.037 ± 0.01 mg ml(-1) for cinnamaldehyde; 0.002 ± 0.0001 and 0.002 ± 0.0008 mg ml(-1) for thymol; 0.080 ± 0.003 and 0.059 ± 0.001 mg ml(-1) for thyme oil; 0.111 ± 0.002 and 0.054 ± 0.01 mg ml(-1) for cinnamon bark oil; 0.119 ± 0.0004 and 0.099 ± 0.011 mg ml(-1) for clove leave oil; 0.04 ± 0.001 and 0.028 ± 0.002 mg ml(-1) for eugenol; 2.80 ± 0.11 and 1.75 ± 0.51 mg ml(-1) for ginger root extract; > 200 and 116.78 ± 7.35 mg ml(-1) for sorbose. Lemon grass oil was evaluated at 0.003-0.9 in BMSC and .03-0.9 mg ml(-1) in ELC and its mechanistic effect was investigated. The gene toxicology studies showed regulation of 61% genes in CYP450 pathway, 37% in cholestasis and 33% in immunotoxicity pathways for BMSC. For ELC, 80% for heat shock response, 69% for beta-oxidation and 65% for mitochondrial energy metabolism. In conclusion, these studies provide a baseline against which differential toxicity of dietary feed ingredients can be assessed in vitro for direct effects on canine cells and demonstrate differential toxicity in differentiated cells that represent gastrointestinal epithelial cells.

Toxic potentials of ten herbs commonly used for aphrodisiac effect in Turkey.

BACKGROUND/AIM: Sexual dysfunction is a serious problem worldwide. In Turkey, herbal products are used by some people suffering from sexual dysfunction. Despite their therapeutic advantages, some constituents of herbs are potentially toxic and pose health risks because they can be bought from the market without a prescription. Therefore, we aimed to determine the safety of herbs possessing aphrodisiac effects, chosen on the basis of their frequency of medicinal use and commercial importance in Turkey. MATERIALS AND METHODS: Ten herbs (Anethum graveolens, Carthamus tinctorius, Citrus aurantium, Cocos nucifera, Glycyrrhiza glabra, Melissa officinalis, Nigella arvensis, Pinus pinea, Prunus mahaleb, and Zingiber officinale) were extracted with water, methanol, and chloroform. The cyto- and genotoxic potentials of the extracts were assessed using an MTT test on a rat kidney cell line and an Ames assay in Salmonella typhimurium strains, respectively. RESULTS: In the cytotoxic evaluation, IC50 values were 1.51-31.4 mg/mL for the methanol and chloroform extracts, while the water extracts were not cytotoxic. In the genotoxic evaluation, it was revealed that the water extracts had more mutagenic activity than the chloroform and methanol extracts. Water extract of M. officinalis was shown to have the most genotoxic activities to TA100 (±S9) and TA98 (-S9). CONCLUSION: These results might be useful in determining the toxic effects of herbs and lead to precautions being taken in regards to their consumption.

Safety assessment of potential food ingredients in canine hepatocytes.

This research aimed to develop in vitro methods to assess hazard of canine food ingredients. Canine hepatocytes were harvested and cell viability of clove-leaf oil (CLO), eugenol (EUG), lemongrass oil (LGO), guanosine monophosphate (GMP), inosine monophosphate (IMP), sorbose, ginger-root extract (GRE), cinnamon-bark oil (CBO), cinnamaldehyde (CINA), thymol oil (TO), thymol (THYM), and citric acid were assessed with positive controls: acetaminophen (APAP), aflatoxin B1 and xylitol. Molecular Toxicology PathwayFinder array (MTPF) analyzed toxicity mechanisms for LGO. LC50 for APAP was similar among human (3.45), rat (2.35), dog (4.26 mg/ml). Aflatoxin B1 had an LC50 of 4.43 (human), 5.78 (rat) and 6.05 (dog) µg/ml; xylitol did not decrease viability. LC50 of CLO (0.185 ± 0.075(SD)), EUG (0.165 ± 0.112), LGO (0.220 ± 0.012), GRE (1.54 ± 0.31) mg/ml; GMP (166.03 ± 41.83), GMP + IMP (208.67 ± 15.27) mM; CBO (0.08 ± 0.03), CINA (0.11 ± 0.01), TO (0.21 ± 0.03), THYM (0.05 ± 0.01), citric acid (1.58 ± 0.08) mg/ml, while sorbose was non-toxic. LGO induced upregulation of 16 and down-regulation of 24 genes, which CYP and heat shock most affected. These results suggest that in vitro assays such as this may be useful for hazard assessment of food ingredients for altered hepatic function.

Safety and efficacy of Zingiber officinale roots on fertility of male diabetic rats.

The acute toxicity of methanolic and watery extracts of Zingiber officinale (ZO) roots in mice and their effects on fertility of male diabetic rats were carried out. The fertility experiment was done on six groups of male rats one of them was kept as normal control, while the others were rendered diabetic by subcutaneous injection of alloxan (120 mg kg(-1)). One group was left as diabetic control, while the others were given orally either methanolic (100 and 200 mg kg(-1)) or watery extract (150 and 300 mg kg(-1)) for 65 consecutive days. The results showed that no mortalities occur when both extracts were given orally to mice in doses up to 5 g kg(-1) b.wt. Both extracts increased fertility index, sexual organs weight, serum testosterone level and sperm motility and count. Histopathological examination of the testes of diabetic rats showed mild to moderate degenerative changes of spermatogenic cells, diffuse edema and incomplete arrest of spermatogenesis. Treatment with ZO extracts caused alleviation of the testicular lesions that appeared in non-treated diabetic rats. Conclusively, extracts of ZO have high safety in mice and intake of ZO roots as a drink may be useful for diabetic patients who suffer from sexual impotency.

Oral dose-ranging developmental toxicity study of an herbal supplement (NT) and gallic acid in rats.

OBJECTIVE: To evaluate the combination of rhubarb, astragalus, red sage, ginger, and turmeric (mixture referred to as "NT") together with gallic acid for evidence of reproductive toxicity in rats. METHODS: Fifty virgin female rats were cohabited with male rats. Day 0 of potential pregnancy was evidence of spermatozoa on vaginal smear. The presumably pregnant rats were randomized to five groups of 10 individuals and were fed by daily gavage on days 6-20 of presumed gestation with one of the following: deionized water placebo, 21.6 mg/kg per day, 215 mg/kg per day, 430 mg/kg per day, or 860 mg/kg per day of a mixture of NT (20%) and gallic acid (80%). Cesarean section was performed on day 21. RESULTS: All 50 rats had one or more live fetuses and survived until they were killed. Body weight was reduced in the 860 mg/kg per day group compared with placebo: mean (SD), 406.8 (23.0) vs. 430.1 (27.7) g, P<0.05. There were no dose-related adverse events or differences between groups in uterine size, food intake, corpora lutea, implantations, litter size, number of live fetuses, and gender distribution of fetuses or fetal resorptions. There were no dead fetuses, and all placentae appeared normal. All rats and tissues were normal at necropsy. Fetal weights did not differ between groups, and there were no fetal abnormalities. CONCLUSION: The combination of NT and gallic acid gave no evidence of reproductive toxicity at 430 mg/kg per day or below, which is reassuring should this combination be used in the future as a dietary herbal supplement for the treatment of obesity.

A 35-day gavage safety assessment of ginger in rats.

Ginger (Zingiber officinale Roscoe, Zingiberacae) is one of the most commonly used spices around the world and a traditional medicinal plant that has been widely used in Chinese, Ayurvedic and Unani-Tibb medicines for several thousand years. However, there was still lack of systemic safety evaluation. We conducted a 35-day toxicity study on ginger in rats. Both male and female rats were daily treated with ginger powder at the dosages of 500, 1000 and 2000 mg/kg body weight by a gavage method for 35 days. The results demonstrated that this chronic administration of ginger was not associated with any mortalities and abnormalities in general conditions, behavior, growth, and food and water consumption. Except for dose-related decrease in serum lactate dehydrogenase activity in males, ginger treatment induced similar hematological and blood biochemical parameters to those of controlled animals. In general, ginger treatment caused no overt organ abnormality. Only at a very high dose (2000 mg/kg), ginger led to slightly reduced absolute and relative weights of testes (by 14.4% and 11.5%, respectively). This study provides a new understanding of the toxicological properties of ginger.

Effect of ginger tea on the fetal development of Sprague-Dawley rats.

This study investigated the effect of ginger, a common morning sickness remedy, on fetal development. Pregnant Sprague-Dawley rats were administered, from gestation day 6 to 15, 20 g/liter or 50 g/liter ginger tea via their drinking water and then sacrificed at day 20. No maternal toxicity was observed, however embryonic loss in the treatment groups was double that of the controls (P<0.05). No gross morphologic malformations were seen in the treated fetuses. Fetuses exposed to ginger tea were found to be significantly heavier than controls, an effect that was greater in female fetuses and was not correlated with increased placental size. Treated fetuses also had more advanced skeletal development as determined by measurement of sternal and metacarpal ossification centers. The results of this study suggest that in utero exposure to ginger tea results in increased early embryo loss with increased growth in surviving fetuses.