Synergistic mechanism of salt-processed Anemarrhenae Rhizoma on type 2 diabetes via gut microbiota and metabolic regulation.

BACKGROUND: Salt processing, a traditional Chinese medicine (TCM) processing technique, entails stir-frying herbs with salt water. Anemarrhenae Rhizoma (AR) is an example of a TCM herb that enhances renal function after salt processing. AR and salt-processed AR (SAR) exhibit potent hypoglycemic effects, particularly pronounced in salt-processed AR. However, the therapeutic mechanisms of both in type 2 diabetes mellitus (T2DM) require further investigation.

PURPOSE: This work is intended to unravel the synergistic mechanism involved in SAR-based management of T2DM.

METHODS: This study explored the anti-T2DM mechanisms of AR and SAR using network pharmacology. Their effects were confirmed in insulin-resistant HepG2 cells. Molecular docking, Western blot, and qRT-PCR validated key targets and pathways. A high-fat diet plus STZ-induced T2DM rat model assessed in vivo efficacy, and urinary metabolomics combined with 16S rRNA sequencing was employed to elucidate the regulatory mechanisms of SAR.

RESULTS: Network pharmacology screened 16 active ingredients and 62 core targets, and molecular docking confirmed their excellent target-binding ability. In vitro experiments demonstrated that AR and SAR could regulate the insulin signaling pathway through INSR and MTOR. Additionally, they modulated 20 differential metabolites and effectively restored gut microbiota dysbiosis in T2DM rats.

CONCLUSION: Integrated metabolomics and microbiology analyses clarified the potentiating effect of SAR against T2DM. SAR ameliorated urinary metabolism and gut microbiota balance, offering novel mechanistic references for its clinical use.