Yang Bing, Xiong Zhiwei, Lin Meng, Yang Yanjun, Chen Yaping, Zeng Jingqi, Jia Xiaobin, Feng Liang
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China.
Int J Biol Macromol. 2023 Apr 15;234:123767. doi: 10.1016/j.ijbiomac.2023.123767. Epub 2023 Feb 20.
Type 1 diabetes (T1D) is a serious health problem that needs to be addressed worldwide. Astragalus polysaccharides (APS), the main chemical components of Astragali Radix, have anti-diabetic activity. As most plant polysaccharides are difficult to digest and absorb, we hypothesised that APS exert hypoglycaemic effects through the gut. This study intends to investigate the modulation of T1D associated with gut microbiota by neutral fraction of Astragalus polysaccharides (APS-1). T1D mice were induced with streptozotocin and then treated with APS-1 for 8 weeks. Fasting blood glucose levels were decreased and the insulin levels were increased in T1D mice. The results demonstrated that APS-1 improved gut barrier function by regulating ZO-1, Occludin and Claudin-1 expression, and reconstructed gut microbiota by increasing the relative abundance of Muribaculum, Lactobacillus and Faecalibaculum. In addition, APS-1 significantly increased the levels of acetic acid, propionic acid, butyric acid and inhibited the expression of pro-inflammatory factors IL-6 and TNF-α in T1D mice. Further exploration revealed that APS-1 alleviation of T1D may be associated with short-chain fatty acids (SCFAs)-producing bacteria, and that SCFAs binds to GPRs and HDACs proteins and modulate the inflammatory responses. In conclusion, the study supports the potential of APS-1 as a therapeutic agent for T1D.
1型糖尿病（T1D）是一个严重的健康问题，需要在全球范围内加以解决。黄芪多糖（APS）是黄芪的主要化学成分，具有抗糖尿病活性。由于大多数植物多糖难以消化吸收，我们推测APS通过肠道发挥降血糖作用。本研究旨在探讨黄芪多糖中性组分（APS-1）对与肠道微生物群相关的T1D的调节作用。用链脲佐菌素诱导T1D小鼠，然后用APS-1治疗8周。T1D小鼠的空腹血糖水平降低，胰岛素水平升高。结果表明，APS-1通过调节紧密连接蛋白1（ZO-1）、闭合蛋白（Occludin）和紧密连接蛋白1（Claudin-1）的表达改善肠道屏障功能，并通过增加穆里杆菌属（Muribaculum）、乳杆菌属（Lactobacillus）和粪杆菌属（Faecalibaculum）的相对丰度重建肠道微生物群。此外，APS-1显著提高了T1D小鼠中乙酸、丙酸、丁酸的水平，并抑制了促炎因子白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达。进一步探索发现，APS-1对T1D的缓解作用可能与产生短链脂肪酸（SCFAs）的细菌有关，并且SCFAs与G蛋白偶联受体（GPRs）和组蛋白去乙酰化酶（HDACs）蛋白结合并调节炎症反应。总之，该研究支持了APS-1作为T1D治疗药物的潜力。
