D-pinitol inhibits Th1 polarization via the suppression of dendritic cells.
ABSTRACT d-pinitol has been demonstrated to exert insulin-like and anti-inflammatory effects. However, the effects of the maturation and immunostimulatory functions of dendritic cells (DC) remain to be clearly elucidated. In this study, we have attempted to determine whether d-pinitol regulates surface molecule expression, cytokine production, endocytosis capacity, and underlying signaling pathways in murine bone marrow-derived DC. We also attempted to ascertain whether d-pinitol could influence Th1/Th2 immune response in vivo. The DC used in this study were derived from murine bone marrow cells, and were used as immature or LPS-stimulated mature DC. The DC were then assessed with regard to surface molecule expression, dextran-FITC uptake, cytokine production, capacity to induce T-cell differentiation, and underlying signaling pathways. d-pinitol was shown to significantly inhibit CD80, CD86, MHC class I, and MHC class II expression in the LPS-stimulated mature DC. The DC also evidenced impaired IL-12 expression and IFN-gamma production. The d-pinitol-treated DC were found to be highly efficient in regards to Ag capture via mannose receptor-mediated endocytosis. d-pinitol was also demonstrated to inhibit LPS-induced MAPKs activation and NF-kappaB nuclear translocation. Moreover, the d-pinitol-treated DC manifested impaired induction of Th1 responses, and normal cell-mediated immune responses. These novel findings provide new insight into the immunopharmacological role of d-pinitol in terms of its effects on DC. These findings also broaden current perspectives concerning our understanding of the immunopharmacological functions of d-pinitol, and have ramifications for the development of therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.
Article: Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells.[show abstract] [hide abstract]
ABSTRACT: There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], flow cytometry, cytoskeleton organization analysis, cell cycle, mitochondria membrane depolarization, clonogenicity test, DNA fragmentation test and differential protein expression by HPLC-Chip/MS analysis. F4 fraction characterization was made by HPLC-MS. Petiveria alliacea fraction characterized by de-replication was found to alter actin cytoskeleton organization, induce G2 cell cycle arrest and cause apoptotic cell death in a mitochondria independent way. In addition, we found down regulation of cytoskeleton, chaperone, signal transduction proteins, and proteins involved in metabolic pathways. Finally up regulation of proteins involved in translation and intracellular degradation was also observed. The results of this study indicate that Petiveria alliacea exerts multiple biological activities in vitro consistent with cytotoxicity. Further studies in animal models are needed but Petiveria alliacea appears to be a good candidate to be used as an antitumor agent.BMC Complementary and Alternative Medicine 12/2008; 8:60. · 2.24 Impact Factor