Potentiation of natural killer (NK) cell activity by methanol extract of cultured cambial meristematic cells of wild ginseng and its mechanism.

AIMS: As an alternative strategy to obtain large amounts of ginseng extract with high yield of ginsenosides, we have utilized culture of cambial meristematic cells (CMCs) from wild ginseng. The anti-tumor effects of methanol extract of ginseng CMCs (MEGC) and their action mechanisms were investigated. MAIN METHODS: Mice were intraperitoneally administered with MEGC, and we explored NK cell activity, suppression of in vivo growth of tumor cells and relevant molecule expression. KEY FINDINGS: MEGC significantly potentiated NK cell activity and suppressed in vivo growth of B16 melanoma cells. However, we observed no increase in NK cell number and unaltered expression of NK cell-activating (NKG2D) and inhibitory (Ly49, CD94/NKG2A) receptors as well as NK cell activation markers (CD25, CD69, CD119, and CD212) in MEGC-treated group compared to the controls. Instead, MEGC significantly enhanced IL-2 responsiveness in the early effector phase and the constitutive expression of granzyme B. SIGNIFICANCE: Our data indicate that culture of CMCs is an attractive alternative method for sustainable production of ginseng extracts and clinical use. In addition, we have unraveled a novel mechanism underlying the potentiation of NK cell activity and antitumor effect of ginseng extract, in which it upregulates the constitutive expression of cytotoxic mediator(s) and IL-2 responsiveness.

In vitro immunomodulatory activity of Bo-yang-hwan-o-tang.

Bo-yang-hwan-o-tang (BHT), an herbal decoction has been mainly used for improvement of blood flow in oriental medicine. Its in vivo immunomodulation was recently demonstrated but the effective mechanisms have not been described. This study was carried out to evaluate in vitro immunomodulatory activity of BHT. Water extract of BHT significantly promoted in vitro proliferative responses of mouse spleen cells (SPC) and also further enhanced the proliferation of SPC stimulated with anti-CD3 antibody. Unexpectedly, addition of BHT extract did not affect proliferation of both resting and CD3-activated T cells, whereas it showed a strong mitogenic activity on B cells. Flow cytometric analysis of CFSE-stained SPC showed that BHT-mediated enhancement of CD3-activated SPC proliferation is due to T cell, but not B cell, division. Mixed culture experiment combining T and mitomycin C-treated B cells demonstrated that BHT-mediated enhancement of CD3-activated T cell proliferation was dependent on the presence of B cells. However, B cell-derived factors were not involved in BHT effect on T cell proliferation. In the presence of B cells, BHT treatment resulted in a great enhancement in IL-2 production of CD3-activated T cells, and BHT effect on T cell proliferation was completely abrogated by addition of exogenous IL-2, indicating that IL-2 plays a critical role in BHT-mediated enhancement of CD3-activated T cell proliferation. Taken together, our data revealed that BHT possesses a potent B cell mitogenic activity and also can enhance activated T cell response through B cell regulation.