Insulin–Mimetic Dihydroxanthyletin-Type Coumarins from <i>Angelica decursiva</i> with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular Mechanisms
As a traditional medicine, <i>Angelica decursiva</i> has been used for the treatment of many diseases. The goal of this study was to evaluate the potential of four natural major dihydroxanthyletin-type coumarins—(+)-<i>trans</i>-decursidinol, Pd-C-I, Pd-C-II, and Pd-C-III—to...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/2/292 |
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| author | Md Yousof Ali Susoma Jannat Hyun Ah Jung Jae Sue Choi |
| author_facet | Md Yousof Ali Susoma Jannat Hyun Ah Jung Jae Sue Choi |
| author_sort | Md Yousof Ali |
| collection | DOAJ |
| description | As a traditional medicine, <i>Angelica decursiva</i> has been used for the treatment of many diseases. The goal of this study was to evaluate the potential of four natural major dihydroxanthyletin-type coumarins—(+)-<i>trans</i>-decursidinol, Pd-C-I, Pd-C-II, and Pd-C-III—to inhibit the enzymes, protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. In the kinetic study of the PTP1B enzyme’s inhibition, we found that (+)-<i>trans</i>-decursidinol, Pd-C-I, and Pd-C-II led to competitive inhibition, while Pd-C-III displayed mixed-type inhibition. Moreover, (+)-<i>trans</i>-decursidinol exhibited competitive-type, and Pd-C-I and Pd-C-II mixed-type, while Pd-C-III showed non-competitive type inhibition of α-glucosidase. Docking simulations of these coumarins showed negative binding energies and a similar proximity to residues in the PTP1B and α-glucosidase binding pocket, which means they are closely connected and strongly binding with the active enzyme site. In addition, dihydroxanthyletin-type coumarins are up to 40 µM non-toxic in HepG2 cells and have substantially increased glucose uptake and decreased expression of PTP1B in insulin-resistant HepG2 cells. Further, coumarins inhibited ONOO<sup>−</sup>-mediated albumin nitration and scavenged peroxynitrite (ONOO<sup>−</sup>), and reactive oxygen species (ROS). Our overall findings showed that dihydroxanthyletin-type coumarins derived from <i>A</i>. <i>decursiva</i> is used as a dual inhibitor for enzymes, such as PTP1B and α-glucosidase, as well as for insulin susceptibility. |
| first_indexed | 2024-03-09T00:51:44Z |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T00:51:44Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-9f338724bb1141658ea9b83f0df396222023-12-11T17:09:47ZengMDPI AGAntioxidants2076-39212021-02-0110229210.3390/antiox10020292Insulin–Mimetic Dihydroxanthyletin-Type Coumarins from <i>Angelica decursiva</i> with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular MechanismsMd Yousof Ali0Susoma Jannat1Hyun Ah Jung2Jae Sue Choi3Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Food Science and Human Nutrition, Jeonbuk National University, Jeonju 54896, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaAs a traditional medicine, <i>Angelica decursiva</i> has been used for the treatment of many diseases. The goal of this study was to evaluate the potential of four natural major dihydroxanthyletin-type coumarins—(+)-<i>trans</i>-decursidinol, Pd-C-I, Pd-C-II, and Pd-C-III—to inhibit the enzymes, protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. In the kinetic study of the PTP1B enzyme’s inhibition, we found that (+)-<i>trans</i>-decursidinol, Pd-C-I, and Pd-C-II led to competitive inhibition, while Pd-C-III displayed mixed-type inhibition. Moreover, (+)-<i>trans</i>-decursidinol exhibited competitive-type, and Pd-C-I and Pd-C-II mixed-type, while Pd-C-III showed non-competitive type inhibition of α-glucosidase. Docking simulations of these coumarins showed negative binding energies and a similar proximity to residues in the PTP1B and α-glucosidase binding pocket, which means they are closely connected and strongly binding with the active enzyme site. In addition, dihydroxanthyletin-type coumarins are up to 40 µM non-toxic in HepG2 cells and have substantially increased glucose uptake and decreased expression of PTP1B in insulin-resistant HepG2 cells. Further, coumarins inhibited ONOO<sup>−</sup>-mediated albumin nitration and scavenged peroxynitrite (ONOO<sup>−</sup>), and reactive oxygen species (ROS). Our overall findings showed that dihydroxanthyletin-type coumarins derived from <i>A</i>. <i>decursiva</i> is used as a dual inhibitor for enzymes, such as PTP1B and α-glucosidase, as well as for insulin susceptibility.https://www.mdpi.com/2076-3921/10/2/292<i>Angelica decursiva</i>coumarinsPTP1Bα-glucosidaseglucose uptakeantioxidant |
| spellingShingle | Md Yousof Ali Susoma Jannat Hyun Ah Jung Jae Sue Choi Insulin–Mimetic Dihydroxanthyletin-Type Coumarins from <i>Angelica decursiva</i> with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular Mechanisms Antioxidants <i>Angelica decursiva</i> coumarins PTP1B α-glucosidase glucose uptake antioxidant |
| title | Insulin–Mimetic Dihydroxanthyletin-Type Coumarins from <i>Angelica decursiva</i> with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular Mechanisms |
| title_full | Insulin–Mimetic Dihydroxanthyletin-Type Coumarins from <i>Angelica decursiva</i> with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular Mechanisms |
| title_fullStr | Insulin–Mimetic Dihydroxanthyletin-Type Coumarins from <i>Angelica decursiva</i> with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular Mechanisms |
| title_full_unstemmed | Insulin–Mimetic Dihydroxanthyletin-Type Coumarins from <i>Angelica decursiva</i> with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular Mechanisms |
| title_short | Insulin–Mimetic Dihydroxanthyletin-Type Coumarins from <i>Angelica decursiva</i> with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular Mechanisms |
| title_sort | insulin mimetic dihydroxanthyletin type coumarins from i angelica decursiva i with protein tyrosine phosphatase 1b and α glucosidase inhibitory activities and docking studies of their molecular mechanisms |
| topic | <i>Angelica decursiva</i> coumarins PTP1B α-glucosidase glucose uptake antioxidant |
| url | https://www.mdpi.com/2076-3921/10/2/292 |
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