CKBM stimulates MAPKs but inhibits LPS-induced IFN-gamma in lymphocytes.

CKBM is an herbal formula composed of five Chinese medicinal herbs (Panax ginseng, Schisandra chinensis, Fructus crataegi, Ziziphus jujuba and Glycine max) supplemented with processed Saccharomyces cerevisiae. It has been demonstrated that CKBM is capable of triggering the release of IL-6 and TNFalpha from human peripheral blood mononuclear cells. In this report, T-lymphocytic Sup-T1 cells and B-lymphocytic Ramos cells were utilized as cellular models to investigate how CKBM regulates intracellular signaling as well as the production of cytokines. CKBM stimulated the three major subgroups of mitogen-activated protein kinase (i.e. ERK, JNK and p38) in Sup-T1 cells, but only triggered the activation of ERK and p38 in Ramos cells. The induction of mitogen-activated protein kinases (MAPK) activations varied with the duration of treatment, as well as with the dosage of CKBM. In terms of cytokine production, treatment of CKBM alone did not trigger the release of IL-1beta and IFNgamma, but it suppressed the LPS-induced IFNgamma production from both Sup-T1 cells and Ramos cells. In view of the therapeutic effects of traditional Chinese medicines in inflammatory and autoimmune disorders, the results suggest that CKBM may exhibit its immuno-modulatory effects by regulating intracellular signaling as well as cytokine production in different lymphocytic cell types.

The aqueous extract of Radix Glycyrrhizae stimulates mitogen-activated protein kinases and nuclear factor-kappaB in Jurkat T-cells and THP-1 monocytic cells.

Radix Glycyrrhizae (RG) is a medicinal herb extensively utilized in numerous Chinese medical formulae for coordinating the actions of various components in the recipes and strengthening the body functions. In this report, we demonstrate that the aqueous extract of Radix Glycyrrhizae is capable of stimulating the c-Jun N-terminal kinase and p38 subgroups of mitogen-activated protein kinases (MAPKs), and the nuclear factor-kappaB (NFkappaB) in Jurkat T-lymphocytes. The activation magnitudes of MAPKs and NFkappaB were dose-dependent (EC(50) approximately 1 mg/ml) and time-dependent (maximal around 15-30 minutes). Stimulations of MAPKs and NFkappaB were not associated with changes in intracellular Ca(2+) mobilization. Similar activation profiles of MAPK and NFkappaB were obtained from THP-1 monocytes treated with the extract. In terms of chemotactic activity, the SDF-induced chemotaxis of Jurkat cells and THP-1 cells were inhibited by RG extract at 1-10 mg/ml, while a lower RG concentration (0.1-0.3 mg/ml) potentiated the SDF-induced chemotaxis for the former, but not the latter cell type. Given the fact that MAPKs and NFkappaB are important signaling intermediates for lymphocyte activities, our results suggest that Radix Glycyrrhizae may contain active constituents capable of modulating immuno-responses through various intracellular signaling pathways.

Carvacrol and eugenol differentially stimulate intracellular Ca2+ mobilization and mitogen-activated protein kinases in Jurkat T-cells and monocytic THP-1 cells.

Essential oils are a major active constituent found in many Chinese medicinal herbs. Here, we demonstrate that two components of essential oils, carvacrol and eugenol, dose-dependently trigger intracellular Ca2+ mobilization in Jurkat T-cells and THP-1 monocytic cells. Both carvacrol and eugenol are also capable of stimulating the active phosphorylation of the p38 subgroup of mitogen-activated protein kinases (MAPKs) in both cell types. However, carvacrol selectively activated the ERK subgroup in Jurkat T-cells, and stimulated the JNK subgroup in THP-1 monocytic cells. Eugenol treatment was not linked to ERK or JNK activation in either cell type. EC50 values for the induction of Ca2+ mobilization and MAPK activation were around 10 - 30 microM for both carvacrol and eugenol. Our results suggest that these essential oil components may act as effective agents to modulate the functions of immuno-responsive cells via different intracellular signaling pathways.