title: A Metabolomic Approach to Target Compounds from the Asteraceae Family for Dual COX and LOX Inhibition.
abstract: The application of metabolomics in phytochemical analysis is an innovative strategy for targeting active compounds from a complex plant extract. Species of the Asteraceae family are well-known to exhibit potent anti-inflammatory (AI) activity. Dual inhibition of the enzymes COX-1 and 5-LOX is essential for the treatment of several inflammatory diseases, but there is not much investigation reported in the literature for natural products. In this study, 57 leaf extracts (EtOH-H2O 7:3, v/v) from different genera and species of the Asteraceae family were tested against COX-1 and 5-LOX while HPLC-ESI-HRMS analysis of the extracts indicated high diversity in their chemical compositions. Using O2PLS-DA (R2 > 0.92; VIP > 1 and positive Y-correlation values), dual inhibition potential of low-abundance metabolites was determined. The O2PLS-DA results exhibited good validation values (cross-validation = Q2 > 0.7 and external validation = P2 > 0.6) with 0% of false positive predictions. The metabolomic approach determined biomarkers for the required biological activity and detected active compounds in the extracts displaying unique mechanisms of action. In addition, the PCA data also gave insights on the chemotaxonomy of the family Asteraceae across its diverse range of genera and tribes.
authors.affiliation: University of Strathclyde, the John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, UK. febcosta@fcfrp.usp.br.|School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Department of Pharmaceutical Sciences, Av. Café s/n, Ribeirão Preto-SP 14040-903, Brazil. febcosta@fcfrp.usp.br.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Chagas-Paula
authors.affiliation: University of Strathclyde, the John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, UK. tong.zhang.101@strath.ac.uk.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Department of Pharmaceutical Sciences, Av. Café s/n, Ribeirão Preto-SP 14040-903, Brazil. febcosta@fcfrp.usp.br.
authors.forename: Fernando B
authors.initials: FB
authors.lastname: Da Costa
authors.affiliation: University of Strathclyde, the John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, UK. ruangelie.edrada-ebel@strath.ac.uk.
authors.forename: RuAngelie
authors.initials: R
authors.lastname: Edrada-Ebel
keywords: Asteraceae; COX; HPLC-ESI-HRMS; LOX; O2PLS; metabolomics