Trigonella foenum-graecum L. ameliorates metabolism-associated fatty liver disease in type 2 diabetic mice: a multi-omics mechanism analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Trigonella foenum-graecum L. (HLB), a widely recognized traditional Chinese medicine, has been historically used for the treatment of diabetes mellitus and its complications. However, the efficacy and mechanism of HLB in the treatment of type 2 diabetes mellitus (T2DM) combined with metabolic-associated fatty liver disease (MAFLD) remain poorly understood.

AIM OF THE STUDY: To investigate the therapeutic effects of HLB on T2DM combined with MAFLD in mice and elucidate its underlying mechanisms.

MATERIALS AND

METHODS

The indices of glucose and lipid metabolism, along with oxidative stress markers, were measured using commercially available assay kits. Histopathological analyses of liver and colon tissues were conducted. Additionally, the mRNA expression levels of genes related to fatty acid metabolism, inflammatory factors, and intestinal tight junction proteins were quantified using reverse transcription polymerase chain reaction (RT-PCR). Microbiome, metabolomic, and transcriptomic analyses were employed to evaluate gut microbiota composition, metabolic profiles, and liver differential genes, respectively.

RESULTS

After a 4-week treatment period, HLB effectively ameliorated abnormalities of glucose-lipid metabolism, hepatic oxidative stress, and inflammatory responses. Furthermore, HLB modulated hepatic function and intestinal damage. Through comprehensive multi-omics analysis, the observed improvements were attributed to the remodeling of the gut microbiota and its metabolic alterations, including an increased abundance of beneficial bacteria, regulation of bile acid metabolism.

CONCLUSIONS

These findings not only provide a theoretical foundation for the broader application of HLB in traditional Chinese medicine but also offer novel insights into the potential pharmacological mechanisms underlying HLB's efficacy in T2DM and MAFLD treatment.