Podophyllotoxin and rutin in combination prevents oxidative stress mediated cell death and advances revival of mice gastrointestine following lethal radiation injury

Intestinal injury is inevitable during exposure to high radiation doses and is a common side effect observed during abdominal/pelvic radiotherapy. Yet, no radiation countermeasures are available for gastrointestine (GI) injury management. The aim of this study is to determine the effects of podophyllotoxin and rutin in combination (G-003M) on ionising radiation induced GI injury. We prophylactically administered G-003M to C57BL/6J mice exposed to 9?Gy total body radiation (TBI) and assessed for morphological changes, loss in absorption, fluid retention, biochemical alterations, immunohistochemical analysis to study cPARP, caspase-3, PCNA expression, and TUNEL staining. The irradiated intestine demonstrated extensive loss in crypts and villi, disrupted mucosal lining with reduced xylose uptake and enhanced fluid level post 7-day radiation. Mice receiving G-003M before radiation showed significant protection to intestinal epithelium, better allocation of secretory goblet cells, recovery in absorption, and reduced intestinal oedema. Additionally, G-003M administration also prevented radiation induced ROS generation, lipid peroxidation (MDA levels) and maintained the intestinal glutathione pool compared to the irradiated animals. G-003M supplementation also resulted in restoration of intestinal mitochondrial membrane potential, which was otherwise depolarised by radiation treatment. Immunohistochemical analysis demonstrated decrease in c-PARP and caspase-3 expression in jejuna cross sections and upregulation of PCNA in G-003M treated crypt cells as compared to 9?Gy irradiated mice. Our findings show that G-003M augment survival of mice against lethal radiation by promoting structural and functional regeneration in intestinal tissue. This combination therefore can be effectively explored for preventing radiation induced GI toxicity.     

Flavone O- and C-glycosides of Rhynchosia beddomei

A new flavone-O-glycoside isolated front the leaves of Rhynchosia beddomei has been characterized as 3′,4′-di-O-methylluteolin-7-O-glucuronide.     

Tirumalin,a new prenylated dihydroflavonol from Rhynchosia cyanosperma

A new dihydroflavonol has been isolated together with the known flavonol-O- glycosides, rutin and kaempferol-3-rutinoside, and (+)-pinitol from the leaves of R. cyanosperma Benth. The dihydroflavonol was identified as (+)-(2R, 3R)-8-C-prenyltaxifolin-7, 4′-dimethyl ether on the basis of spectroscopic studies and the compound given the trivial name tirumalin.     

Influence of secondary compounds in the phloem sap of cassava on expression of antibiosis towards the mealybugPhenacoccus manihoti

Identification and assay of cyanogenic and phenolic compounds in phloem sap of cassava (Manihot esculenta Crantz, Euphorbiaceae) and in honeydew of the cassava mealybugPhenacoccus manihoti Matt. Ferr. (Homoptera, Pseudococcidae) were realised. Cyanogenic glucosides and three flavonoid glycosides (rutin, kaempferol glycoside-1 and kaempferol glycoside-2) were found to be translocated in cassava phloem sap and consumed by the mealygug. Differences in profiles of secondary compounds of phloem sap and honeydew samples, characterised mainly by the appearance of free cyanide and of a free flavonoid, suggest the metabolic processing of at least some of the ingested compounds. The relationship between foliar concentrations of these different compounds and expression of the antibiotic resistance of cassava towardsP. manihoti was also investigated in 7 varieties of cassava and in the ‘faux-caoutchouc’ hybrid. Infestation by mealybug was followed by a clear increase in levels of both rutin and kaempferol glycoside-2, while no modification in cyanide contents was noted. The best rank correlation between antibiotic resistance (measured by the intrinsic rate of increase r _c ) and secondary compounds analyzed is observed with rutin contents of infested plants (ρ=−0.73; p=0.05). The possible implication of this compound in the biochemical mechanisms accompanying cassava defence reaction to mealybug attack is discussed.

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Résumé Ce travail présente l'identification et le dosage des substances secondaires (composés cyanés et phénoliques) présentes dans la sève phloémienne du manioc (Manihot esculenta Crantz, Euphabiaceae) et dans le miellat de la cochenille farineusePhenacoccus manihoti Matt. Ferr. (Homoptera, Pseudococcidae). Des glycosides cyanogéniques et trois flavono?des glycosylés majeurs (rutine, kaempferol glycoside-1 et kaempferol glycoside-2) sont transportés par la sève phloémienne du manioc et consommés par la cochenille. Le profil sensiblement différent des composés secondaires du meillat de la cochenille, en particulier l'apparition d'un flavonoide libre et de cyanure, suggère une modification de certains composés lors du transit intestinal. La relation entre les teneurs de ces différentes substances dans le liquide foliaire de 7 variétés de manioc et du ‘faux-caoutchouc’ (hybride deM. esculenta et deM. glaziovii) et l'expression de leur résistance antibiotique vis-à-vis deP. manihoti a également été étudiée. L'infestation par la cochenille se traduit par une importante augmentation des teneurs en rutine et en kaempferol glycoside-2, alors qu'aucune modification des teneurs en cyanure libre n'est enregistrée. La meilleure corrélation entre la résistance par antibiose, exprimée par la capacité intrinsèque d'accroissement r _c , et les teneurs en substances secondaires analysées est observée avec les teneurs en rutine des plants infestés (ρ=−0.73; p=0.05). L'association éventuelle de ce glycoside aux mécanismes biochimiques de défense du manioc à la cochenille farineuse est discutée.

     

Rutin: a phagostimulant for the polyphagous acridid Schistocerca americana

Rutin was demonstrated to be a phagostimulant for the grasshopper Schistocerca americana across a very wide concentration range. The effect was not maintained over a period of days if the insects had already ingested a large amount, but when individuals were given different concentrations on disks as supplements to their lettuce diet, they tended to self select a moderate quantity on a daily basis. In long term experiments on food utilization and growth rates using artificial diet, no beneficial effects of rutin could be demonstrated. Ingested rutin was absorbed and some of it deposited in the cuticle. Most was excreted as the aglycone quercetin. The possible functional significance of the phagostimulatory effect is discussed.Dedicated to G.B. Marini-Bettolo     

Quantification of Phenolic Component by LC-HESI-MS/MS and Evaluation of Antioxidant Activities of Crocus Ancyrensis (Ankara Çiğdemi) Extracts Obtained with Different Solvents

In this study, Crocus ancyrensis was extracted from different parts of the plants with various solvents and their antioxidant activities and phenolic contents were investigated in detail for the first time. The highest amount of total phenolic substance in all parts of the plant was determined in the stigmaless flower. In the DPPH and FRAP methods, the highest antioxidant activity was obtained from the water extraction from the plant. Rutin is the highest detected by LC MS/MS. Stigmaless flower extract in all solvents is attributed to the component that contributes the most to antioxidant capacity. p-hydroxy benzoic acid was detected as the highest phenolic component after rutin. When the antioxidant activity results were examined, it was determined that the highest activity was in the water extract. As a result, it is evaluated that rutin and p-hydroxybenzoic acid in the plant contribute to the antioxidant capacity.     

A xanthone glycoside from Tripterospermum taiwanense and rutin from Gentiana flavo-maculata

Oleanolic acid, norathyriol, and a new xanthone glycoside, tripteroside, which was characterized as norathyriol 6-O-β-d-glucoside, were isolated from the fresh herb Tripterospermum taiwanense, and quercetin and rutin were isolated from the fresh herb Gentiana flavo-maculata.