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From medicinal plant extracts to defined chemical compounds targeting the histamine H 4 receptor: Curcuma longa in the treatment of inflammation.

OBJECTIVES: The aim was to evaluate the activity of seven medicinal, anti-inflammatory plants at the hH4 R with focus on defined chemical compounds from Curcuma longa.

MATERIALS: Activities were analyzed with membrane preparations from Sf9 cells, transiently expressing the hH4 R, Gαi2 and Gβ1γ2 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 hH4 R.

RESULTS: Compounds from C. longa were the most potent ligands at the hH4 R. 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 hH4 R. The mode of anti-inflammatory action of curcumin was further elucidated and the role of extracts in traditional phytomedicine was strengthened.

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