A Metabolomic Approach to Target Compounds from the Asteraceae Family for Dual COX and LOX Inhibition

Autor(es)

Chagas-Paula, Daniela A. ^{[1, 2]} ; Zhang, Tong ^[2] ; Da Costa, Fernando B. ^[1] ; Edrada-Ebel, RuAngelie ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto FCFRP, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Strathclyde, John Arbuthnott Bldg, 161 Cathedral St, Glasgow G4 0RE, Lanark - Scotland

• Tipo de documento: Artigo Científico
• Fonte: METABOLITES; v. 5, n. 3, p. 404-430, SEP 2015.
• Citações Web of Science: 24

Resumo

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 (R-2 > 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 = Q(2) > 0.7 and external validation = P-2 > 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. (AU)

• Processo FAPESP: 10/10940-2 - Estudos metabolômicos de Asteraceae por CLAE-UV-EM, avaliação do potencial anti-inflamatório "in vitro" e suas correlações através de métodos "in silico".
• Beneficiário: Daniela Aparecida Chagas de Paula
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/51454-3 - Estudos morfoanatômicos, metabolômicos e moleculares como subsídios à sistemática de espécies de Asteraceae e acesso ao seu potencial farmacológico
• Beneficiário: Beatriz Appezzato da Glória
• Modalidade de apoio: Auxílio à Pesquisa - Temático