Antiproliferative activity of Juglone derivatives on rat glioma

7nononenonePavan V.; Ribaudo G.; Zorzan M.; Redaelli M.; Pezzani R.; Mucignat-Caretta C.; Zagotto G.Pavan, V.; Ribaudo, G.; Zorzan, M.; Redaelli, M.; Pezzani, R.; Mucignat-Caretta, C.; Zagotto, G

Serotonin and Noradrenaline Reuptake Inhibitors Improve Micturition Control in Mice

<div><p>Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg), to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.</p></div

Transverse bladder sections stained with hematoxylin and eosin for mucosa thickness measurement.

<p>The bladder mucosa (UL: urothelium layer, LP: lamina propria) and the muscular layer (ML) are shown. Scale bar = 100 μm, 20X magnification. A and B: mucosa of a CYP-treated mouse in contact with the lumen at the top and the entire muscular layer at the bottom. A representative bladder section shows the morphology of the tissue (A) and the precise area in grey (B) corresponding with the urothelium, where its thickness was measured. C: thickness of the urothelium (μm) plotted across experimental groups. Control represents bladders of untreated mice, while all the other bars refer to CYP-treated mice, injected with saline or antidepressant. Data are presented as mean+SEM compared with control group, ANOVA and Duncan <i>post hoc</i> test * p<0.05, ** p<0.005, *** p<0.001, n = 7 for each experimental group.</p

Voiding behaviour of CYP-injected mice (n = 7) in comparison with a saline injected group (n = 5).

<p>A, B, C: data describing the micturition pattern: first voiding latency (A), urine volume (B) and number of urine spots (C). D: body weight during the experiment. E, F: Representative UV images of urinary spots of a control mouse (E) in comparison with a CYP-treated mouse (F). Data are presented as mean±SEM. ANOVA and Duncan <i>post hoc</i> test, *: p<0.05, **: p<0.005, ***: p<0.001.</p

Voiding behaviour of CYP-injected mice treated with saline or antidepressants.

<p>A, B, C: data describing the micturition pattern: first voiding latency (A), urine volume (B) and number of urine spots (C). Data are presented as mean+SEM. ANOVA and Duncan <i>post hoc</i> test (comparison with saline group) *: p<0.05, **: p<0.005, ***: p<0.001. D, E, F, G and H: representative UV images of urinary spots collected 48 hours after the beginning of the antidepressant treatment: control CYP-injected mouse (D), desipramine (E), imipramine (F) duloxetine (G) and 4-hydroxy-duloxetine-treated mouse (H). The images show a decrease in voiding behaviour in antidepressant-treated mice.</p

Biological activities of the aerial and undergound parts of <i>Gymnadenia nigra</i> Rchb.f. (syn. <i>Nigritella nigra</i> (L.) Rchb. f.) from the Italian Alps

This study investigated the bioactivity of both aerial (GNAR) and underground (GNUG) parts of Gymnadenia nigra Rchb.f. (syn. Nigritella nigra (L.) Rchb. f.) (Orchidaceae). The obtained data proved interesting when the samples were tested in two adrenocortical cancer cell lines (SW13 and H295R). In particular, the GNAR 80% methanol extract distinctly inhibited their viability after 24 h at a concentration of 1 µg/µL by MTT assay and trypan blue dye exclusion method. Cell morphology evaluation by means Wright’s staining also showed significant results, particularly in SW13 cells under the effect of both extracts. GNAR extract was able to scavenge the DPPH radical better than GNUG extract. It also was more active in albumin denaturation (a maximum % denaturation equal to 463.0 ± 8.3 vs 77.3 ± 13.3) and protease inhibition (a maximum % inhibition equal to 138.5 ± 7.0 vs 2.1 ± 2.0) tests. The results highlighted an important antitumor activity of G. nigra in vitro that deserves to be further studied.</p

Crude extract of <i>Origanum vulgare</i> L. induced cell death and suppressed MAPK and PI3/Akt signaling pathways in SW13 and H295R cell lines

<p>Oregano (<i>Origanum vulgare</i> L.) is a common aromatic plant used in Mediterranean and Asian Regions for treating respiratory diseases, painful menstruation, rheumatoid arthritis, etc. Recently its role as an anticancer plant has been suggested, although oregano has been never evaluated into adrenocortical tumour cell models. This study analysed for the first time the anticancer effects of a crude extract of wild mountain oregano (<i>Origanum vulgare</i> L.) in SW13 and H295R cell lines. The crude extract was characterised by GC/MS and the toxic effects of oregano were first analysed by brine shrimp lethality assay. Our findings demonstrated that oregano decreased cell viability, survival, modified cell cycle and induced cell death (through necrotic process) and that the effects can be attributed to a blockade of MAPK and PI3 K/Akt pathways. These results suggest that oregano extract exerts anticancer activities in adrenocortical tumour cell lines, providing evidence for further research in higher models.</p