RESUMO
Most of the known senolytics are anti-cancer drugs or their derivative molecules. However, senolytics derived from the active ingredients of traditional Chinese medicine (TCM) are rarely reported. Here, we identified oridonin as a novel senolytic and further revealed that it might target a class of glutathione S-transferases to activate ROS-p38 signaling and induce apoptosis in senescent cells.
Assuntos
Apoptose , Senoterapia , Espécies Reativas de Oxigênio , Senescência Celular , Glutationa/farmacologia , Transferases/farmacologiaRESUMO
OBJECTIVES: Many plant-derived anti-aging preparations influence antioxidant defense system. Consumption of food supplemented with chili pepper powder was found to extend lifespan in the fruit fly, Drosophila melanogaster. The present study aimed to test a connection between life-extending effect of chili powder and antioxidant defense system of D. melanogaster. METHODS: Flies were reared for 15 days in the mortality cages on food with 0% (control), 0.04%, 0.12%, 0.4%, or 3% chili powder. Antioxidant and related enzymes, as well as oxidative stress indices were measured. RESULTS: Female flies that consumed chili-supplemented food had a 40-60% lower glutathione-S-transferase (GST) activity as compared with the control cohort. Activity of superoxide dismutase (SOD) was about 37% higher in males that consumed food with 3% chili powder in comparison with the control cohort. Many of the parameters studied were sex-dependent. CONCLUSIONS: Consumption of chili-supplemented food extends lifespan in fruit fly cohorts in a concentration- and gender-dependent manner. However, this extension is not mediated by a strengthening of antioxidant defenses. Consumption of chili-supplemented food does not change the specific relationship between antioxidant and related enzymes in D. melanogaster, and does not change the linkage of the activities of these enzymes to fly gender.
Assuntos
Antioxidantes , Drosophila melanogaster , Animais , Antioxidantes/metabolismo , Feminino , Alimentos Fortificados , Glutationa , Masculino , Estresse Oxidativo , Pós/farmacologia , Superóxido Dismutase/metabolismo , Transferases/farmacologiaRESUMO
BACKGROUND: In the wild various organisms contribute to daphnids diet. This study, intendeds to evaluate the potential of the concentration of Rhodopirellula rubra as a single or supplementary food source for Daphnia magna. METHODS: Feeding assays were performed according to standard guidelines for chronic assays (21 days), and life-history parameters and several biomarkers (protein content, oxidative stress, energetic reserves and pigments) were measured. Five food regimens were conducted with 20 individual replicates (A - R. subcapitata; 0.2 - suspension of R. rubra at 0.2 arbitrary units (AU); 0.4 - suspension of R. rubra at 0.4 AU; 0.2+A - suspension of R. rubra at 0.2+alga; 0.2+A-suspension of R. rubra at 0.4 AU + alga). Additionally, the effects of three diets (A, 0.2, and 0.2+A) on the longevity of D. magna were assessed. RESULTS: The five diets showed a different C, N, and carotenoids composition, with an increase in the mixed diets. The results confirmed that the mixed diets improved D. magna life-history parameters. A decrease in glycogen, and the increase of haemoglobin, protein, and gluthione-S-transferase (GST) were observed. Furthermore, D. magna fed with bacterial single diets, presented worsen life history parameters and a decrease in the protein content. An induction of oxidative stress response (increased catalase and GST), and a significant decrease in lipid peroxidation and an accumulation of glycogen and carotenoids were observed. Overall, an increase in the amount of R. rubra provided to D. magna, from 0.2 AU to 0.4 AU, negatively impacted daphnid performance. No significant effects on Daphnia longevity (a 110-day assay) were observed among the three diets tested. However, a significant survival percentage and fertility (cumulative offspring is more than twice) was observed when D. magna was fed with the mixed diet. CONCLUSIONS: Results demonstrated that different diets provided a nutritional diversified food to the daphnids that induced differences in D. magna performance. The mixed diets proved to be beneficial (with increase in offspring) on D. magna performance, independently of the bacterial concentration tested. When in single diet, bacterial concentration is not nutritionally sufficient to raise D. magna even when in increased concentration.
Assuntos
Daphnia , Poluentes Químicos da Água , Animais , Biomarcadores , Carotenoides/farmacologia , Catalase/farmacologia , Daphnia/fisiologia , Dieta , Glicogênio/farmacologia , Planctomycetales , Transferases/farmacologia , Poluentes Químicos da Água/farmacologiaRESUMO
Plants essentially require manganese (Mn) for their normal metabolic functioning. However, excess Mn in the cellular environment is detrimental to plant growth, development, and physio-biochemical functions. Taurine (TAU) is an amino acid with potent antioxidant and anti-inflammatory properties in animals and humans. However, no previous study has investigated the potential of TAU in plant metal stress tolerance. The current study provides some novel insights into the effect of TAU in modulating the defense system of Trifolium alexandrinum plants under Mn toxicity. Manganese toxicity resulted in higher oxidative stress and membrane damage through increased superoxide radical, hydrogen peroxide, malondialdehyde, and methylglyoxal generation alongside enhanced lipoxygenase (LOX) activity. Mn toxicity also resulted in limited uptake of potassium (K+), phosphorus (P), calcium (Ca2+), and increased the accumulation of Mn in both leaf and roots. However, TAU circumvented the Mn-induced oxidative stress by upregulating the activities of antioxidant enzymes (ascorbate peroxidase, peroxidase, catalase, glutathione reductase, glutathione-S-transferase, and superoxide dismutase) and levels of ascorbic acid, proline, anthocyanins, phenolics, flavonoids and glutathione (GSH). Taurine conspicuously improved the growth, photosynthetic pigments, hydrogen sulphide (H2S), and nitric oxide (NO) levels of Mn stressed plants. Taurine also improved the uptake of K+, Ca2+, P and reduced the Mn content in stressed plants. Overall, exogenous taurine might be a suitable strategy to combat Mn stress in T. alexandrinum plants but applications at field levels for various crops and metal toxicities and economic suitability need to be addressed before final recommendations.
Assuntos
Sulfeto de Hidrogênio , Trifolium , Aminoácidos/metabolismo , Antocianinas , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Ácido Ascórbico/farmacologia , Cálcio/metabolismo , Catalase/metabolismo , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/metabolismo , Lipoxigenases/metabolismo , Malondialdeído/metabolismo , Manganês/toxicidade , Óxido Nítrico/metabolismo , Nutrientes , Estresse Oxidativo , Fósforo/metabolismo , Fotossíntese , Potássio , Prolina/metabolismo , Aldeído Pirúvico/metabolismo , Aldeído Pirúvico/farmacologia , Superóxido Dismutase/metabolismo , Superóxidos , Taurina/farmacologia , Transferases/metabolismo , Transferases/farmacologia , Trifolium/metabolismoRESUMO
Green synthesis of nanoparticles using plant-based extracts is momentously used in different fields of science because of their environment-friendly nature and cost-effectiveness. In the present study, silver nanoparticles were synthesized by using rice husk (non-toxic agricultural by-product) to determine their efficacy against aphid's (Sitobion avanae) mortality and antioxidant enzymes. UV-VIS spectroscopy of synthesized nanoparticles showed the maximum absorption peak at 440 nm, FTIR exhibited different peaks, and SEM confirmed the roughly spherical shape and 70-80 nm size of silver nanoparticles. Aphids were reared on wheat seedlings in the laboratory at 20-25 °C and 16:8 (light:dark) photoperiod. Insecticidal bioassays were conducted on aphids at three different concentrations (200 ppm, 400 ppm, 600 ppm) of nanoparticles for 2 days. Results showed the highest mortality of aphids being 93.3% at 600 ppm nanoparticle concentration after 2 days while the lowest mortality was observed at 200 ppm. Furthermore, the effect of silver nanoparticles on antioxidant enzymes was studied. Results of enzyme assays revealed that enzyme activities of catalase and glutathione-s-transferase increased in response to increased nanoparticle concentration. The current findings suggested that silver nanoparticles have probation for replacing commercially available insecticides for combating pests.
Assuntos
Afídeos , Inseticidas , Nanopartículas Metálicas , Nanopartículas , Oryza , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Catalase , Glutationa/análise , Inseticidas/química , Inseticidas/farmacologia , Larva , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Prata/química , Prata/farmacologia , Transferases/análise , Transferases/farmacologiaRESUMO
The human (h) and mouse (m) prostacyclin receptors (IPs) undergo isoprenylation through attachment of a C-15 farnesyl moiety within their conserved carboxyl terminal -CSLC sequences. Herein, the effects of a novel farnesyl transferase inhibitor R115777 on signalling by the hIP and mIP, overexpressed in human embryonic kidney 293 cells, and by the hIP endogenously expressed in human erythroleukaemia cells were investigated. R115777 significantly impaired IP-mediated cyclic AMP generation (IC(50) 0.37-0.60 nm) and intracellular calcium ([Ca(2+)](i)) mobilization (IC(50) 37-65 nm), but had no effect on signalling by the control nonisoprenylated beta(2) adrenergic receptor or the alpha or beta isoforms of the human thromboxane A(2) receptor (TP). Additionally, R115777 significantly reduced IP-mediated cross-desensitization of signalling by the TP alpha, but not by the TP beta, isoform of the human TP and impaired the farnesylation-dependent processing of the chaperone HDJ-2 protein (IC(50) 4.5 nm). Furthermore, R115777 fully impaired isoprenylation of both the Ha-Ras(WT) and Ha-Ras(CSLC) in vitro and in whole cells confirming that, unlike N-Ras and Ki-Ras, the -CSLC motif associated with the IP cannot support alternative geranylgeranylation in the presence of R115777 and does not act as a substrate for geranylgeranyl transferase 1 in vitro or in whole cells. In conclusion, these data confirm that R115777 potently impairs IP isoprenylation and signalling, and suggest that clinically it may not only target Ras proteins but may also disrupt IP isoprenylation, events which could impact on physiologic processes in which prostacyclin and its receptor are implicated.