α-Glucosidase Inhibition Mechanism and Anti-Hyperglycemic Effects of Flavonoids from Astragali Radix and Their Mixture Effects
<b>Background</b>: Inhibition of intestinal α-glucosidase is a key strategy for controlling postprandial hyperglycemia in diabetes. Astragali Radix (AR), a traditional medicinal and dietary herb widely consumed in China, is rich in flavonoids that are believed to exhibit hypoglycemic pro...
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MDPI AG
2025-05-01
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| author | Xing Han Pengpu Wang Jing Zhang Yang Lv Zhigao Zhao Fengxian Zhang Mingying Shang Guangxue Liu Xuan Wang Shaoqing Cai Feng Xu |
| author_facet | Xing Han Pengpu Wang Jing Zhang Yang Lv Zhigao Zhao Fengxian Zhang Mingying Shang Guangxue Liu Xuan Wang Shaoqing Cai Feng Xu |
| author_sort | Xing Han |
| collection | DOAJ |
| description | <b>Background</b>: Inhibition of intestinal α-glucosidase is a key strategy for controlling postprandial hyperglycemia in diabetes. Astragali Radix (AR), a traditional medicinal and dietary herb widely consumed in China, is rich in flavonoids that are believed to exhibit hypoglycemic properties. <b>Methods</b>: A total of 29 AR-related flavonoids, including both original constituents and metabolites, were screened for <i>α</i>-glucosidase inhibitory activity using in vitro enzymatic assays. Mechanistic investigations were conducted through enzyme kinetics, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), and molecular docking. The in vivo hypoglycemic effects were assessed using a postprandial hyperglycemic mouse model. Additionally, potential mixture effects of flavonoid combinations were evaluated. <b>Results</b>: Of the 29 flavonoids, 16 demonstrated significant α-glucosidase inhibitory activity, with five (<b>C3</b>, <b>C17</b>, <b>C19</b>, <b>C28</b>, and <b>C29</b>) identified as novel inhibitors. Structure–activity relationship (SAR) analysis revealed that hydroxylation, particularly at the C-3 position, enhanced activity, while glycosylation and methoxylation reduced it. Mechanistic studies demonstrated that these compounds bind to distinct amino acid residues within the active site of α-glucosidase, inducing conformational changes and exerting different types of inhibition, leading to varying inhibitory mechanisms. Additionally, 15 compounds reduced postprandial blood glucose levels, with <b>C3</b>, <b>C16</b>, <b>C17</b>, <b>C19</b>, and <b>C28</b> confirmed as novel in vivo inhibitors. Notably, two compositions of flavonoids combined at their individually ineffective concentrations exhibited significant inhibitory effects. <b>Conclusions</b>: This study provides a comprehensive evaluation of AR-related flavonoids as α-glucosidase inhibitors and offers valuable insights for the development of highly effective, low-toxicity, flavonoid-based, antidiabetic therapeutics and functional foods. |
| format | Article |
| id | doaj-art-0ece28b353944f458ae7817c930622dc |
| institution | OA Journals |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-0ece28b353944f458ae7817c930622dc2025-08-20T01:56:41ZengMDPI AGPharmaceuticals1424-82472025-05-0118574410.3390/ph18050744α-Glucosidase Inhibition Mechanism and Anti-Hyperglycemic Effects of Flavonoids from Astragali Radix and Their Mixture EffectsXing Han0Pengpu Wang1Jing Zhang2Yang Lv3Zhigao Zhao4Fengxian Zhang5Mingying Shang6Guangxue Liu7Xuan Wang8Shaoqing Cai9Feng Xu10State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaDepartment of Chemical Biology, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, China<b>Background</b>: Inhibition of intestinal α-glucosidase is a key strategy for controlling postprandial hyperglycemia in diabetes. Astragali Radix (AR), a traditional medicinal and dietary herb widely consumed in China, is rich in flavonoids that are believed to exhibit hypoglycemic properties. <b>Methods</b>: A total of 29 AR-related flavonoids, including both original constituents and metabolites, were screened for <i>α</i>-glucosidase inhibitory activity using in vitro enzymatic assays. Mechanistic investigations were conducted through enzyme kinetics, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), and molecular docking. The in vivo hypoglycemic effects were assessed using a postprandial hyperglycemic mouse model. Additionally, potential mixture effects of flavonoid combinations were evaluated. <b>Results</b>: Of the 29 flavonoids, 16 demonstrated significant α-glucosidase inhibitory activity, with five (<b>C3</b>, <b>C17</b>, <b>C19</b>, <b>C28</b>, and <b>C29</b>) identified as novel inhibitors. Structure–activity relationship (SAR) analysis revealed that hydroxylation, particularly at the C-3 position, enhanced activity, while glycosylation and methoxylation reduced it. Mechanistic studies demonstrated that these compounds bind to distinct amino acid residues within the active site of α-glucosidase, inducing conformational changes and exerting different types of inhibition, leading to varying inhibitory mechanisms. Additionally, 15 compounds reduced postprandial blood glucose levels, with <b>C3</b>, <b>C16</b>, <b>C17</b>, <b>C19</b>, and <b>C28</b> confirmed as novel in vivo inhibitors. Notably, two compositions of flavonoids combined at their individually ineffective concentrations exhibited significant inhibitory effects. <b>Conclusions</b>: This study provides a comprehensive evaluation of AR-related flavonoids as α-glucosidase inhibitors and offers valuable insights for the development of highly effective, low-toxicity, flavonoid-based, antidiabetic therapeutics and functional foods.https://www.mdpi.com/1424-8247/18/5/744astragali radixflavonoidsα-glucosidaseinhibitory mechanismpostprandial hyperglycemiamixture effect |
| spellingShingle | Xing Han Pengpu Wang Jing Zhang Yang Lv Zhigao Zhao Fengxian Zhang Mingying Shang Guangxue Liu Xuan Wang Shaoqing Cai Feng Xu α-Glucosidase Inhibition Mechanism and Anti-Hyperglycemic Effects of Flavonoids from Astragali Radix and Their Mixture Effects Pharmaceuticals astragali radix flavonoids α-glucosidase inhibitory mechanism postprandial hyperglycemia mixture effect |
| title | α-Glucosidase Inhibition Mechanism and Anti-Hyperglycemic Effects of Flavonoids from Astragali Radix and Their Mixture Effects |
| title_full | α-Glucosidase Inhibition Mechanism and Anti-Hyperglycemic Effects of Flavonoids from Astragali Radix and Their Mixture Effects |
| title_fullStr | α-Glucosidase Inhibition Mechanism and Anti-Hyperglycemic Effects of Flavonoids from Astragali Radix and Their Mixture Effects |
| title_full_unstemmed | α-Glucosidase Inhibition Mechanism and Anti-Hyperglycemic Effects of Flavonoids from Astragali Radix and Their Mixture Effects |
| title_short | α-Glucosidase Inhibition Mechanism and Anti-Hyperglycemic Effects of Flavonoids from Astragali Radix and Their Mixture Effects |
| title_sort | α glucosidase inhibition mechanism and anti hyperglycemic effects of flavonoids from astragali radix and their mixture effects |
| topic | astragali radix flavonoids α-glucosidase inhibitory mechanism postprandial hyperglycemia mixture effect |
| url | https://www.mdpi.com/1424-8247/18/5/744 |
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