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.