Inhibition of lipoxygenase by sesamol corroborates its potential anti-inflammatory activity

Reactive oxygen species, the byproducts of oxygenases reaction, when in excess, promote degenerative diseases like cardiovascular, cancer and arthritis. Sesame lignans- sesamin, sesamolin and the phenolic degradation product of sesamolin, sesamol, are empirically known for their health promoting properties like antioxidant, antimutagenic, antiaging and antiinflammatory activities. In the current study, the effect of sesamol on the inflammatory oxygenase - lipoxygenase (LOX) was investigated. Enzyme kinetics and spectroscopic techniques were used to understand the inhibition mechanism. Sesamol was a potent inhibitor of soy LOX-1. It inhibited soy LOX-1 in a dose dependent manner with IC50 value of 51.84 μM and Ki of 4.9 μM. Binding studies using circular dichroism and corroborated by surface plasmon resonance, revealed that sesamol does not bind or change the conformation of LOX. Further, sesamol prevented the conversion of inactive LOX (Fe2+) to active LOX (Fe3+) by arresting the oxidation state of iron and prolonging the lag phase by virtue of its ability to scavenge hydroperoxides. Understanding the mechanism of action of such molecules will help in their application and promotion as nutraceuticals.