Preclinical Pharmacokinetics and Pharmacodynamics of Coptidis Preparation in Combination with Lovastatin in High-Fat Diet-Induced Hyperlipidemic Rats

Abstract

Lovastatin is a standard therapy for dyslipidemia. Alternatively, some ethnomedicines, such as Coptidis preparation, have been used for the treatment of dyslipidemia. Statins and complementary and alternative medicines may possess individual mechanisms of action against dyslipidemia. We hypothesize that the combination of Coptidis preparation and lovastatin may have synergistic effects for the treatment of dyslipidemia. To investigate this hypothesis, we developed a validated ultra-high-performance liquid chromatography-tandem mass spectrometry method to monitor lovastatin and its metabolites for pharmacokinetic studies in rats. This study was divided into four groups: lovastatin (10 mg/kg, p.o.) alone and lovastatin (10 mg/kg, p.o.) + Coptidis preparation (0.3, 1, or 3 g/kg, p.o.) for five consecutive days. In pharmacodynamic studies, a high-fat diet (HFD) was used to induce dyslipidemia in experimental rat models. The HFD rats were divided into four groups: treatment with HFD, HFD + lovastatin (100 mg/kg, p.o.), HFD + Coptidis preparation (1 g/kg, p.o.), and HFD + lovastatin (50 mg/kg, p.o.) + Coptidis preparation (1 g/kg, p.o.) for 28 consecutive days. The pharmacokinetic results demonstrated that Coptidis preparation significantly augmented the conversion of lovastatin into its main metabolite lovastatin acid in vivo. The pharmacodynamic results revealed that the Coptidis preparation and half-dose lovastatin group reduced the body weight, liver weight, and visceral fat in HFD rats. These findings provide constructive preclinical pharmacokinetic and pharmacodynamic applications of Coptidis preparation on the benefit of hyperlipidemia.

Morphometric analysis of fatty liver with the treatment of ginseng root extract

“…This study highlights the effect of a high-fat diet on gross morphology as well as the histology of the liver. The high-fat diet was prepared with fats from cow, cheese, and butter, contrary to a high-fat diet prepared by peng in 2021 20 . A high-fat diet changes liver weight, size, and color, also demonstrated by marques in 2021 21 .…”

Natural Products for Cancer Therapy: A Review of Their Mechanism of Actions and Toxicity in the Past Decade

“…Over the years, C. rhizoma has been used to treat several illnesses including diabetes, eczema, diarrhoea, jaundice and high fever. Its many pharmacological properties such as antiviral, antibacterial, antifungal, antidiabetic, antioxidant, anti-inflammatory, and anticancer effects, make it one of the most versatile therapeutic natural products [50][51][52]. C. rhizoma constitutes about 120 chemical components ranging from alkaloids, volatile oils, organic acids, lignans, and flavones [53,54].…”