About 4% of the world’s population has type 2 diabetes mellitus (T2DM), and the available hypoglycemic drugs for treating diabetes have some side effects. Therefore, research on the extraction of hypoglycemic components from plants has gradually become popular. This study aimed to investigate the hypoglycemic effects of polyphenol-rich Rosa roxburghii Tratt extract (RP) isolated from Rosa roxburghii Tratt fruit and of four constituents (IRP 1–4 ) isolated from RP on db/db mice. The results indicated that the oral administration of RP and IRP 1–4 could markedly decrease the food intake, water intake, fasting blood glucose (FBG), and serum insulin levels in the db/db mice. Glucose intolerance, insulin resistance, and oxidative stress were ameliorated in the RP and IRP 1–4 groups. Histopathological observation revealed that RP and IRP 1–4 could effectively protect the liver fat against damage and dysfunction. RP and IRP 1–4 also increased the hepatic and muscle glycogen contents by increasing the phosphorylation and reducing the expression of glycogen synthase kinase 3β (GSK3β). The activities of glucokinase (GCK), phosphoenolpyruvate carboxylase (PEPCK), and glucose-6-phosphatase (G6PC) and their respective mRNA expression levels in the liver of db/db mice were simultaneously increased and decreased in the intervention groups. RP and IRP 1–4 significantly increased the expression of phosphatidylinositol 3-kinase (P13K) and the phosphorylation of protein kinase B (AKT). These results indicate that RP and IRP 1–4 exhibit good hypoglycemic effects by activating the P13K/AKT signaling pathway and regulating the expression of FOXO1 and p-GSK3β proteins, controlling hepatic gluconeogenesis and improving hepatic glycogen storage insulin resistance. Therefore, RP and IRP 1–4 could be utilized as the hypoglycemic functional component to alleviate the symptoms of T2DM.

Rosa roxburghii fruit is an underutilized functional food abundant in polyphenols. Polyphenols have been proved to have antidiabetic effects. This study investigates the effects of Rosa roxburghii fruit polyphenols extract (RPE) on plasma metabolites and gut microbiota composition in streptozotocin (STZ)- and high-fat diet- induced type 2 diabetes using metabolomics and 16S rRNA gene sequencing. The induced diabetic mice were fed with 400 mg/kg body weight RPE for 8 weeks. RPE demonstrated hypoglycemic, hypolipidemic, and anti-inflammatory effects. Colonic oxidative stress biomarkers were also lowered by RPE. Besides, RPE decreased plasma ceramides and tyrosine levels and increased carnitine and phosphatidylinositols levels, indicating improved insulin resistance, lipid metabolism, and immune response. Furthermore, RPE decreased abundances of Lachnospiraceae and Rikenellaceae and increased abundances of Erysipelotrichaceae and Faecalibaculum. Metabolic function prediction of the gut microbiota by PICRUSt demonstrated that RPE downregulated the phosphotransferase system. Taken together, these findings demonstrated that RPE has the potential to prevent type 2 diabetes by regulating the plasma metabolites and gut microbes.

Hydroxy-α-sanshool (HAS), hydroxy-β-sanshool (HBS), hydroxy-γ-sanshool (HRS), and γ-sanshool (RS) are the key components from the Zanthoxylum genus, processing a range of pharmacological activities. The present study investigated the protective capacities of four sanshools on a dextran sulfate sodium (DSS)-induced model of ulcerative colitis (UC). The results showed that sanshool administration alleviated the colitis symptoms by reducing body weight loss and disease activity index (DAI) score, increasing the colon length, and improving colonic injury and the change in immune organ weight. Furthermore, sanshools enhanced the antioxidant enzyme activities, and RS exhibited the lowest effect on the improvement in total antioxidative capacity (T-AOC) and antioxidant abilities compared to the other three sanshools. The p65 nuclear factor κB (p65 NFκB) signaling pathway was inhibited to prevent hyperactivation and decreased the production of inflammatory factors. The gut barrier function in DSS-induced mice was restored by increasing goblet cell number and levels of tight junction proteins (zonula occludens-1, occludin, and claudin-1), and the levels of protein in HAS and HRS groups were higher than that in the HBS group, significantly. The analysis of gut microbiota suggested that sanshool administration significantly boosted the abundance of Lachnospiraceae, Muribaculaceae, Oscillospiraceae, and Alistipes and reduced the level of Buchnera in colitis mice. Collectively, the sanshool treatment could ameliorate colitis by resisting colon injury and regulating intestinal barrier dysfunction and gut microbiota dysbiosis; meanwhile, HRS and HAS have better improvement effects.