Unlocking the anti-diabetic potential of Pyracantha fortuneana fruit: A natural remedy to combat type 2 diabetes in SD rats

Pyracantha fortuneana fruit (PF), a traditional edible-medicinal resource, holds promising potential for functional food and nutraceutical applications. In this study, we evaluated the preventive effects of PF on T2DM in Sprague-Dawley (SD) rats using a high-fat and high-sugar diet combined with streptozotocin (STZ)-induced diabetes model. Forty male SD rats were randomly divided into four groups: normal control (NC), model control (MC), low-dose PF (PF-L, 450 mg/kg/d), and high-dose PF (PF-H, 900 mg/kg/d). The rats were administered PF or vehicle for six weeks before STZ injection, followed by assessments of body weight, glucose tolerance, insulin sensitivity, and serum lipid profiles. UHPLC-MS/MS analysis identified 15 PF-derived compounds in the bloodstream, including flavonoids and phenolic acids. 16S rDNA sequencing revealed that PF pre-intervention restored gut microbiota balance by reducing pathogenic bacteria (e.g., Prevotella 9) and increasing beneficial taxa (e.g., Blautia). Serum metabolomics demonstrated PF’s regulatory effects on 269 metabolites, particularly in glycerophospholipid metabolism and bile acid pathways. Correlation analysis linked six key PF components to improved metabolic and microbial profiles, suggesting a multi-target mechanism for its anti-diabetic effects. These findings highlight PF as a promising natural intervention for T2DM, with potential applications in functional foods or nutraceuticals. These findings highlight PF as a valuable natural resource for developing functional foods or nutraceuticals to manage T2DM, supporting its further industrial exploitation.