Effects of sesquiterpene lactones on lipoxygenase activity

Sesquiterpene lactones (STL) are natural compounds with a wide structural variety and a broad array of biological activities. Some of these activities are related to the capacity of STL to modulate different enzymes by inhibition or induction of their activities¹. Lipoxygenase (LOX) is a ubiquitous enzyme that occurs in microorganisms, animals and plants. In these living organisms, LOX may display different functions depending on the products formed as a result of its reaction with fatty acids. In plants, for example, LOX acts on growth, development, senescence and defense by conversion of linoleic acid to jasmonic acid derivatives². In animals, LOX is mainly related to the inflammatory process by conversion of the arachidonic acid into eicosanoids. Thus, the aim of this work was to evaluate the potential of STL in the modulation of the LOX activities. So far, about 30 STL were isolated from different species of the family Asteraceae and 26 of them were tested in an in vitro assay for the inhibition of the 5-LOX isoform. The results show that 10 STL were active by inhibiting the enzyme at relatively low concentrations. The most effectives of them were chamisellin (IC₅₀= 0.18 µg/mL), polimatin B (IC₅₀= 1.91 µg/mL) and fluctuanin (IC₅₀= 2.02 µg/mL). These results suggest the STL have a potential use in the modulation of the LOX activity. Further studies will be carried out aiming to analyze structure-activity relationships.

Fig. 1: The most effective STL in the 5-LOX inhibition assay

Acknowledgements: FAPESP.

References:

[1] Tornhamre S. et al. 2001. Biochem. Pharmacol. 62: 903.

[2] Feussner I. et al. 1995. Proc. Natl. Acad. Sci. 92: 11849.