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

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

  • Bioorg Chem. 2024 Dec:153:107956. doi: 10.1016/j.bioorg.2024.107956.
Honghui Liu 1,  Yanxu Wei 2,  Yan Wang 3,  Qiu Zhao 4,  Lan Liu 5,  Hong Ding 6,  Yuntian Hong 7
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases, Hubei Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China.
  • 2 Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases, Hubei Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China.
  • 3 Department of Hematology, Zhongda Hospital, School of Medicine, Southeast University, Institute of Hematology, Nanjing 210009, China.
  • 4 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases, Hubei Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China. Electronic address: qiuzhao@whu.edu.cn.
  • 5 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases, Hubei Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China. Electronic address: lliugi@whu.edu.cn.
  • 6 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China. Electronic address: 2021103060005@whu.edu.cn.
  • 7 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases, Hubei Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China. Electronic address: 3130101818@zju.edu.cn.
PMID: 39561436 DOI: 10.1016/j.bioorg.2024.107956
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.

Keywords

Apigenin analogs; Carbohydratehydrolyzing α-glucosidase; Type 2 diabetes.

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