The extracts from Nelumbo nucifera suppress cell cycle progression, cytokine genes expression, and cell proliferation in human peripheral blood mononuclear cells

In the hope of identifying agents of therapeutic value in tissue inflammation, we tested ethanolic extracts of six Chinese herbs for their effects on human peripheral blood mononuclear cells (PBMC) proliferation in vitro. The results indicated that the extracts from Nelumbo nucifera Gaertn, used in treatment of tissue inflammation in traditional Chinese medicine, inhibited PBMC proliferation activated with phytohemagglutinin (PHA). By a bioassay-guided fractionation procedure, NN-B-4 identified from N. nucifera ethanolic extracts significantly suppressed activated PBMC proliferation. The inhibitory action of NN-B-4 did not involve direct cytotoxicity. In an attempt to further localize the point in the PBMC proliferation where arrest occurred, a set of key regulatory events leading to the cell proliferation, including cell cycle progression, production and gene expression of interleukin-2 (IL-2), IL-4, IL-10, and interferon-gamma (IFN-gamma) was examined. Cell cycle analysis indicated that NN-B-4 arrested the cell cycle progression of activated PBMC from the G1 transition to the S phase. The cyclin-dependent kinase (cdk) 4 mRNA expression in PBMC stimulated with PHA was reduced by NN-B-4. NN-B-4 suppressed, in activated PBMC, the production and mRNA expression of IL-2, IL-4, IL-10, and IFN-gamma in a dose-dependent fashion. The suppressant effects of NN-B-4 on proliferation of PBMC activated by PHA therefore appear to be mediated, at least in part, through inhibition of early transcripts of PBMC, especially those of important IL-2, IFN-gamma, and cdk4 and arrest of cell cycle progression in the cells. (C) 2004 Published by Elsevier Inc.