Immunomodulatory Effects of Combined Ethanol Extracts of Curcuma mangga and Picria fel-terrae on Cellular- and Humoral-Mediated Immunity in Wistar Rats and Mice

Previous studies have shown that the extracts of Curcuma mangga Valeton & Zijp rhizomes and Picria fel-terrae Lour. leaves could modulate cellular- and humoral-mediated immunity in macrophages and animal models. In the present study, the immunomodulatory effects of combined ethanol extracts of C. mangga rhizomes and P. fel-terrae leaves were investigated on cellular- and humoral-mediated immunity in Wistar rats and mice. The phytochemical constituents of the ethanol extracts of C. mangga and P. fel-terrae, and combined extracts were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Mice were orally administered with combined extracts of C. mangga and P. fel-terrae (1 : 1) at doses of 25, 50, and 100 mg/kg·bw for 7 days, and the carbon clearance method was used to investigate their phagocytosis activity. Wistar rats were treated orally with the combined extracts 72 h prior to sensitization with Staphylococcus aureus and continued for 14 days. The effect of extracts on delayed-type hypersensitivity (DTH) response was determined by the paw edema method, while the effects on antibody (IgG and IgM) and interleukin-2 (IL-2) production were analyzed using enzyme-linked immunosorbent assay (ELISA). Picfeltarraenin VI and ferruginol were the major components in the extracts of P. fel-terrae and C. mangga, respectively. The combined extracts at 1 : 1 ratio demonstrated a dose-dependent stimulation of both cellular- and humoral-mediated immunity in both animal models. The combined extracts displayed the strongest stimulation on DTH response and phagocytosis activity at 100 mg/kg·bw, which were comparable with those of the positive control, levamisole. IgG and IgM production and IL-2 release were also stimulated after treatment with extracts. The combined extracts of C. mangga and P. fel-terrae possess strong stimulatory activities on cellular- and humoral-mediated immunity and may be developed as a potential nutraceutical for the modulation of immune responses.