Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages
Yun, Y.; Han, S.; Park, E.; Yim, D.; Lee, S.; Lee, C-Kil.; Cho, K.; Kim, K.
FASEB Journal 18(4-5): Abstract 329
2004
ISSN/ISBN: 0892-6638 PMID: 14723345 Document Number: 581433
Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, Interlukin-1β (IL-1β) and the tumor necrosis factor-α (TNF-α) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-α and IL-1β were produced by BA in a dose dependent manner at concentration of 0.625 and 10 /ml. The production of NO associated with iNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 μg/ml of BA whereas COX-2 expression was decreased at 2.5 to 20 μg/ml. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and primary macrophages. The morphology of macrophage was also examined and enhanced surface CD40 molecule was expressed when treated BA at 0.625 - 5 μg/ml with or without LPS. Furthermore, BA (20 μg/ml) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.