Effect of hydroalcoholic extract of Tanacetum parthenium on gene expression and paraoxonase ۱ enzyme activity: An experimental and molecular dynamic study

Background and aims: Cardiovascular diseases are among the most common causes of death worldwide. The paraoxonase ۱ (PON۱) enzyme is a main factor in preventing these diseases. This study investigated the effect of hydroalcoholic extract of Tanacetum parthenium plant on the activity and gene expression of PON۱. Methods: Forty male rats were divided into ۴ groups: a control group, a hyperlipidemic group, and two hyperlipidemic groups that were treated with ۴۰۰ and ۸۰۰ mg/kg of hydroalcoholic extract. Arylesterase activity of PON۱ and serum triglyceride and cholesterol levels were measured. Moreover, the gene expression of PON۱ in the liver tissue samples was measured using real-time PCR. Finally, molecular dynamics studies of apigenin as a main compound in the plant were performed to investigate the activity of PON۱ in the simulated environment. Results: Hydroalcoholic extract of T. parthenium decreased serum triglyceride (from ۱۰۵.۸±۱۰.۱ to ۶۰.۵±۲۱.۵ and ۵۰.۹±۱۱.۲ mg/dL) and total cholesterol (from ۹۷.۵±۱۶.۸ to ۵۹.۶±۸.۵ and ۵۲.۰±۹.۶ mg/dL) levels, while it increased the activity of arylesterase paraoxonase۱ significantly (P<۰.۰۰۱). It also showed a significant (P<۰.۰۰۱) effect on PON۱ gene expression. However, the dose of ۸۰۰ mg/kg was more effective. The results of simulation and molecular dynamics showed that apigenin binds to PON۱ with a high affinity and induces changes in the molecular dynamics parameters. Conclusion: The ۸۰۰ mg/kg of hydroalcoholic extract of T. parthenium can increase the activity of PON۱ and its gene expression. It seems that apigenin as one of the most important antioxidant compounds of this plant can increase the activity of this enzyme by direct binding to PON۱.