Metabolic Mechanism of Qizhi Capsule for Treating Hyperlipoidemia Based on Chinmedomics Strategy

Abstract

To elucidate the active ingredients, and mechanism of action of Qizhi Capsules (QZC), a traditional Chinese patent medicine for the treatment of hyperlipidemia (HP). A high-fat diet-induced HP rat model was used to evaluate the therapeutic effect of QZC. Then, we integrated metabolomics, serum pharmacochemistry, network pharmacology, and molecular docking strategies for investigation. Results showed that QZC significantly alleviated the physiological symptoms of HP, with remarkable restoration of the levels of cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein. It can also reverse pathological changes in liver function to healthy levels. Besides, metabolomic analysis identified 24 metabolites as biomarkers which are highly related to HP. All the markers were settled back to normal with the intervention of QZC. Seventy-seven compounds originated from QZC were found in blood; 17 of them were highly related to the trajectory change of biomarkers of HP. These compounds were the potential effective constituents related to its clinical efficacy, such as Emodin et al. These ingredients regulated the biomarker farnesol to target Farnesoid X receptor (FXR) involved in cholesterol and triglyceride metabolism with HP. QZC possesses a favorable efficacy on HP; the core mechanism may activate FXR by modulating farnesol with multiple components, thereby reversing the metabolism of HP.