The improvement of modified Si-Miao granule on hepatic insulin resistance and glycogen synthesis in type 2 diabetes mellitus involves the inhibition of TNF-α/JNK1/IRS-2 pathway: network pharmacology, molecular docking, and experimental validation.

ABSTRACT:

Background

Modified Si-Miao granule (mSMG), a traditional Chinese medicine, is beneficial for T2DM and insulin resistance (IR), but the underlying mechanism remains unknown.

Methods

Using network pharmacology, we screened the compounds of mSMG and identified its targets and pathway on hepatic IR in T2DM. Using molecular docking, we identified the affinity between the compounds and hub target TNF-α. Then these were verified in KK-Ay mice and HepG2 cells.

Results

50 compounds and 170 targets of mSMG against IR in T2DM were screened, and 9 hub targets such as TNF and MAPK8 were identified. 170 targets were mainly enriched in insulin resistance and TNF pathway, so we speculated that mSMG might act on TNF-α, JNK1 and then regulate insulin signaling to mitigate IR. Experime

SUBMITTER: Cao Z 

PROVIDER: S-EPMC11403785 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature