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

Date
2017-06-24
Authors
Frank, Annika
Abu-Lafi, Saleh
Adawi, Azmi
Schwed, Johannes S.
Stark, Holger
Rayan, Anwar
Journal Title
Journal ISSN
Volume Title
Publisher
Springer International Publishing AG
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, Gai2 and Gb1c2 subunits. Methods From the methanolic extract of C. longa curcumin (1), demethoxycurcumin (2) and bis(4-hydroxycinnamoyl) 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 Ki values of 4.26–6.26 lM (1.57–2.31 lg/mL) (1); 6.66––8.97 lM (2.26–3.04 lg/mL) (2) and 10.24–14.57 lM (3.16–4.49 lg/ mL) (3) (95% CI). The estimated Ki value of the crude extract of curcumawas 0.50–0.81 lg/mL. Fractionated curcumin and the crude extract surpassed the effect of pure curcumin with a Ki value of 5.54 lMor2.04 lg/mL[95%CI (4.47–6.86 lM), (1.65–2.53 lg/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.
Description
Keywords
Curcuma longa , Natural compounds , hH4R , Inflammatory diseases , Phenylpropanoids
Citation
Frank, A., Abu-Lafi, S., Adawi, A. et al. Inflamm. Res. (2017) 66: 923. https://doi.org/10.1007/s00011-017-1075-x