Browsing by Subject "Resveratrol"

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Antioxidants Attenuate Heat Shock Induced Premature Senescence of Bovine Mesenchymal Stem Cells
(2022) Nir, Dana; Ribarski-Chorev, Ivana; Shimoni, Chen; Strauss, Carmit; Frank, Jan; Schlesinger, Sharon
Mesenchymal stem cells (MSC) have many roles that are important for the body’s proper functioning. When the MSC pool is damaged, it is often correlated with impaired development or health of the organism. MSC are known for their anti-inflammatory, immunomodulatory and trophic characteristics that play an important role in the physiological homeostasis of many tissues. Heat shock impairs MSC capacity by inducing the generation of reactive oxygen species and mitochondrial dysfunction, which, in turn, send the cells into a state of premature senescence. Here, we pre-exposed MSC to melatonin, resveratrol, or curcumin, which are natural antioxidative compounds, and tested the protective effects of these substances from oxidative stress and aging. Our data showed that pre-exposure of MSC to antioxidants decreased reactive oxygen species while mitochondrial damage remained high. Additionally, although the proliferation of the cells was slow, antioxidants protected the cells from premature senescence, and subsequent cytokine release was prevented. We conclude that while elevated temperatures directly cause mitochondrial damage, senescence is induced by elevated ROS levels. We suggest that heat shock alters cell and tissue homeostasis by several independent mechanisms; however, reducing tissue senescence will reduce damage and provide a pathway to overcome physiological challenges in animals.
Immunomodulatory effects of resveratrol on human intestinal mast cell signaling in vitro and mast cell associated enteritis and colitis in mice
(2023) Bilotta, Sabrina; Lorentz, Axel
By releasing their pre-stored or de novo synthesized mediators, mast cells (MC) are important immunoregulatory cells responsible for a variety of inflammatory reactions. Although known to be major effector cells in immunoglobuline (Ig) E dependent allergic reactions, MC have been widely shown to play a role in various inflammations of the gut. Diseases of the gastrointestinal tract (GIT) are widespread and multicausal. Those affected suffer from the sometimes severe symptoms and may experience restrictions on their daily life. Even if conventional medication is applied routinely, aim of the past and current research is to establish supportive and/or alternative medication that is based on natural substances. These may be on the basis of small natural components like resveratrol, a stilbene mostly found in grapes. Numerous positive properties are attributed to resveratrol. These are anti-inflammatory, anti-cancerogenic, anti-oxidative, as well as neuroprotective effects. The use of substances of natural origin as so-called nutraceuticals can help to increase the acceptance of medication by those affected, but also to reduce and overcome the side effects associated with conventional treatment. Effects of resveratrol were examined on the reactivity of MC isolated from patients’ tissue undergoing bowel resection. The results of this work show that resveratrol exhibited potent inhibitory effects on high affinity IgE receptor mediated activation of MC, strongly inhibiting not only MC degranulation, but also gene expression of the pro-inflammatory cytokines C-X-C motif chemokine ligand (CXCL) 8, C-C motif chemokine ligand (CCL) 2, CCL3, CCL4 and tumor necrosis factor (TNF-) α. Ultimately, the intracellular signaling cascade triggered during MC activation via IgE receptor leads to mediator release. Following IgE receptor mediated activation, phosphorylation of signaling molecules like extracellular signal-regulated kinase (ERK) 1/2 and signal transducer and activator of transcription (STAT) 3, occurs. ERK1/2 was found to be responsible for phosphorylation of mitochondrial STAT3, which contributes significantly to MC degranulation. Treatment with resveratrol was able to inhibit the phosphorylation of STAT3 by more than 50 % and that of ERK1/2 by almost 100 %. Furthermore, the experiments performed succeeded in isolating the mitochondrial fraction from relatively low human intestinal MC (hiMC) numbers. Also, in this fraction we could detect phosphorylation of STAT3 and ERK1/2 after MC activation, which was reduced after treatment with resveratrol. Having shown the strong inhibitory effects in vitro, we set out to examine immunomodulatory effects of resveratrol in vivo. Presence and activity of MC are closely related to intestinal inflammations in consequence of food allergy (FA) and inflammatory bowel disease (IBD). In mice, FA can be studied using the ovalbumin (OVA)-induced allergic enteritis model and colitis can be studied using the IL-10 knockout (-/-) mice, which develop a spontaneous form of chronic colitis. We could show that the oral application of resveratrol inhibited the increase of MC numbers in the colon and duodenum of affected animals in both experimental settings. Less pronounced but still visible effects of resveratrol administration were observed in the colon with regard to epithelial damage, cell infiltration and reduction of goblet cell numbers. In all cases, based on a scoring system, the damage decreased to the level of the corresponding controls receiving no additive and in which no allergic enteritis was induced or nor colitis developed. Overall, allergic enteritis resulted in a weaker symptomatology, and IL-10-/- animals showed a delayed appearance of the typical symptoms. The results of this thesis show a strong inhibitory effect of resveratrol on hiMC. This could be detected for mediator release as well as on gene expression levels and in the phosphorylation of the signaling molecules ERK1/2 and STAT3, which we could also identify in the mitochondria of hiMC. We observed positive influences on MC-associated parameters in the OVA enteritis and IL-10-/- colitis mouse models. With regard to its use as nutraceutical, resveratrol could therefore come more of a focus in the future.
Resistenz von Hopfen, Humulus lupulus L., gegen die Hopfenblattlaus, Phorodon humuli (Schrank)
(2010) Kryvynets, Oleg; Zebitz, Claus P. W.
Non-chemical methods controlling the damson-hop aphid, Phorodon humuli (Schrank) have recently gained importance, due to its great economical relevance and increasing problems with its chemical control. Breeding for the classic 'Genetically controlled resistance', where the plant exerts negative influence on the pest's behaviour during feeding, in this case appears as the only promising method because so far no other efficient biological control methods are available. In order to analyse the host-parasite relationship between hop and damson-hop aphid, and to provide a reliable, standardised screening method based on line-specific host selection behaviour, 1. the composition of the aphid's food, 2. hardness of hop tissue, 3. host selection behaviour and 4. parameters of aphid growth and development were investigated. In the apoplast (Intercellular washing fluid) of leaves and cones from all hop lines resveratrol was found, which also indicates an accumulation of its glycosidic form in the plant tissue. In contrast, no resveratrol could be found in samples of non-transgenic hop. An analysis for bitter acids detected alpha- and beta-acids in the cones only, not however in the intercellular space of the leaves. In a comparative study of plant tissues the contents of lupulones in leaf extracts from transgenic plants (except Tk160 and Tk424) was lower, the contents of humulones higher compared with those from non-transgenic plants. Generally leaf extracts showed higher contents of alpha- than of beta-acids. Resveratrol was not found in any of the leaf- or cone-extracts. Tissue hardness differed between transgenic and non-transgenic plants as well as between those from the glasshouse and from open land. In the field-grown plants it was definitely higher. Leaves of transgenic lines were harder than those of non-transgenic ones. This difference was pronounced particularly in young leaves. Significant differences were observed among parameters of aphid growth and development. The individual transgenic lines exert significantly different influence on P. humuli in respect of relative growth rate of individuals, rate of population increase and fecundity. There was no significant difference between the variants regarding the parameters rDS-value, life span and number of embryos. Host selection behaviour was different on transgenic versus non-transgenic plants. On leaves of transgenic plants a slowing down of food intake from the phloem and an extension of water intake from the xylem were observed. On the cones no similar effect ? general reduction or extension of intake from phloem or xylem in comparison to non-transgenic plants ? could be ascertained. Generally a strong decrease in food intake from the phloem of cones compared to that of the leaves was observed, caused by frequent phases of aphid inactivity on cones. Aphid behaviour on artificial diets was definitely influenced by different concentrations of bitter acids and resveratrol. A gradual increase in bitter acid concentration first prolonged or raised some EPG-parameters and then shortened or reduced them subsequently. This means that the aphids first reacted negatively, from a certain concentration of bitter acids on, however, positively to these substances. A raise in resveratrol concentrations led in the whole course either to a notable increase or decrease of values for the individual EPG-parameters. This suggests a xenobiotic resistance effected by this substance. Correlations between the experimental data showed the following dependencies: The humulones and lupulones found in intercellular washing fluid and in tissue extracts influence EPG-parameters that indicate factors located in the mesophyll. The duration of those phases of the penetration that take place in the intercellular space is reduced with increasing concentrations of humulones and lupulones. Food quality and quantity in plants from the glasshouse had no negative effects on the damson-hop aphid. On field-grown plants different effects of alpha- and beta-acids in the extracts on the aphids were ascertained. The contents of lupulones in cone- and leaf-extracts exerted a more inhibiting, the humulones a more promotional effect on the aphids during feeding. As with the overall contents of humulone and lupulone a different influence of individual bitter acids on aphid behaviour was recognisable in EPG-parameters. On cones the strong behaviour modification by the examined substances took effect on the mesophyll level and in the phloem. Positive correlations between the adult weight of the aphids as well as the amount of offspring per life span per insect and the bitter acid contents indicate an influence in favour of the insect. Negative correlations between the rm -value and the bitter acid contents, however, show an influence on the aphids in favour of the plant. Higher bitter acid concentrations reduce the development rate of aphid populations. Notable differences between transgenic and non-transgenic plants as well as varying effects of examined substances on the aphids, partly favourable for the plant, partly favourable for the pest, were found. These differences were partially clarified by comparing the effects of the substances when administered with artificial diets. The exact mode of action of resveratrol and its derivatives in transgenic hop lines on the damson-hop aphid requires further examination. A direct toxic effect on the aphids is very probable. As a conclusion from the clustering by examined parameters the transgenic hop line Tk424 can be designated as optimal.