Zerumbone from Zingiber zerumbet inhibits innate and adaptive immune responses in Balb/C mice

Abstract

Zerumbone exhibited various biological properties including in vitro immunosuppressive effects. However, its modulatory activity on the immune responses in experimental animal model is largely unknown. This in vestigation was conducted to explore the effects of daily treatment of zerumbone (25, 50, and 100 mg/kg) isolated from Zingiber zerumbet rhizomes for 14 days on various cellular and humoral immune responses in Balb/ C mice. For measurement of adaptive immunity, sheep red blood cells (sRBC) were used to immunize the mice on day 0 and orally fed with similar doses of zerumbone for 14 days. The effects of zerumbone on phagocytosis, nitric oxide (NO) release, myeloperoxidase (MPO) activity, proliferation of T and B cells, lymphocyte pheno typing, cytokines release in serum by activated T cells, delayed type hypersensitivity (DTH) and im munoglobulins production (IgG and IgM) were investigated. Zerumbone downregulated the engulfment of E. coli by peritoneal macrophages and the release of NO and MPO in a concentration-dependent manner. Zerumbone showed significant and concentration-dependent suppression of T and B lymphocytes proliferation and inhibi tion of the Th1 and Th2 cytokines release. At higher concentrations of zerumbone, the % expression of CD4+ and CD8+ in splenocytes was significantly inhibited. Zerumbone also concentration-dependently demonstrated strong suppression on sRBC-triggered swelling of mice paw in DTH. Substantial suppression of anti-sRBC im munoglobulins antibody titer was noted in immunized and zerumbone-treated mice in a concentration-depen dent manner. The potent suppressive effects of zerumbone on the immune responses suggest that zerumbone can be a potential candidate for development of immunosuppressive agent