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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

Some sesquiterpene lactones dereplicated from extracts with dual inhibition property against COX-1 and 5-LOX (stereochemistry was not shown due to the possibility of occurrence of isomers/epimers, except for tagitinin F which was confirmed through co-elution and MS/MS fragmentation of a reference standard; Figure 8). Although it should be taken into account that all STLs from the tribes investigated herein (and those shown below) must have α,β orientation at C6/C7.
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metabolites-05-00404-f007: Some sesquiterpene lactones dereplicated from extracts with dual inhibition property against COX-1 and 5-LOX (stereochemistry was not shown due to the possibility of occurrence of isomers/epimers, except for tagitinin F which was confirmed through co-elution and MS/MS fragmentation of a reference standard; Figure 8). Although it should be taken into account that all STLs from the tribes investigated herein (and those shown below) must have α,β orientation at C6/C7.

Mentions: The positive mode revealed the presence of sesquiterpene lactones (STLs) and/or diterpenes that are relatively more non-polar eluting between 20 and 35 min (Table 3). Hits included STLs previously isolated from Tithonia diversifolia and Viguiera robusta as well as three different STLs described for the genera Viguiera and Vernonia (Table 3, Figure 7).T. diversifolia and V. robusta were among the extracts that exhibited dual inhibition against the enzymes COX-1 and 5-LOX. The presence of tagitinin F, which was earlier isolated from T. diversifolia, was then verified by co-elution and MS/MS fragmentation analysis (Figure 7 and Figure 8). The common peak eluting at 28.2 min in the dual inhibitor extracts #40–42, 49, 56, 59 and 60 (Table 1) yielded anion peak at m/z 349.1643 [M+H]+ and gave a similar MS/MS fragmentation pattern.MS/MS ion peaks were observed at m/z 331.1643 [M−H2O]+; 261.1116 [M−iBu]+; 243.1014[M−iBu−H2O]+; and 215.1063 [M−iBu−H2O−CO]+, which confirmed the identity of the peak (ID#1637) to be tagitinin F (Figure 8). Tagitinin F was evaluated for the first time and also showed to be a dual inhibitor of COX-1 and 5-LOX with IC50 values of 0.001 and 18.5 µM, respectively. It is worth mentioning that tagitinin F (ID#1637, Table 3) was also detected as a dual inhibitor of COX-1 and 5-LOX using the J48 decision tree classifier [28]. It should be emphasized that tagitinin F is not the major compound in leaves of T. diversifolia [7].These findings reveal the quality of our developed metabolomics-based approaches to detect biologically active compounds in extracts.


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)

Some sesquiterpene lactones dereplicated from extracts with dual inhibition property against COX-1 and 5-LOX (stereochemistry was not shown due to the possibility of occurrence of isomers/epimers, except for tagitinin F which was confirmed through co-elution and MS/MS fragmentation of a reference standard; Figure 8). Although it should be taken into account that all STLs from the tribes investigated herein (and those shown below) must have α,β orientation at C6/C7.
© Copyright Policy
Related In: Results  -  Collection

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

metabolites-05-00404-f007: Some sesquiterpene lactones dereplicated from extracts with dual inhibition property against COX-1 and 5-LOX (stereochemistry was not shown due to the possibility of occurrence of isomers/epimers, except for tagitinin F which was confirmed through co-elution and MS/MS fragmentation of a reference standard; Figure 8). Although it should be taken into account that all STLs from the tribes investigated herein (and those shown below) must have α,β orientation at C6/C7.
Mentions: The positive mode revealed the presence of sesquiterpene lactones (STLs) and/or diterpenes that are relatively more non-polar eluting between 20 and 35 min (Table 3). Hits included STLs previously isolated from Tithonia diversifolia and Viguiera robusta as well as three different STLs described for the genera Viguiera and Vernonia (Table 3, Figure 7).T. diversifolia and V. robusta were among the extracts that exhibited dual inhibition against the enzymes COX-1 and 5-LOX. The presence of tagitinin F, which was earlier isolated from T. diversifolia, was then verified by co-elution and MS/MS fragmentation analysis (Figure 7 and Figure 8). The common peak eluting at 28.2 min in the dual inhibitor extracts #40–42, 49, 56, 59 and 60 (Table 1) yielded anion peak at m/z 349.1643 [M+H]+ and gave a similar MS/MS fragmentation pattern.MS/MS ion peaks were observed at m/z 331.1643 [M−H2O]+; 261.1116 [M−iBu]+; 243.1014[M−iBu−H2O]+; and 215.1063 [M−iBu−H2O−CO]+, which confirmed the identity of the peak (ID#1637) to be tagitinin F (Figure 8). Tagitinin F was evaluated for the first time and also showed to be a dual inhibitor of COX-1 and 5-LOX with IC50 values of 0.001 and 18.5 µM, respectively. It is worth mentioning that tagitinin F (ID#1637, Table 3) was also detected as a dual inhibitor of COX-1 and 5-LOX using the J48 decision tree classifier [28]. It should be emphasized that tagitinin F is not the major compound in leaves of T. diversifolia [7].These findings reveal the quality of our developed metabolomics-based approaches to detect biologically active compounds in extracts.

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