Optimization of the proportions of advantageous components in the hypolipidemic "bioequivalent substance system" of Jiang-Zhi-Ning and its mechanism of action.

ABSTRACT

CONTEXT Jiang-Zhi-Ning (JZN), a traditional Chinese medicinal formula, is used to treat hyperlipidemia in clinics. OBJECTIVE: To screen the hypolipidemic "bioequivalent substance system (BSS)" of JZN and elucidate the potential hypolipidemic mechanism. MATERIALS AND METHODS: In vitro, the TG content in HepG2 cells was determined after the intervention of the combination of advantageous components (CAC) by uniform design. In vivo, hyperlipidemia models were established by Triton WR-1339 (400 mg/kg; i.p.) in male ICR mice, and corresponding treatments were administered via oral administration once. The mice were divided into 12 groups (n = 5) control, hyperlipidemic model, simvastatin (positive control, 20 mg/kg), gradient doses of JZN granules (2, 4 and 8 g/kg) and the hypolipidemic effective extraction (HEE) of JZN (120, 240 and 480 mg/kg) and CAC groups (20, 40 and 160 mg/kg). Serum TC, TG, LDL-C and HDL-C were performed after 24 h. Transcriptomics and qRT-PCR technology were used to explore the mechanism of the "BSS" of JZN. RESULTS: In vitro, the ratio of CAC was determined. CAC could reduce the TG content in HepG2 cells (77.21%). Compared with the model group, the high dose of CAC could markedly decrease the levels of TC (61.86%), TG (105.54%) and LDL-C (39.38%) and increase the level of HDL-C (232.67%). CAC was proved to be the "BSS". Transcriptomics and qRT-PCR analysis revealed CAC regulated non-alcoholic fatty liver disease, bile secretion, PPAR and adipocytokine signalling pathway. DISCUSSION AND CONCLUSIONS: These findings provided new feasible ideas and methods for the elucidation of the pharmacodynamic material basis.