1Comprehensive multi-omics analysis reveals the mechanism of loganin from Corni Fructus in improving insulin resistance in mice

Corni Fructus (CF) has great potential as a food product in the treatment of T2DM (thirst-quenching). As the main active ingredient of CF, loganin (LOG) possesses multiple pharmacological propertiesincluding hypoglycemic, hypolipidemic, anti-inflammatory and antibacterial. In this study, we firstly verified the efficacy of LOG in improving the disordered glycolipid metabolism and liver damages in a murine insulin resistance (IR) model, and then determined the ameliorative effect of LOG on IR-HepG2 cell model. To clarify the mechanism of LOG on IR, a series of differentially expressed metabolites (DEM) and genes (DEG) were screened out through non-targeted metabolomics and transcriptomics techniques. In addition, integrative metabolomics and transcriptomics analyses revealed a few key pathways (foxO signaling pathway, glycine serine and threonine metabolism, glutamatergic synapse, cocaine addiction, amphetamine addiction, and valine leucine and isoleucine biosynthesis), important DEM (l-Glutamate), and DEGs (Sgk2, Grin3b, Acadsb, Grik1) were reversely regulated by LOG as compared with the IR model. It is hypothesized that LOG may exert the anti-IR effect via finely tuning amino acid metabolism. Taken together, our data may shine light on the screening of new intervention targets and developing of new LOG-related agents for IR treatment. [Display omitted] •Loganin ameliorates disturbed glucolipid metabolism and hepatic impairment in insulin-resistant mice.•Loganin increased PA-induced cell viability as well as restored disturbed glycolipid metabolism in IR-HepG2.•Possible pathways of loganin intervention in insulin resistance by combined transcriptomics and metabolomics analysis.•Loganin may modulate insulin resistance by interfering with amino acid metabolism.