Fufang Zhenzhu Tiaozhi (
FTZ) capsules have been prescribed for treating
glucose and
lipid metabolism disorders such as
type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unknown. In this study, network pharmacology and experimental verification were combined to investigate the mechanisms of
FTZ in treating T2DM. A total of 176 active ingredients and 1169 corresponding targets were screened using biological databases. 598 potential targets of T2DM were retrieved from GeneCards, PharmGKB, OMIM, Drugbank, and TTD. The Venn diagram was employed to identify the 194 intersection targets, which were employed to construct the "Herb-Compound-Target" interacting networks. These common targets were also used to prepare a
protein-
protein interaction (PPI) network to uncover potential targets. The four core targets were docked to their corresponding targets for binding analysis. Additionally, the top-ranked poses of ingredients and the positive compounds from each
protein were evaluated for stability using molecular dynamics. Our results suggest that core active ingredients such as
kaempferol,
luteolin, and
baicalein have high binding affinity and stability with AKT1,
PTGS2 (also known as COX-2), DPP4, and PAPRG. GO and KEGG analyses indicated that the treatment T2DM by
FTZ might be related to different pathway like AMPK and EGFR pathways. The experimental validation results proved that
kaempferol,
luteolin, and
baicalein could significantly inhibit the activity of DPP4 and COX-2,
kaempferol and
luteolin were also able to activate AKT and AMPK signaling pathway. This study further validated previous findings and enhanced our understanding of the potential effects of
FTZ on T2DM.Communicated by Ramaswamy H. Sarma.