Astragalus mongholicus polysaccharides alleviate insulin resistance through modulation of PI3K/AKT, TLR4/NF-kB signaling pathway and microbiota in rats with Type 2 Diabetes Mellitus

IF 3.3 3区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Journal of Traditional and Complementary Medicine Pub Date : 2025-05-01 DOI:10.1016/j.jtcme.2024.05.007

Haisheng Yuan , Guoquan Xu , Jingran Liu , Yan Yan , Shimin Zhao , Fujuan Cai , Xiuling Yu , Yuzhen Wang , Minhui Li

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Abstract

Background and aim

Astragali Radix has been widely used in traditional Chinese medicine to treat diabetes and a variety of other diseases. This study aims to evaluate the alleviating effects and mechanisms of Astragalus mongholicus Polysaccharide (mAPS) against diet combined with streptozotocin (STZ)-induced Type 2 Diabetes Mellitus (T2DM).

Experimental procedure

T2DM rats were orally administrated either with 200 mg/kg mAPS or 300 mg/kg Metformin (MET) once daily for four weeks. Body weight and Fasting Blood Glucose (FBG) were detected every 6 days. Serum fasting insulin (FINS) was measured by ELISA and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated accordingly. Histological change was studied by Hematoxylin and eosin (HE) staining. 16S rDNA sequencing was used to detect the changes in gut microbiota.

Results and conclusion

Oral administration of mAPS significantly decreased body weight, FBG, and HOMA-IR in T2DM rats (p＜0.05). Moreover, HE staining showed that mAPS could alleviate histological distortion in the liver and pancreas. Treatment with mAPS elevated the hepatic levels of phosphatidylinositol-3 kinase (PI3K), phospho-protein kinase B (AKT), and glucose transporter type 4 (GLUT4), while reducing phospho-nuclear factor kappa-B (NF-κB), Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) (p＜0.05). Furthermore, mAPS supplementation could reverse the ratio of Firmicutes/Bacteroidetes (F/B) and reduce the abundance of Clostridia and Proteobacteria (p＜0.05). These results indicate that mAPS have the potential to enhance insulin sensitivity in diabetic rats by modifying gut microbiota and controlling the hepatic glycolipid metabolism and inflammation.

Abstract Image

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黄芪多糖通过调节 PI3K/AKT、TLR4/NF-kB 信号通路和微生物群减轻 2 型糖尿病大鼠的胰岛素抵抗

背景与目的黄芪在中药中被广泛用于治疗糖尿病和其他多种疾病。本研究旨在探讨黄芪多糖（mAPS）对日粮联合链脲佐菌素（STZ）诱导的2型糖尿病（T2DM）的缓解作用及其机制。实验方法2dm大鼠分别口服map 200 mg/kg或Metformin 300 mg/kg，每日1次，连续4周。每6 d检测一次体重和空腹血糖（FBG）。ELISA法测定血清空腹胰岛素（FINS），计算胰岛素抵抗稳态模型评估（HOMA-IR）。苏木精和伊红（HE）染色观察组织学变化。采用16S rDNA测序检测肠道菌群的变化。结果与结论口服mAPS可显著降低T2DM大鼠体重、FBG、HOMA-IR （p<0.05）。此外，HE染色显示mAPS能减轻肝脏和胰腺的组织学扭曲。map可提高肝脏磷脂酰肌醇-3激酶（PI3K）、磷酸化蛋白激酶B （AKT）和葡萄糖转运蛋白4型（GLUT4）水平，降低磷酸化核因子κB （NF-κB）、toll样受体4 （TLR4）、肿瘤坏死因子-α (TNF-α)、白细胞介素-6 （IL-6）和白细胞介素-1β (IL-1β)水平（p<0.05）。此外，添加mAPS可以逆转厚壁菌门/拟杆菌门（F/B）的比例，降低梭菌门和变形杆菌门的丰度（p<0.05）。这些结果表明，mAPS可能通过改变肠道菌群和控制肝脏糖脂代谢和炎症来增强糖尿病大鼠的胰岛素敏感性。

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来源期刊

Journal of Traditional and Complementary Medicine Medicine-Complementary and Alternative Medicine

CiteScore

9.30

自引率

6.70%

发文量

审稿时长

66 days

期刊介绍： eJTCM is committed to publish research providing the biological and clinical grounds for using Traditional and Complementary Medical treatments as well as studies that demonstrate the pathophysiological and molecular/biochemical bases supporting the effectiveness of such treatments. Review articles are by invitation only. eJTCM is receiving an increasing amount of submission, and we need to adopt more stringent criteria to select the articles that can be considered for peer review. Note that eJTCM is striving to increase the quality and medical relevance of the publications.