Actividad supresora del millerenólido sobre células mononucleares de sangre periférica humana / Millerenolide induces suppressive activity on human peripheral blood mononuclear cells

Background: Natural products are used in the production of therapeutic drugs due to their wide diversity and excellent adaptability to biological structures. Sesquiterpene ¡aciones are the active constituents of several plants from the Asteraceae family. Aim: To assess the in vitro effect of a sesquiterpene lactone (millerenolide). Material and methods: The drug effect was assessed measuring the proliferation of lymphocytes using the 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonylJ-2H-tetrazolium hydroxide (XTT) technique. Changes on the cell cycle were analyzed on a FACSort flow cytometer The effect of millerenolide on the production of nitric oxide (NO) by macrophages was evaluated using the Griess reagent. Additionally, phagocytosis of latex particles and nitroblue tetrazolium (NBT) reduction by macrophages were evaluated microscopically. Results: Treatment of human peripheral blood mononuclear cells (PBMC) with millerenolide decreases the proliferation of lymphocytes, decreases the percentage of cells in S, and G2/Mphases, and increases the proportion of cells in GO/Gl phase. Treatment of macrophages with millerenolide, reduces the production of NO, the phagocytic capacity and the number of cells able to reduce NBT. Cytotoxic effects of the lactone on human PBMC were only observed when the concentration was increased to 6 fig/ml. Conclusions: Millerenolide could be considered as a potential therapeutic agent with immunosuppressiveproperties.

Effect of bacosides, alcoholic extract of Bacopa monniera Linn. (brahmi), on experimental amnesia in mice.

To investigate the effect of bacosides (alcoholic extract of brahmi) on scopolamine (3 mg kg(-1), ip), sodium nitrite (75 mg kg(-1), ip) and BN52021 (15 mg kg(-1), ip) induced experimental amnesia in mice, using Morris water maze test, all the agents were administered 30 min before the acquisition trials on each day and repeated for 4 consecutive days, and on 5th day during the retrieval trials. Bacosides on anterograde administration (before training) in mice, significantly decreased the escape latency time (ELT) during the acquisition trials for 4 consecutive days and increased the time spent (TS) in target quadrant during the retrieval trials on 5th day, and on retrograde administration (after training) bacosides were found not to affect TS significantly. Bacosides also significantly decreased the ELT and increased the TS in mice treated anterogradely with scopolamine and sodium nitrite. Bacosides did not exhibit any significant effect on TS of mice treated retrogradely with sodium nitrite. On the other hand, bacosides significantly increased the TS of mice treated retrogradely with BN52021. On the basis of the present results it can be concluded that bacosides facilitate anterograde memory and attenuate anterograde experimental amnesia induced by scopolamine and sodium nitrite possibly by improving acetylcholine level and hypoxic conditions, respectively. Beside this bacosides also reversed BN52021 induced retrograde amnesia, probably due to increase in platelet activating factor (PAF) synthesis by enhancing cerebral glutamate level.

Daño gastrointestinal inducido por celecoxib y rofecoxib, en ratas / Gastrointestinal damage induced by celecoxib and rofecoxib in rats

En diferentes grupos de ratas Wistar (n=15), se estudiaron AINEs inhibidores selectivos de la COX-2, como delecoxib y refecoxib, en cinco modelos experimentales: 1) Celecoxib y rofecoxib por vía oral y dosis dependiente durante 5 días y 24 hs. Después de indometacina oral. 2) Similar a 1, pero subcutáneo. 3) Ulcera gástrica inducida por ácido acético glacial. 4) Ulcera duodenal por cisteamina. 5) Estrés por inmovilización e inmersión en agua a 15 grados Celsius durante 6 horas. Celecoxib y rofecoxib por vía oral o SC en mucosa gastrointestinal sana no provaron lesiones necróticas en una superficie del 0 grados Celsius, presentanto histología normal; en cambio, agravaron y complicaron lesiones inducidas en forma previa por indometacina en más del 90 por ciento (p<0,001), con necrosis masiva del intestino delgado, así como ampliaron y causaron perforaciones en las úlceras gástricas y duodenales inducidas por ácido acético y cisteamina. Se produjo asimismo agravación de la zona necrótica gástrica por estrés en un 60-90 por ciento (p<0,05). Celecoxib y rofecoxib condujeron a una neutrofilia de 5000/mm3, similar a la inducida por la indometacina; en cambio, no produjeron infiltración leucocitaria en mucosa gástrica (MPO), siendo un marcador de AINE selectivo COX-2. Se concluyó que celecoxib y rofecoxib, administrados en dosis dependiente como inhibidores de COX-2 y no COX-1, no provocaron en mucosa gastrointestinal sana ninguna lesión por toxicidad, observándose un amplio margen terapéutico. En cambio, suministrados en mucosa gastrointestinal dañada agravaron y complicaron las lesiones ulcerosas gástricas y necróticas intestinales, limitando su uso en clínica.