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.

RIFM fragrance ingredient safety assessment, 3,7-dimethyl-1,6-nonadien-3-ol, CAS Registry Number 10339-55-6.

The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the suitable read across analog linalool (CAS # 78-70-6) show that this material is not genotoxic nor does it have skin sensitization potential and also provided a MOE > 100 for the local respiratory endpoint. The repeated dose, developmental and reproductive toxicity endpoints were completed using nerolidol (isomer unspecified, CAS # 7212-44-4) as a suitable read across analog, which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework.

RIFM fragrance ingredient safety assessment, 2-methylundecanol, CAS Registry Number 10522-26-6.

This material was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the suitable read across analogs 2-butyloctan-1-ol (CAS # 3913-02-8) and 2-ethyl-1-hexanol (CAS # 104-76-7) show that this material is not genotoxic nor does it have skin sensitization potential. The reproductive and local respiratory toxicity endpoints were completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (0.03 and 1.4 mg/day, respectively). The repeated dose toxicity endpoint was completed using 2-ethyl-1-hexanol (CAS # 104-76-7) and 1-heptanol, 2-propyl (CAS # 10042-59-8) as suitable read across analogs, which provided a MOE > 100. The developmental toxicity endpoint was completed using 2-ethyl-1-hexanol (CAS # 104-76-7) as a suitable read across analog, which provided a MOE > 100 The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework.

Acute and chronic oral toxicity of a partially purified plaunotol extract from Croton stellatopilosus Ohba.

Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves of Croton stellatopilosus Ohba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluated in vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD50 = 10.25 g/kg). The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11-1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550-1,100 mg/kg/day). These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans.

6-gingerdiols as the major metabolites of 6-gingerol in cancer cells and in mice and their cytotoxic effects on human cancer cells.

6-Gingerol, a major pungent component of ginger (Zingiber officinale Roscoe, Zingiberaceae), has been reported to have antitumor activities. However, the metabolic fate of 6-gingerol and the contribution of its metabolites to the observed activities are still unclear. In the present study, we investigated the biotransformation of 6-gingerol in different cancer cells and in mice, purified and identified the major metabolites from human lung cancer cells, and determined the effects of the major metabolites on the proliferation of human cancer cells. Our results show that 6-gingerol is extensively metabolized in H-1299 human lung cancer cells, CL-13 mouse lung cancer cells, HCT-116 and HT-29 human colon cancer cells, and in mice. The two major metabolites in H-1299 cells were purified and identified as (3R,5S)-6-gingerdiol (M1) and (3S,5S)-6-gingerdiol (M2) based on the analysis of their 1D and 2D NMR data. Both metabolites induced cytotoxicity in cancer cells after 24 h, with M1 having a comparable effect to 6-gingerol in H-1299 cells.

Isolation of borrelidin as a phytotoxic compound from a potato pathogenic streptomyces strain.

Streptomyces species strain GK18, isolated in Iran, induced deep-pitted lesions on potato tubers, lesions different from the raised lesions induced by the usual scab-causing phytotoxin, thaxtomin. In addition, neither thaxtomin production nor hybridization to its biosynthetic probe was detected for strain GK18, suggesting the production of a different phytotoxin. The active component was extracted with ethyl acetate from culture filtrate of strain GK18, purified by gel filtration and silica gel chromatography, and identified as an 18-membered macrolide, borrelidin, by spectroscopic analysis. The purified borrelidin induced necrosis on potato tuber slices and inhibited the growth of shoots and roots of radish seedlings. This is the first report on the phytotoxicity of borrelidin as a possible causative compound of potato scab disease.

A new adjacent bis-tetrahydrofuran annonaceous acetogenin from the seeds of Uvaria chamae.

A novel acetogenin, joolanin ( 1), along with eight known acetogenins, squamocin ( 2), desacetyluvaricin ( 3), chamuvarinin ( 4), tripoxyrollin ( 5), diepoxyrollin ( 6), dieporeticanin-1 ( 7), dieporeticanin-2 ( 8) and dieporeticenin ( 9) were isolated from the seeds of Uvaria chamae (Annonaceae). Compound 1, the first adjacent bis-tetrahydrofuranic ring acetogenin bearing a ketone group at C-5, shows significant cytotoxicity towards the KB 3 - 1 cell line (IC (50) = 0.4 nM).

Botanical insecticides, deterrents, and repellents in modern agriculture and an increasingly regulated world.

Botanical insecticides have long been touted as attractive alternatives to synthetic chemical insecticides for pest management because botanicals reputedly pose little threat to the environment or to human health. The body of scientific literature documenting bioactivity of plant derivatives to arthropod pests continues to expand, yet only a handful of botanicals are currently used in agriculture in the industrialized world, and there are few prospects for commercial development of new botanical products. Pyrethrum and neem are well established commercially, pesticides based on plant essential oils have recently entered the marketplace, and the use of rotenone appears to be waning. A number of plant substances have been considered for use as insect antifeedants or repellents, but apart from some natural mosquito repellents, little commercial success has ensued for plant substances that modify arthropod behavior. Several factors appear to limit the success of botanicals, most notably regulatory barriers and the availability of competing products (newer synthetics, fermentation products, microbials) that are cost-effective and relatively safe compared with their predecessors. In the context of agricultural pest management, botanical insecticides are best suited for use in organic food production in industrialized countries but can play a much greater role in the production and postharvest protection of food in developing countries.

Differential cytotoxic effects of Annona squamosa seed extracts on human tumour cell lines: role of reactive oxygen species and glutathione.

Annonaceous acetogenins are a new class of compounds that have been reported to have potent pesticidal, parasiticidal, anti-microbial, cell growth inhibitory activities. In this study, organic and aqueous extracts from the defatted seeds of Annona squamosa (custard apple) were tested on different human tumour cell lines for antitumoural activity. While organic and aqueous extracts induced apoptosis in MCF-7 and K-562 cells, they failed to do so in COLO-205 cells. Treatment of MCF-7 and K-562 cells with organic and aqueous extracts resulted in nuclear condensation, DNA fragmentation, induction of reactive oxygen species (ROS) generation and reduced intracellular glutathione levels. In addition downregulation of Bcl-2 and PS externalization by Annexin-V staining suggested induction of apoptosis in MCF-7 and K-562 cells by both the extracts through oxidative stress. On the contrary, COLO-205 cells showed only PS externalization but no change in ROS and glutathione levels. These observations suggest that the induction of apoptosis by A. squamosa extracts can be selective for certain types of cancerous cells.

Molluscicidal and antifungal activity of Erigeron speciosus steam distillate.

The steam-distilled fraction of the aerial parts of Erigeron speciosus (Lindl) DC was tested for activity against strawberry plant pathogenic fungi Botrytis cinerea Pers ex Fr, Colletotrichum acutatum Simmonds, C fragariae Brooks, C gloeosporioides (Penz) Penz & Sacc, and the intermediate host snail Planobdella trivolvis that harbors the trematode, Bolbophorus confusus, that infests and causes severe infections in pond-raised catfish in the Mississippi Delta region of the USA. Bioautography on silica TLC plates demonstrated antifungal activity in the steam distillate. Preliminary bioassays of the steam distillate indicated the presence of phytochemicals toxic to P trivolvis. The bioactive compounds methyl 2Z, 8Z-deca-2,8-diene-4,6-diynoate and its 2E, 8E isomer were isolated by bioassay-guided fractionation and chromatographic techniques and identified by 1H NMR spectroscopy.

Strategies for reducing solvent toxicity in extractive ethanol fermentation.

Extractive fermentation is a widely preferred technique in which the products of fermentation are removed from the fermentation medium by a proper solvent, in order to avoid the inhibitory effects of the products. In this work, decanol, which has a high distribution coefficient with respect to the biocompatible solvents, was used in extractive ethanol fermentation. In order to reduce decanol toxicity, Saccharomyces cerevisiae cells were immobilized in calcium alginate gel. Further, sunflower oil and Al2O3 were added to the immobilization media. Experiments were performed in 250-mL Erlenmeyer flasks that were placed in the constant-temperature bath of a constant stirring-rate shaker. Ethanol concentrations were measured to observe the effect of various parameters on ethanol production. Immobilization media included 10, 20, and 30% sunflower oil, or 5, 10, and 20% Al2O3, or Al2O3 and sunflower oil together. The ratio of the volume of aqueous phase to that of decanol phase ranged from 2:1 to 6:1. It was observed that protection depends on the oil, Al2O3, and decanol amounts. Utilization of sunflower oil (30%) and Al2O3 (5%) together yielded best results.

Kneglomeratanol, kneglomeratanones A and B, and related bioactive compounds from Knema glomerata.

One new phenylalkyl phenol, kneglomeratanol [1], and two new acetophenones, kneglomeratanones A [2] and B [3], together with ten known compounds, 3-(12'-phenyldodecyl)-phenol [4], 3-(10'-phenyldecyl)-phenol [5], 5-pentadecylresorcinol [6], 5-(10'-phenyldecyl)-resorcinol [7], 5-(12'-phenyldodecyl)-resorcinol [8], 2,4-dihydroxy-6-(10'-phenyldecyl)-acetophenone [9], 2-hydroxy-6-(12'-phenyldodecyl)-benzoic acid [10], formononetin, biochanin A, and 8-O-methylretusin, have been isolated from the stem bark of Knema glomerata. Brine shrimp lethality was used for the activity-directed chromatographic fractionations. All of these compounds showed moderate but significant toxicities to three human tumor cell lines and inhibited the growth of crown gall tumors on discs of potato tubers.

Bioactive metabolites from Sicilian marine fennel, Crithmum maritimum.

Bioactivity-guided fractionation of the lipid extract of Crithmum maritimum using the brine shrimp lethality assay led to the isolation of three bioactive compounds. Two of these are known C17 polyacetylenic metabolites, falcarinol [1] and falcarindiol [2], previously isolated from several species of the Umbelliferae and Araliaceae. The third active principle was identified as O-geranylvanillin [3], an aromatic ether described in the literature as a synthetic compound but unknown as a natural product. Cytotoxic activity of the pure compounds was significant for 1 and 2, much less intense for 3.

Preclinical toxicology studies with the lipid-regulating agent gemcadiol.

Gemcadiol is a medium-length diol moiety with lipid-regulating properties in animals and man. The compound was not toxic when single doses were administered to rodents with the lethal dose greater than 7000 mg/kg in rats and mice. Rats treated for 13 or 52 weeks with 30 to 300 mg/kg had reversible food intake suppression and weight gain inhibition, decreased blood cholesterol, slight anemia, and generally dose-related but reversible decreases in glucose, and increases in alkaline phosphatase and blood urea nitrogen. Liver weights were increased, and there was accompanying hypertrophy and increased cytoplasmic eosinophilia of hepatocytes with associated peroxisome proliferation. Rats treated for 52 weeks also had mild renal tubular dilatation. Dogs given 25 to 300 mg/kg of gemcadiol for up to 52 weeks tolerated the compound better than rats. Effects related to compound administration were elevated serum alanine aminotransferase activity in female animals only, and microscopic cytoplasmic vacuolation and hyaline body formation in both sexes. Monkeys given 25 to 300 mg/kg gemcadiol for 13 weeks had slightly decreased serum cholesterol and slightly increased serum creatine phosphokinase. Teratology studies in rats or rabbits indicated no teratogenic response. Gemcadiol affects principally the liver, and the hepatic alterations seen in rats and dogs may reflect compensatory manifestations of altered metabolism related to the lipid-regulating activity of the compound.

Pharmacological studies on ginger. I. Pharmacological actions of pungent constitutents, (6)-gingerol and (6)-shogaol.

General pharmacological studies were performed on (6)-gingerol and (6)-shogaol which are the pungent constituents of ginger (Zingiber officinale Roscoe). Intravenous (i.v.) administration of (6)-gingerol (at 1.75-3.5 mg/kg) or (6)-shogaol (at 1.75-3.5 mg/kg) and oral administration of them (at 70-140 mg/kg) produced an inhibition of spontaneous motor activity, an antipyretic and analgesic effects, prolonged hexobarbital-induced sleeping time, and these effects of (6)-shogaol were mostly more intensive than that of (6)-gingerol. (6)-Shogaol showed an intense antitussive effect in comparison with dihydrocodeine phosphate. In the electro-encephalogram of cortex, the low amplitude fast wave pattern was observed for 5 min after i.v. administration of (6)-shogaol, and then changed to the drowsy pattern, which was restored after 60 min. In the gastro-intestinal system, (6)-shogaol intensively inhibited the traverse of charcoal meal through the intestine in contrast with (6)-gingerol after i.v. administration of 3.5 mg/kg, but (6)-shogaol facilitated such an intestinal function after oral administration of 35 mg/kg. Both (6)-shogaol and (6)-gingerol suppressed gastric contraction in situ, and the suppression by the former was more intensive than that by the latter. In the cardiovascular system, both (6)-shogaol and (6)-gingerol produced depressor response at lower doses on the blood pressure. At high doses, both drugs produced three phase pattern.