The water extract of Potentilla discolor Bunge (PDW) ameliorates high-sugar diet-induced type II diabetes model in Drosophila melanogaster via JAK/STAT signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Potentilla discolor Bunge (PD) is a member of the Rosaceae family. It has been traditionally used in folk medicine for the treatment of diabetes. Additionally, people in folk also eat fresh and tender PD stems as vegetables or brew them as tea. AIM OF THE STUDY: The aim of this study was to explore the antidiabetic effects and underlying mechanisms of the water extract of Potentilla discolor (PDW) in a fruit fly model of high-sugar diet-induced type 2 diabetes. MATERIALS AND METHODS: The antidiabetic efficacy of PDW was evaluated in a fruit fly model of diabetes induced by a high-sugar diet (HSD). Various physiological parameters were tested to evaluate the anti-diabetic effect of PDW. Gene expression levels related to insulin signaling pathways, glucose metabolism, lipid metabolism, and JAK/STAT signaling pathways were primarily analyzed using RT-qPCR to investigate the therapeutic mechanisms. RESULTS: In this study, we found that the water extract of Potentilla discolor (PDW) can ameliorate type II diabetes phenotypes induced by the HSD in fruit flies. These phenotypes include growth rate, body size, hyperglycemia, glycogen metabolism, fat storage, and intestinal microflora homeostasis. PDW also improved the body size of s6k and rheb knockdown flies, suggesting its potential to activate the downstream insulin pathway and alleviate insulin resistance. Furthermore, we demonstrated that PDW reduced the expression of two target genes of the JAK/STAT signaling pathway, namely the insulin antagonist Impl2 and insulin receptor inhibitor Socs36E, which act as regulators inhibiting the activation of the insulin signaling pathway. CONCLUSIONS: This study provides evidence for the anti-diabetic activity of PDW and suggests that its underlying mechanism may involve the improvement of insulin resistance by inhibiting the JAK/STAT signaling pathway.