Inhibition of human dendritic cell activation by hydroethanolic but not lipophilic extracts of turmeric (Curcuma longa)

Abstract

Turmeric has been extensively utilized in Indian and Chinese medicine for its immune-modulatory properties. Dendritic cells (DCs) are antigen-presenting cells specialized to initiate and regulate immunity. The ability of DCs to initiate immunity is linked to their activation status. The effects of turmeric on human DCs have not been studied. Here we show that hydroethanolic (HEE) but not lipophilic "supercritical" extraction (SCE) of turmeric inhibits the activation of human DCs in response to inflammatory cytokines. Treatment of DCs with HEE also inhibits the ability of DCs to stimulate the mixed lymphocyte reaction (MLR). Importantly, the lipophilic fraction does not synergize with the hydroethanolic fraction for the ability of inhibiting DC maturation. Rather, culturing of DCs with the combination of HEE and SCE leads to partial abrogation of the effects of HEE on the MLR initiated by DCs. These data provide a mechanism for the anti-inflammatory properties of turmeric. However, they suggest that these extracts are not synergistic and may contain components with mutually antagonistic effects on human DCs. Harnessing the immune effects of turmeric may benefit from specifically targeting the active fractions.

Fig. 1

Hydroethanolic extracts (HEE) of turmeric inhibit maturation of human monocyte-derived DCs in response to inflammatory cytokines. (A) Monocyte-derived DCs were cultured with 10 μg/mL of turmeric extracts or controls for 2 h, prior to the addition of the inflammatory cytokine cocktail. After overnight culturing, the expression of CD80, CD86, and CD83 was monitored by flow cytometry. Data are representative of 4 separate experiments. Numbers represent mean fluorescent intensity. (B) Summary of experiments. *P < 0.05. (C) DCs were treated with hydroethanolic extracts or with curcumin (CCM) at 10μM, and the expression of CD80, CD86, and CD83 was monitored after the addition of inflammatory cytokines, as in Fig. 1A. *P < 0.05 compared with vehicle controls.

Fig. 2

Lack of synergy between HEE and SCE of turmeric. (A) DCs were cultured with 10 μg/mL of each extract separately or together, prior to activation with a cocktail of inflammatory cytokines (CC) as described in the methods. After overnight culturing, the expression of markers associated with DC maturation was analyzed by flow cytometry. Data are representative of 3 similar experiments. (B) Cytokine-matured DCs obtained from the cultures as in Fig. 2A were used to stimulate allogeneic lymphocytes. The proliferation of responding cells was analyzed based on tritium incorporation (CPM: counts per minute). Data are representative of two similar experiments.