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Comparative Study
. 2003 Dec;26(12):1087-95.
doi: 10.1007/BF02994763.

Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages

Yunha Yun  1 , Shinha Han, Eunjung Park, Dongsool Yim, Sookyeon Lee, Chong-Kil Lee, Kyunghae Cho, Kyungjae Kim
Affiliations
Comparative Study

Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages

Yunha Yun et al. Arch Pharm Res. 2003 Dec.

Abstract

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, interleukin-1beta (IL-1beta) and the tumor necrosis factor-alpha (TNF-alpha) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-alpha and IL-1beta were produced by BA in a dose dependent manner at concentration of 0.625 and 10 microg/mL. The production of NO associated with iNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 microg/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 microg/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625 to approximately 5 microg/mL with or without LPS. Furthermore, BA (20 microg/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.

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