Metabolomics approach provides new insights into the immunomodulatory discriminatory biomarkers of the herbs and roots of Echinacea species

Abstract

Echinacea species roots and aerial parts are considered among the most popular plants used worldwide for management of common cold and other upper respiratory infections. This study aims at revealing the immunomodulatory biomarkers amid the diverse metabolites in the roots and herbs of the most widely used Echinacea species; E. purpurea, E. angustifolia and E. pallida. UPLC-QqQ-MS-based metabolomic approach was implemented for comprehensive investigation of the relative amount of chemical constituents resulting in the identification of 56 metabolites. PCA and HCA revealed that E. angustifolia root was separately segregated from all other samples, with cynarin and 2-undecene-8,10-diynoic acid isobutylamide being the main secondary metabolites contributing to such a clustering pattern. Further, determination of immunomodulatory discriminatory metabolites among the tested roots and herbs of the three Echinacea species was attempted through construction of an OPLS-DA model which revealed that, with exception of E. pallida in which both roots and herbs were clustered together reflecting the similarity in their immunomodulatory activity, the roots of Echinacea species possessed similar immunomodulatory response in comparison to the herbs which were relatively less efficient as immunomodulators. Correlation analysis indicated that 8,11-dihydroxy-2,4,9-dodecatrienoic acid isobutylamide, dicaffeoyl quinic acid, echinacoside and 8-hydroxy-pentadeca-(9E,13Z)-dien-11-yn-2-one were positively correlated to upregulation of the RELA pathway while 2-undecene-8,10-diynoic acid isobutylamide, dodeca-2,4,8,10-tetraenoic acid isobutylamide and dicaffeoyl quinic acid, were positively correlated to the upregulation of NFKB1. The results also indicated that the immunomodulatory effect of polyenes is correlated to the upregulation of IL6 production and downregulation of RELA and NFKB1 pathways. Meanwhile, alkylamides immunomodulatory effect is correlated to upregulation of IL6, NFKB1 and NO production.