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

• Published in: Inflammation research 2017-10, Vol.66 (10), p.923-929
• Main Authors: Frank, Annika, Abu-Lafi, Saleh, Adawi, Azmi, Schwed, Johannes S., Stark, Holger, Rayan, Anwar
• Format: Article
• Language: English
• Subjects: Allergology; Biomedical and Life Sciences; Biomedicine; Dermatology; Immunology; Neurology; Original Research Paper; Pharmacology/Toxicology; Rheumatology
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-017-1075-x

Objectives The aim was to evaluate the activity of seven medicinal, anti-inflammatory plants at the hH 4 R with focus on defined chemical compounds from Curcuma longa . Materials Activities were analyzed with membrane preparations from Sf9 cells, transiently expressing the hH 4 R, 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 hH 4 R. Results Compounds from C. longa were the most potent ligands at the hH 4 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 hH 4 R. The mode of anti-inflammatory action of curcumin was further elucidated and the role of extracts in traditional phytomedicine was strengthened.