翻白草水提物通过 JAK/STAT 信号通路改善黑腹果蝇的高糖饮食诱导的 II 型糖尿病模型。

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

机构信息

School of Pharmaceutical Science and Technology, Tianjin University, 300072, Tianjin, China.

出版信息

J Ethnopharmacol. 2023 Nov 15;316:116760. doi: 10.1016/j.jep.2023.116760. Epub 2023 Jun 8.

DOI:10.1016/j.jep.2023.116760

PMID:37301307

Abstract

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.

摘要

民族药理学相关性

翻白草（PD）是蔷薇科的一员。它在民间医学中一直被用于治疗糖尿病。此外，民间的人们还会食用新鲜嫩的 PD 茎作为蔬菜，或用它们泡茶。

研究目的

本研究旨在探讨翻白草水提物（PDW）在高糖饮食诱导的果蝇 2 型糖尿病模型中的降血糖作用及其作用机制。

材料与方法

采用高糖饮食（HSD）诱导的果蝇糖尿病模型评价 PDW 的降血糖作用。测试了各种生理参数，以评估 PDW 的抗糖尿病作用。主要采用 RT-qPCR 分析与胰岛素信号通路、葡萄糖代谢、脂代谢和 JAK/STAT 信号通路相关的基因表达水平，以探讨治疗机制。

结果

本研究发现，翻白草水提物（PDW）可改善高糖饮食诱导的果蝇 2 型糖尿病表型。这些表型包括生长速度、体型、高血糖、糖原代谢、脂肪储存和肠道微生物区系稳态。PDW 还改善了 s6k 和 rheb 敲低果蝇的体型，表明其可能激活下游胰岛素通路并减轻胰岛素抵抗。此外，我们证明 PDW 降低了 JAK/STAT 信号通路的两个靶基因的表达，即胰岛素拮抗剂 Impl2 和胰岛素受体抑制剂 Socs36E，它们作为抑制胰岛素信号通路激活的调节剂。