Investigation of the effects of Terminalia chebula seed hydroalcoholic extract on Paraoxonase۱ enzyme activity in rats

Background and aims: Paraoxonase ۱ (PON۱) is related to high-density lipoprotein (HDL) in serum and protects against low-density lipoprotein (LDL) oxidation. This study aimed to investigate the effects of Terminalia chebula on PON۱ in hyperlipidemic rats and the molecular docking effects of some compounds of this medical plant on PON۱ activity. Methods: Overall, ۴۰ male rats (۲۰۰–۲۵۰ gr) were randomly divided into four groups, including the control group, the hyperlipid group, the hyperlipid group receiving ۴۰۰ mg/kg of the hydroalcoholic extract of T. chebula seeds, and the hyperlipid group receiving ۸۰۰ mg/kg of the hydroalcoholic extract of T. chebula seeds. The PON۱ arylesterase activity in serum and the PON۱ gene expression in the liver tissue underwent investigation. Then, the molecular docking effects of its compounds were studied on PON۱ through in-silico studies using the AutoDock software (version ۴.۲.۰). Results: T. chebula decreased (P<۰.۰۰۱) the serum triglycerides from ۱۰۵.۸۸±۱۰.۱۵ mg/dL in the hyperlipidemic group to ۶۶.۸۸±۱۴.۹۰ and ۷۴.۲۵±۹.۵۱ mg/dL in hyperlipidemic groups receiving ۴۰۰ and ۸۰۰ mg/kg of the hydroalcoholic extract of T. chebula seeds, respectively. In addition, the PON۱ serum aryl esterase activity increased from ۲۰۲.۱۲±۶۰۵۸ in hyperlipidemic rats to ۲۲۴.۳۴±۵۸.۷۴ (P=۰.۸۳) and ۲۳۵.۸۰±۳۷.۰۵ (P=۰.۶) in hyperlipidemic groups receiving ۴۰۰ mg/kg and ۸۰۰ mg/kg of the hydroalcoholic extract of T. chebula seeds, respectively. It also demonstrated a significant effect on PON۱ gene expression (P<۰.۰۰۱). In addition, the in-silico and docking results revealed that the main antioxidant compounds of T. chebula, such as catechin, kaempferol, and quercetin, could bind to the PON۱ enzyme directly and influence the enzyme activity. Conclusion: T. chebula increased PON۱ activity and PON۱ gene expression. However, among the plant’s compounds, catechin, kaempferol, and quercetin played the most substantial role in the PON۱ activity. It seems that these compounds can be useful as co-treatments in hyperlipidemia therapies.