From medicinal plant extracts to defined chemical compounds targeting the histamine H₄ receptor: Curcuma longa in the treatment of inflammation

Abstract

Objectives

The aim was to evaluate the activity of seven medicinal, anti-inflammatory plants at the hH₄R with focus on defined chemical compounds from Curcuma longa.

Materials

Activities were analyzed with membrane preparations from Sf9 cells, transiently expressing the hH₄R, G_αi2 and G_β1γ2 subunits.

Methods

From the methanolic extract of C. longa curcumin (1), demethoxycurcumin (2) and bis(4-hydroxy-cinnamoyl)methane (3) were isolated, purified with HPLC (elution-time 10.20, 9.66, 9.20 min, respectively) and together with six additional extracts, were characterized via radioligand binding studies at the hH₄R.

Results

Compounds from C. longa were the most potent ligands at the hH₄R. They exhibited estimated K _i values of 4.26–6.26 µM (1.57–2.31 µg/mL) (1); 6.66––8.97 µM (2.26–3.04 µg/mL) (2) and 10.24–14.57 µM (3.16–4.49 µg/mL) (3) (95% CI). The estimated K _i value of the crude extract of curcuma was 0.50–0.81 µg/mL. Fractionated curcumin and the crude extract surpassed the effect of pure curcumin with a K _i value of 5.54 µM or 2.04 µg/mL [95% CI (4.47–6.86 µM), (1.65–2.53 µg/mL)].

Conclusion

Within this study, defined compounds of C. longa were recognized as potential ligands and reasonable lead structures at the hH₄R. The mode of anti-inflammatory action of curcumin was further elucidated and the role of extracts in traditional phytomedicine was strengthened.