Abstract：
To explore the adjuvant therapy drugs of low-dose metformin, one homogeneous polysaccharide named APS-D1 was purified from Astragalus membranaceus by DEAE-52 cellulose and Sephadex G-100 column chromatography. Its chemical structure was characterized by molecular weight distribution, monosaccharide composition, infrared spectrum, methylation analysis, and NMR. The results revealed that APS-D1 (7.36 kDa) consisted of glucose, galactose, and arabinose (97.51 %:1.56 %:0.93 %). It consisted of →4)-α-D-Glcp-(1→ residue backbone with →3)-β-D-Galp-(1→ residue and terminal-α/β-D-Glcp-(1→ side chains. APS-D1 could significantly improve inflammation (TNF-α, LPS, and IL-10) in vivo. Moreover, APS-D1 improved the curative effect of low-dose metformin without adverse events. APS-D1 combined with low-dose metformin regulated several gut bacteria, in which APS-D1 enriched Staphylococcus lentus to produce l-carnitine (one of 136 metabolites of S. lentus). S. lentus and l-carnitine could improve diabetes, and reduction of S. lentusl-carnitine production impaired diabetes improvement. The combination, S. lentus, and l-carnitine could promote fatty acid oxidation (CPT1) and inhibit gluconeogenesis (PCK and G6Pase). The results indicated that APS-D1 enhanced the curative effect of low-dose metformin to improve diabetes by enriching S. lentus, in which the effect of S. lentus was mediated by l-carnitine. Collectively, these findings support that low-dose metformin supplemented with APS-D1 may be a favorable therapeutic strategy for type 2 diabetes.
摘要：
探讨小剂量二甲双胍的辅助治疗药物,通过DEAE-52纤维素和SephadexG-100柱色谱从黄芪中纯化了一种名为APS-D1的均质多糖。其化学结构由分子量分布表征,单糖组成，红外光谱,甲基化分析，和NMR。结果表明，APS-D1（7.36kDa）由葡萄糖组成，半乳糖,和阿拉伯糖（97.51%：1.56%：0.93%）。它由→4）-α-D-Glcp-（1→残基骨架，→3）-β-D-Galp-（1→残基和末端-α/β-D-Glcp-（1→侧链。APS-D1可以显著改善炎症(TNF-α，LPS,和IL-10）体内。此外，APS-D1可改善小剂量二甲双胍的疗效，且无不良事件发生。APS-D1联合低剂量二甲双胍调节几种肠道细菌，其中APS-D1富集了迟缓葡萄球菌以产生l-肉碱（迟缓葡萄球菌的136种代谢产物之一）。美国Lentus和左旋肉碱可以改善糖尿病，和减少S.lentusl-肉碱产生受损的糖尿病改善。组合，S、Lentus，左旋肉碱可以促进脂肪酸氧化（CPT1）和抑制糖异生（PCK和G6Pase）。结果表明,APS-D1通过富集扁桃体,增强了小剂量二甲双胍改善糖尿病的疗效,其中，L-肉碱介导了Lentus的作用。总的来说，这些发现支持低剂量二甲双胍补充APS-D1可能是2型糖尿病的有利治疗策略.
