Cucurbitacin B inhibits immunomodulatory function and the inflammatory response in macrophages

Cucurbitacin B (CuB) is a triterpenoid that is widely distributed in the plant kingdom and has a variety of biological activities. However, the immunomodulatory and anti-inflammatory effects of CuB have not been well characterized. Therefore, in this study, we investigated the effects of CuB on parameters related to antigen presentation and T-cell activation. Specifically, we examined the effects of CuB on basal and lipopolysaccharide (LPS)-induced expression of class I and II MHC molecules, CD40, CD54, CD80, and CD86 in peritoneal macrophages. The LPS-a expression of MHC II, CD40, CD54, and CD80 was significantly attenuated by CuB. However, expression levels of MHC I and CD86 were not changed by CuB. CuB inhibited the production of intracellular reactive oxygen species induced by LPS and blocked the LPS-activated release of pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-6, IL-12, and IL-1β, without any cytotoxicity. Consistent with this, CuB also reduced the expression levels of inducible NO synthase and cyclooxygenase-2 induced by LPS. Furthermore, we demonstrated that the anti-inflammatory effects of CuB were dependent on the induction of heme oxygenase-1 expression via Nrf2 activation. Taken together, these data indicate that CuB possesses immunomodulatory and anti-inflammatory effects, and it may be used as an effective herbal remedy for the treatment and prevention of inflammation.