Does rosmarinic acid treatment have protective role against sepsis-induced oxidative damage in Wistar Albino rats?

Reactive oxygen species are believed to be involved in the development of sepsis. Plant-derived phenolic compounds are thought to be possible therapeutic agents against sepsis because of their antioxidant properties. Rosmarinic acid (RA) is a phenolic compound commonly found in various plants, which has many biological activities including antioxidant activity. The aim of this study was to investigate the effects of RA on sepsis-induced DNA damage in the lymphocytes and liver and kidney cells of Wistar albino rats by alkaline comet assay with and without formamidopyrimidine DNA glycosylase protein. The oxidative stress parameters such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and total glutathione (GSH) and malondialdehyde (MDA) levels in the liver and kidney tissues and an inflammatory cytokine, tumor necrosis factor α (TNF-α) level in plasma were also evaluated. It is found that DNA damage in the lymphocytes, livers, and kidneys of the RA-treated rats was significantly lower than that in the sepsis-induced rats. RA treatment also decreased the MDA levels and increased the GSH levels and SOD and GSH-Px activities in the livers and kidneys of the sepsis-induced rats. Plasma TNF-α level was found to be decreased in the RA-treated rats. It seems that RA might have a role in the attenuation of sepsis-induced oxidative damage not only by decreasing the DNA damage but also by increasing the antioxidant status and DNA repair capacity of the animals.

Protective effects of resveratrol on sepsis-induced DNA damage in the lymphocytes of rats.

Sepsis, often initiated by an infection, is a state of disrupted inflammatory homeostasis. There is increasing evidence that oxidative stress has an important role in the development of sepsis-induced multiorgan failure. Resveratrol (RV) is a polyphenolic compound found in the skin of red fruits, such as mulberries and red grapes, and in peanuts. RV has been reported to have an antioxidant, antiproliferative, and anti-inflammatory properties in various models. It has also been found to inhibit the proliferation of a variety of human cancer cell lines, including breast, prostate, colon, pancreatic, and thyroid. This study has been undertaken to assess the role of RV on the sepsis-induced oxidative DNA damage in the lymphocytes of Wistar albino rats by the standard and formamidopyrimidine DNA glycosylase (Fpg)-modified comet assays. The parameters of tail length, tail intensity, and tail moment were evaluated for the determination of DNA damage. According to the study, the DNA damage was found to be significantly higher in the sepsis-induced rats when compared with the control rats (p < 0.05). The parameters were significantly decreased in the RV-treated sepsis-induced group when compared with the sepsis-induced group. The parameters in the sepsis-induced rats were found to be significantly higher in the Fpg-modified comet assay when compared with the standard comet assay (p < 0.05), and RV treatment decreases the DNA damage in the sepsis-induced rats, suggesting that the oxidative stress is likely to be responsible for DNA damage and RV might have a role in the prevention of sepsis-induced oxidative DNA damage.

Modulating effects of flavonoids on food mutagens in human blood and sperm samples in the comet assay.

The flavonoids silymarin, myricetin, quercetin, kaempferol, rutin, and kaempferol-3-rutinoside have been examined in combination with the food mutagens 3-amino-1-methyl-5H-pyrido (4,3-b)indole (Trp) and 2-amino-3-methylimidazo-4,5-f)quinoline (IQ) in the Comet assay in human lymphocytes from donors A and B and human sperm from donor B. These compounds alone have been shown to produce positive responses in the Comet assay, as have the food mutagens. However, in combination with the food mutagens, the flavonoids produced antigenotoxic effects since DNA damage was reduced in the Comet assay in human lymphocytes and sperm over a similar dose range in the absence of metabolic activation. Only quercetin and kaempferol were examined in blood with metabolic activation, but there was no difference in response to that obtained without activation. In the blood there was an exacerbation or synergy of response at the lowest doses of the flavonoids. In the sperm this was also the case with silymarin and myricetin. With kaempferol there was no antigenotoxic effect and quercetin protected below baseline levels. Since the effects were observed in lymphocytes and sperm over a similar dose range, it would suggest that the Comet assay responses occur in somatic and germ cells in a one-to-one ratio. These results have implications for man in terms of risk assessment and in the modulation of isolated food constituents.

An investigation of some Turkish herbal medicines in Salmonella typhimurium and in the COMET assay in human lymphocytes.

Medicinal plants play a major role in the life of Turkish people and of late medicinal plant usage has increased in many countries. Green plants in general contain mutagenic and carcinogenic substances, but there is little information about the biological activities of herbal medicine. In the present study, therefore, various Turkish medicinal herbs were investigated for their genotoxic potential in the Salmonella typhimurium microsomal activation assay and the alkaline single cell gel electrophoresis (COMET) assay. Extracts from these medicinal herbs and some fractions of these extracts were examined. The species investigated were Arctium minus, Ecballium elatterium, Momordica charantia, Plantago major, Urtica dioica, Viscum album, Salvia triloba, Euphorbia rigida, Stachys lavandulifolia, Acteoside, Abies nordmannia. They are used for various immune disorders and are applied either topically or taken orally as a herbal tea. Of the 19 samples of the extracts and fractions investigated, none produced a positive response in strains TA98 and TA100 with or without metabolic activation, but all produced an increase above negative control values in the COMET assay. Some extracts were investigated further and produced dose-related increases. In the case of Urtica and Euphorbia species, where two fractions from these plants were examined, one fraction produced a greater response than the other. It is suggested that the lesser response of the fractions might be due to less DNA strand-breaking agents in the fractions or they may have antigenotoxic properties. The breaks that are detected in the COMET assay could be alkali-labile AP-sites and intermediates in base- or nucleotide-excision repair and are difficult to interpret in terms of hazard for man. Further studies with additional genotoxicity assays would be required to make such a prediction.

Karsoside and scropolioside D, two new iridoid glycosides from Scrophularia ilwensis.

Two new iridoid glycosides, karsoside [1] and scropolioside D [2], were isolated from the aerial parts of Scrophularia ilwensis. Their structures were elucidated on the basis of chemical and spectral data as 6'-O-(beta-D-xylopyranosyl)-methylcatalpol and 6-O-[(2",4"-di-O-acetyl-3"-O-trans-cinnamoyl)-alpha-L-rhamnopyranosyl]- catalpol, respectively. Additionally, four known iridoids (aucubin, harpagide, 8-O-acetylharpagide, and ajugol), a phenylpropanoid glycoside (angoroside C), and two flavonoids (quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside) were isolated and identified.

Two phenethyl alcohol glycosides from Scutellaria orientalis subsp. pinnatifida.

Two new phenethyl alcohol glycosides, darendoside A and B (= deacyl martynoside) were isolated from the methanolic extract of the aerial parts of Scutellaria orientalis subsp. pinnatifida, along with four known glycosides, syringin, martynoside, leucosceptoside A and verbascoside. On the basis of chemical and spectral evidence the structures of darendoside A and B were determined as beta-(4-hydroxyphenyl)ethyl O-beta-D-apiofuranosyl-(1-->2)-O-beta-D-glucopyranoside and beta-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-rhamnopyranosyl-(1-->3)-O-beta-D-glucopyranoside (= deacyl martynoside), respectively.

Phlinosides D and E, phenylpropanoid glycosides, and iridoids from Phlomis linearis.

Two new phenylpropanoid glycosides, phlinosides D and E were isolated from the methanolic extract of the aerial parts of Phlomis linearis, along with the known iridoid glucosides, lamiide, ipolamiide and auroside (= 5-hydroxy-8-epiloganin). On the basis of chemical and spectral evidence the structures of phlinosides D and E were determined as 3,4-dihydroxy-beta-phenylethoxy-O-beta-D-xylopyranosyl-(1----2)-al pha-L-rhamnopyranosyl-(1----3)-4-O-feruloyl-beta-D-glucopyranoside and 3,4-dihydroxy-beta-phenylethoxy-O-alpha-L-rhamnopyranosyl-(1----2) -alpha-L- rhamnopyranosyl-(1----3)-4-O-feruloyl-beta-D-glucopyranoside, respectively.

Phlinosides A, B and C, three phenylpropanoid glycosides from Phlomis linearis.

Three new phenylpropanoid glycosides, phlinosides A, B and C were isolated from a methanolic extract of the aerial parts of Phlomis linearis. On the basis of chemical and spectral evidence their structures were determined as 3,4-dihydroxy-beta-phenylethoxy-O-beta-D-glucopyranosyl-(1----2)-a lpha-L- rhamnopyranosyl-(1----3)-4-O-caffeoyl-beta-D-glucopyranoside, 3,4 dihydroxy-beta-phenylethoxy-O-beta-D-xylopyranosyl-(1----2)-alpha- L- rhamnopyranosyl-(1----3)-4-O-caffeoyl-beta-D-glucopyranoside and 3,4-dihydroxy-beta-phenylethoxy-O-alpha-L-rhamnopyranosyl-(1----2) -alpha- L-rhamnopyranosyl-(1----3)-4-O-caffeoyl-beta-D-glucopyranoside, respectively.