Immunomodulation Exhibited by Piperinic Acid Through Suppression of Proinflammatory Cytokines

Piper longum (PL) has been reported for its varied pharmacological activities including bio-enhancer and anti-inflammatory activities in traditional medicine. Here the premise of the study was to investigate the immunoregulatory potential of PL and piperinic acid, one of its active constituent, in Balb/C mice (in vivo) and human PBMCs (in vitro) models. Piperinic acid moderated the proinflammatory mediators and cytokines in our experiments. At doses of 10, 20, 40 and 80 mg/kg p.o. PL showed a dose dependent decrease of lymphocytes (CD4+ and CD8+ T cells) and cytokine levels in sensitized Balb/C mice with a marked inhibition at 40 mg/kg. At an in vitro dose of 20 mug/ml of PL and 5 mug/ml of piperinic acid, there was a significant inhibition of mitogen induced human PBMC proliferation, mRNA transcripts of IL-2 (ConA) and TNFalpha, IL-1beta and iNOS (LPS) respectively under stimulated conditions in time dependent (6 h, 12 h and 24 h respectively) expression studies. In parallel, induced nitric oxide production was also reduced by stimulated macrophages. Our observations rationalize the traditional use of PL and also validate the immunoregulatory potential of piperinic acid.