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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

Trend bar graphs indicating the peak areas of some of the biomarkers of dual inhibition of COX-1 and 5-LOX (positive mode HPLC-ESI-HRMS). The graphs are arranged in the order of decreasing correlation values. The graph for biomarker #1436 was omitted because it was quite similar to the graph of biomarker#1273 (Table S1). Extracts were colored as follows: Yellow for dual inhibitors, white for COX-1, grey for non-inhibitors, and pink for 5-LOX inhibitors (Table 1).
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metabolites-05-00404-f010: Trend bar graphs indicating the peak areas of some of the biomarkers of dual inhibition of COX-1 and 5-LOX (positive mode HPLC-ESI-HRMS). The graphs are arranged in the order of decreasing correlation values. The graph for biomarker #1436 was omitted because it was quite similar to the graph of biomarker#1273 (Table S1). Extracts were colored as follows: Yellow for dual inhibitors, white for COX-1, grey for non-inhibitors, and pink for 5-LOX inhibitors (Table 1).

Mentions: The dual inhibition biomarkers with the highest VIP scores (#2054 and #3913 detected in negative mode, #1637 and #1623 detected in positive mode) were found at higher concentrations only in dual inhibitor extracts (Figure 9 and Figure 10). However, the active samples do not have all these biomarkers together (Figure 9 and Figure 10).This may suggest that each of these compounds are single-handedly responsible for the dual inhibition of COX-1 and 5-LOX, and that the respective bioactive compounds do not depend on each other to be more or less active. In fact, we proved that the biomarker #1637 (tagitinin F), determined in two different approaches, is in fact able to inhibit both enzymes in vitro. Some of the biomarkers were also found to occur in extracts belonging to other AI property classes defined in this study. As shown in Figure 9 and Figure 10, the intensity of the biomarkers for dual inhibition was generally higher when compared to their incidence in inactive extracts. The occurrence of phenolic and flavonoid biomarkers (Table 3) was more dispersed throughout the different AI property classes, particularly for components ID#694, 2488, and 5001.


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)

Trend bar graphs indicating the peak areas of some of the biomarkers of dual inhibition of COX-1 and 5-LOX (positive mode HPLC-ESI-HRMS). The graphs are arranged in the order of decreasing correlation values. The graph for biomarker #1436 was omitted because it was quite similar to the graph of biomarker#1273 (Table S1). Extracts were colored as follows: Yellow for dual inhibitors, white for COX-1, grey for non-inhibitors, and pink for 5-LOX inhibitors (Table 1).
© Copyright Policy
Related In: Results  -  Collection

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

metabolites-05-00404-f010: Trend bar graphs indicating the peak areas of some of the biomarkers of dual inhibition of COX-1 and 5-LOX (positive mode HPLC-ESI-HRMS). The graphs are arranged in the order of decreasing correlation values. The graph for biomarker #1436 was omitted because it was quite similar to the graph of biomarker#1273 (Table S1). Extracts were colored as follows: Yellow for dual inhibitors, white for COX-1, grey for non-inhibitors, and pink for 5-LOX inhibitors (Table 1).
Mentions: The dual inhibition biomarkers with the highest VIP scores (#2054 and #3913 detected in negative mode, #1637 and #1623 detected in positive mode) were found at higher concentrations only in dual inhibitor extracts (Figure 9 and Figure 10). However, the active samples do not have all these biomarkers together (Figure 9 and Figure 10).This may suggest that each of these compounds are single-handedly responsible for the dual inhibition of COX-1 and 5-LOX, and that the respective bioactive compounds do not depend on each other to be more or less active. In fact, we proved that the biomarker #1637 (tagitinin F), determined in two different approaches, is in fact able to inhibit both enzymes in vitro. Some of the biomarkers were also found to occur in extracts belonging to other AI property classes defined in this study. As shown in Figure 9 and Figure 10, the intensity of the biomarkers for dual inhibition was generally higher when compared to their incidence in inactive extracts. The occurrence of phenolic and flavonoid biomarkers (Table 3) was more dispersed throughout the different AI property classes, particularly for components ID#694, 2488, and 5001.

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