Apigenin analogs as α-glucosidase inhibitors: Molecular docking, biochemical, enzyme kinetic, and an in vivo mouse model study.

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Honghui Liu, Yanxu Wei, Yan Wang, Qiu Zhao, Lan Liu, Hong Ding, Yuntian Hong
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Abstract

Due to the high incidence of diabetes and its associated complications, diabetes is widely recognized as a serious global health problem. In diabetes treatment strategies, targeting α-glucosidase, a key carbohydratehydrolyzing enzyme, has emerged as a highly regarded approach. To develop novel α-glucosidase inhibitors, we successfully synthesized a series of apigenin analogs, collectively referred to as H1-H27 compounds and examined their inhibitory effects on α-glucosidase activity. H7 showed a remarkable inhibitory effect, surpassing that of the standard drug acarbose. Further analysis revealed that H7, H10, and H24 act as non-competitive inhibitors of α- glucosidase. In vivo experiments using a type 2 diabetes mouse model demonstrated the diverse therapeutic potential of H7; it effectively lowered blood sugar levels, improved glucose tolerance, and corrected lipid metabolism. In addition, H7 showed hepatoprotective effects, highlighting its ability to improve liver function. H7 also positively influenced the gut microbiota composition in diabetic mice, increasing diversity and richness. These results highlight the promising therapeutic effects of apigenin analogs, such as H7, for treating type 2 diabetes and show how they could provide numerous benefits, including effective inhibition of α-glucosidase, improved glucose control, correction of lipid metabolism, hepatoprotection, and modulation of the intestinal microbiota.

作为α-葡萄糖苷酶抑制剂的芹菜素类似物:分子对接、生物化学、酶动力学和体内小鼠模型研究。
由于糖尿病及其相关并发症的高发病率,糖尿病已被公认为一个严重的全球健康问题。在糖尿病治疗策略中,针对α-葡萄糖苷酶(一种关键的碳水化合物水解酶)的治疗方法备受推崇。为了开发新型α-葡萄糖苷酶抑制剂,我们成功合成了一系列芹菜素类似物,统称为H1-H27化合物,并考察了它们对α-葡萄糖苷酶活性的抑制作用。H7 的抑制效果显著,超过了标准药物阿卡波糖。进一步的分析表明,H7、H10 和 H24 是α-葡萄糖苷酶的非竞争性抑制剂。使用 2 型糖尿病小鼠模型进行的体内实验证明了 H7 的多种治疗潜力;它能有效降低血糖水平、改善葡萄糖耐量并纠正脂质代谢。此外,H7 还具有保护肝脏的作用,突显了其改善肝功能的能力。H7 还对糖尿病小鼠的肠道微生物群组成产生了积极影响,增加了多样性和丰富度。这些结果凸显了芹菜素类似物(如 H7)在治疗 2 型糖尿病方面的良好疗效,并说明了芹菜素类似物可带来的诸多益处,包括有效抑制α-葡萄糖苷酶、改善血糖控制、纠正脂质代谢、保护肝脏以及调节肠道微生物群。
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来源期刊
Bioorganic Chemistry
Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
9.70
自引率
3.90%
发文量
679
审稿时长
31 days
期刊介绍: Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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