Cytoprotective and immunomodulating properties of piperine on murine splenocytes: an in vitro study.

Piper longum Linn. and Piper nigrum Linn. are conventionally used as immuno-enhancers in Indian system of traditional medicine. The underlying mechanism remains unknown. The present study was therefore, undertaken to delineate the role of piperine (major alkaloid) in cadmium (Cd) induced immuno-compromised murine splenocytes. The various biological determinants such as oxidative stress markers (reactive oxygen species and GSH), Bcl-2 protein expression, mitochondrial membrane potential, caspase-3 activity, DNA damage, splenic B and T cell population, blastogenesis and cytokines (Interleukin-2 and gamma-Interferon) were measured to ascertain its cell protective potential. Cadmium induces apoptosis at 6 h onwards. The oxidative stress markers markedly alter prior to a decline in mitochondrial membrane potential, caspase-3 activation and DNA degradation The splenic cell population was observed to change only at 18 h and the release of two cytokines was affected at 72 h. Addition of piperine in various concentrations (1, 10 and 50 microg/ml) ameliorated the above events. The highest dose of piperine could completely abrogate the toxic manifestations of cadmium and the splenic cells behaved similar to control cells. The reported free radical scavenging property of piperine and its antioxidant potential could be responsible for the modulation of intracellular oxidative stress signals. These in turn appear to mitigate the apoptotic pathway and other cellular responses altered by cadmium. The findings strongly indicate the anti-oxidative, anti-apoptotic and chemo-protective ability of piperine in blastogenesis, cytokine release and restoration of splenic cell population and is suggestive of its therapeutic usefulness in immuno-compromised situations.