Synthesis and α-Glycosidase Inhibitory Activity of Three Ascorbic Acid Glycosides

Abstract

2-O-(β-D-Glucopyranosyl)-L-ascorbic acid, a natural β-glycoside with ascorbic acid moiety present in Lycium barbarum, and its two analogues were chemically synthesized. Their inhibitory effect on yeast α-glucosidase and α-amylase were investigated with commercially available acarbose as positive control. The biological assays demonstrated the distinct inhibitory effect of these compounds on α-glucosidase activity and weak inhibitory activity against pancreatic α-amylase. The kinetic study indicated that these compounds were competitive inhibitors. These results imply that these three β-glycosides have the potential to be developed as α-glucosidase inhibitors. Keywords 2-O-(β-D-glucopyranosyl)-L-ascorbic acid; analogue; synthesis; α-glucosidase; α-amylase; inhibitor 糖尿病是一种代谢紊乱疾病, 已成为三大严重威胁 人类健康的慢性疾病之一 [1]. 根据 2014 年国际糖尿病联 合会的统计, 全世界糖尿病患者超过 4.5 亿人, 其中 II 型糖尿病(非胰岛素依耐性糖尿病)占比超过 90% [2]. 在 治疗 II 型糖尿病的药物中, α-葡萄糖苷酶抑制剂如阿卡 波糖等疗效非常显著, 但是阿卡波糖也常常会引起腹 鸣、腹胀、腹痛等副作用 [3] , 因此寻求更高效安全低副 作用的抗糖尿病药物一直是药物研究的重要目标 [4]. 枸杞果实是一种传统的中药, 在中国和一些亚洲国 家已经当作保健品食用了两千多年. 研究发现, 枸杞具 有丰富的药理活性, 如抗氧化、降血压、降血糖等效 果 [5]. 2-O-β-D-葡萄糖基-L-抗坏血酸(AA-2βG)是一种天 然的抗坏血酸衍生物, 最早由日本学者 Toyada-ono 从宁 夏枸杞中分离得到 [6] , AA-2βG 在体内只能被小肠中的 β-糖苷酶水解, 具有缓释抗坏血酸的作用, 能达到持续清 除自由基和抗氧化的效果 [7] , 还能抑制 Hela 细胞增殖生 长 [8]. 根据 AA-2βG 分子的结构特点, 我们推测 AA-2βG 有可能会与食物中糖类化合物在结合 α-糖苷酶时产生 竞争, 起到抑制血糖急剧升高的作用. 为了证实这个推 测, 我们合成了 AA-2βG 及其两种类似物 2-O-β-D-半乳 糖基-L-抗坏血酸(AA-2βGal)和 3-O-β-D-葡萄糖基-L-抗 坏血酸(AA-3βG), 并研究了它们在体外对 α-糖苷酶的 影响.

A comprehensive review of goji berry processing and utilization

“…In 2017, Ma et al. ( 2017 ) upgraded the preparation method of AA‐2βG. The synthetic pathway of AA‐2βG is shown in Scheme 1 .…”

2-O-β-d-Glucopyranosyl l-Ascorbic Acid, a Stable Form of Vitamin C, Is Widespread in Crop Plants

“…We suggested that AA-2βG had been lost from domestic apples ( Malus x domestica ) through centuries of selective breeding (it is also possible that the high AA-2βG content of crab apple fruit is due to a mutation preventing the degradation of AA-2βG in the fruit back to ascorbate and glucose). AA-2βG has similar stability to AA-2αG, a synthetic AAG used in many cosmetic products for its superior stability to AA. − AA-2βG has been shown to act as pro-vitamin C when ingested by rats and to have various valuable physiological functions, including the potential to act as an alpha-glucosidase inhibitor and modulating gut microbiota to palliate colitis in mice. − …”