Inhibitory Effects of Usnic and Carnosic Acid on Some Metabolic Enzymes: An in vitro Study

Abstract

Background: Natural products arc produced via primary and secondary metabolism in different organisms. The compounds obtained via secondary metabolism are not essential for the survival of the organism, but they can have a different value for humans. Objective: The objective of this study was to examine inhibitory effects of Usnic Acid (UA), a well-known lichen secondary metabolite, and Carnosic Acid (CA), the primary antioxidant compound of Rosmarinus officinalis L., on purified Human Paraoxonase, (PON1), Glutathione Reductase (GR) and Glutathione S-Transferase (GST). These enzymes have antioxidant properties and a protective effect on the oxidation of free radicals. Hence, deficiencies of such enzymes inside cells can result in a buildup of toxic substances and cause some metabolic disorders. Methods: UA and CA were tested in various concentrations against human GST, PON1, and GR activity in vitro and they reduced human GST. PON1. and GR activity. Results: UA K-i constants were calculated as 0.012 +/- 0.0019, 0.107 +/- 0.06 and 0.21 +/- 0.1 mM for GST, PON1, and GR enzymes. CA K-i constants were determined as 0.028 +/- 0.009, 0.094 +/- 0.03 and 0.79 +/- 0.33 mM, for GST, PON1, and GR enzymes. UA and CA showed competitive inhibition for GR and GST enzymes, while they exhibited non-competitive inhibition for PON1. Conclusion: These findings indicate that UA and CA could be useful in drug development studies.