The in vivo study on antioxidant activity of wendan decoction in treating hyperlipidemia: a pharmacokinetic-pharmacodynamic (PK-PD) model

Abstract

Background: Wendan Decoction (WDD) is a six-herb Chinese medicine recipe that was first mentioned in about 652 AD. It is frequently used to treat hyperlipidemic patients’ clinical complaints. According to reports, oxidative stress has a significant role in hyperlipidemia.Purpose: There has not yet been a thorough pharmacokinetic-pharmacodynamic (PK-PD) examination of the clinical efficacy of WDD in the context of hyperlipemia-related oxidative stress. Therefore, the goal of this research is to explore the antioxidant essence of WDD by developing a PK-PD model, ordering to assure its implication in treating hyperlipidemia in medical practice.Methods: The model rats of foodborne hyperlipidemia were established by feeding with high-fat feed, and the lipid-lowering effect of WDD was explored. The plasma drug concentration of rats at different doses were measured by UPL-MS/MS technology, and PK parameters were calculated using Phoenix WinNonlin 8.1 software. The level of lipid peroxide (LPO) in plasma at different time points was measured by enzyme labeling instrument. Finally, the PK-PD model was established by using Phoenix WinNonlin 8.1 software, to explore the lipid-lowering effect of WDD and the relation between the dynamic changes of chemical components and antioxidant effect.Results: The findings suggested that, WDD can reduce the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma, and high-density lipoprotein cholesterol (HDL-C) was related to the dosage. Between the peak drug levels and the WDD’s maximal therapeutic response, there existed a hysteresis. WDD’s effect-concentration curves displayed a counterclockwise delaying loop. Alternatively, among the ten components of WDD, hesperetin, quercetin, naringenin and tangeretin might exert more significant effects in regulating the LPO levels in hyperlipidemic rats.Conclusion: This study can be helpful for other investigators to study the lipid-lowering effect of WDD.