Background:
Natural products are 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 Ki 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 Ki 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.
Reactive oxygen species (ROS) are highly reactive and oxygen-containing molecules that are derived by metabolic activities or from environmental sources. Toxicity of heavy metals including iron has the ability to generate ROS in all living organisms. The pentose phosphate pathway enzymes, which are glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, produce nicotinamide adenine dinucleotide phosphate (NADPH) that enables cells to counterbalance the oxidative stress via the action of the glutathione system. The results presented here have shown that toxic and nontoxic levels of iron have a strong effect on the expression of both genes. While toxic levels of iron exhibited significant changes in enzyme activity, nontoxic levels had no effect on enzymes in rat liver. Our results are the first evidence to elucidate how oxidative stress induced by long-term iron toxicity affects both enzymes at the enzymatic and molecular level and also to determine any possible correlation between the enzymatic and molecular levels.
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