[Jiangzhi Quban Recipe improves type 2 diabetes mellitus complicated with hyperlipidemia by multi-target regulation of the inflammation-metabolism network: network pharmacology analysis and clinical validation].

OBJECTIVES

To explore the therapeutic mechanism of Jiangzhi Quban Recipe (JZQBR) for type 2 diabetes mellitus (T2DM) complicated with hyperlipidemia and validate its clinical efficacy and safety.

METHODS

The active components and disease targets of JZQBR were screened using TCMSP and GeneCards databases, followed by protein-protein interaction analysis and GO and KEGG enrichment analyses. In the animal experiments, ApoE-/- mice were randomized into blank control, model, simvastatin treatment, and low- and high-dose JZQBR groups. In the latter 4 groups, the mice were fed a high-fat diet for 24 weeks with corresponding treatments from Weeks 9 to 24. The changes in body weight, blood glucose, lipids, liver pathology, and inflammatory cytokine expressions of the mice were examined. In the clinical study, 72 T2DM patients with hyperlipidemia were randomized equally into control group for treatment with metformin plus empagliflozin and JZQBR group with additional JZQBR for 12 consecutive weeks.

RESULTS

Network pharmacology identified 65 potential targets, with quercetin, kaempferol, and luteolin as the core components and IL-6, IL-1β, and TNF‑α as the key targets. The targets were enriched mainly in the pathways involving inflammatory responses and diabetic complications. In the ApoE-/- mouse models, JZQBR treatment dose-dependently improved body weight, blood glucose, and blood lipid profiles, and high-dose JZQBR produced a stronger effect than simvastatin for improving hepatic steatosis and significantly reduced inflammatory cytokine levels. In the clinical trial, 29 patients in JZQBR group and 31 in the control group completed the trial. The patients in JZQBR group showed significant improvements in body weight, FBG, TG, HbA1c, and liver enzymes with significantly lower fasting blood glucose level than the control group. The total effective rates were comparable between the two groups.

CONCLUSIONS

JZQBR improves T2DM complicated with hyperlipidemia possibly by multi-target regulation of the inflammation-metabolism network.