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

Chagas-Paula DA, Zhang T, Da Costa FB, Edrada-Ebel R - Metabolites (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Strathclyde, the John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, UK. febcosta@fcfrp.usp.br.

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.

No MeSH data available.


Related in: MedlinePlus

Examples of phenolic compounds dereplicated from Asteraceae extracts with dual inhibition property against COX-1 and 5-LOX.
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metabolites-05-00404-f006: Examples of phenolic compounds dereplicated from Asteraceae extracts with dual inhibition property against COX-1 and 5-LOX.

Mentions: With the data provided by HPLC-UV-ESI-HRMS, the identification of the biomarkers was not as straightforward as the dereplication of the major compounds (Table 2) from the extracts. Due to the weak MS and UV responses of biomarkers, it is more likely that these metabolites were present as minor components in the extracts (Table S1). As presented in Table 3, by using the predicted molecular formulae, a huge number of isomers gave matching hits from SciFinder and DNP databases. However, special attention was given to compounds isolated within the Asteraceae family or within its genera. In the negative ESI mode, hits consisted mostly of phenolic and flavonoid compounds (Table 3, Figure 6), which have been previously described inseveral species within the family, and in these conditions, their peaks were observed between 15 to 20 min. The MF of C24H24O11 (ID#2054),detected in the ESI negative mode, matched acacetin-7-O-β-d-(3′′-acetyl)-glucopyranoside and was the only hit associated with the Asteraceae family [78]. This flavone glucoside was earlier isolated from the flowers of Chrysanthemum sinense Sabine and was reported to exhibit significant xanthine oxidase inhibitory activity. Interestingly, the kinetic study indicated a competitive-type of inhibition while at the same time acacetin-7-O-β-d-(3′′-acetyl)-glucopyranoside showed a mixed-type inhibition. Flavonoids are known to potentially deter inflammatory pathways [30,31,79] but none of these compounds have been described to specifically inhibit COX-1 and 5-LOX.


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

Chagas-Paula DA, Zhang T, Da Costa FB, Edrada-Ebel R - Metabolites (2015)

Examples of phenolic compounds dereplicated from Asteraceae extracts with dual inhibition property against COX-1 and 5-LOX.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588803&req=5

metabolites-05-00404-f006: Examples of phenolic compounds dereplicated from Asteraceae extracts with dual inhibition property against COX-1 and 5-LOX.
Mentions: With the data provided by HPLC-UV-ESI-HRMS, the identification of the biomarkers was not as straightforward as the dereplication of the major compounds (Table 2) from the extracts. Due to the weak MS and UV responses of biomarkers, it is more likely that these metabolites were present as minor components in the extracts (Table S1). As presented in Table 3, by using the predicted molecular formulae, a huge number of isomers gave matching hits from SciFinder and DNP databases. However, special attention was given to compounds isolated within the Asteraceae family or within its genera. In the negative ESI mode, hits consisted mostly of phenolic and flavonoid compounds (Table 3, Figure 6), which have been previously described inseveral species within the family, and in these conditions, their peaks were observed between 15 to 20 min. The MF of C24H24O11 (ID#2054),detected in the ESI negative mode, matched acacetin-7-O-β-d-(3′′-acetyl)-glucopyranoside and was the only hit associated with the Asteraceae family [78]. This flavone glucoside was earlier isolated from the flowers of Chrysanthemum sinense Sabine and was reported to exhibit significant xanthine oxidase inhibitory activity. Interestingly, the kinetic study indicated a competitive-type of inhibition while at the same time acacetin-7-O-β-d-(3′′-acetyl)-glucopyranoside showed a mixed-type inhibition. Flavonoids are known to potentially deter inflammatory pathways [30,31,79] but none of these compounds have been described to specifically inhibit COX-1 and 5-LOX.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Strathclyde, the John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, UK. febcosta@fcfrp.usp.br.

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.

No MeSH data available.


Related in: MedlinePlus