Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking Study
This present work is designed to evaluate the anti-diabetic potential of 22 ginsenosides via the inhibition against rat lens aldose reductase (RLAR), and human recombinant aldose reductase (HRAR), using <sub>DL</sub>-glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenosi...
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MDPI AG
2022-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/7/2134 |
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| author | Md Yousof Ali Sumera Zaib Susoma Jannat Imtiaz Khan M. Mizanur Rahman Seong Kyu Park Mun Seog Chang |
| author_facet | Md Yousof Ali Sumera Zaib Susoma Jannat Imtiaz Khan M. Mizanur Rahman Seong Kyu Park Mun Seog Chang |
| author_sort | Md Yousof Ali |
| collection | DOAJ |
| description | This present work is designed to evaluate the anti-diabetic potential of 22 ginsenosides via the inhibition against rat lens aldose reductase (RLAR), and human recombinant aldose reductase (HRAR), using <sub>DL</sub>-glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenoside Rh2, (20<i>S</i>) ginsenoside Rg3, (20<i>R</i>) ginsenoside Rg3, and ginsenoside Rh1 inhibited RLAR significantly, with IC<sub>50</sub> values of 0.67, 1.25, 4.28, and 7.28 µM, respectively. Moreover, protopanaxadiol, protopanaxatriol, compound K, and ginsenoside Rh1 were potent inhibitors of HRAR, with IC<sub>50</sub> values of 0.36, 1.43, 2.23, and 4.66 µM, respectively. The relationship of structure–activity exposed that the existence of hydroxyl groups, linkages, and their stereo-structure, as well as the sugar moieties of the ginsenoside skeleton, represented a significant role in the inhibition of HRAR and RLAR. Additional, various modes of ginsenoside inhibition and molecular docking simulation indicated negative binding energies. It was also indicated that it has a strong capacity and high affinity to bind the active sites of enzymes. Further, active ginsenosides suppressed sorbitol accumulation in rat lenses under high-glucose conditions, demonstrating their potential to prevent sorbitol accumulation ex vivo. The findings of the present study suggest the potential of ginsenoside derivatives for use in the development of therapeutic or preventive agents for diabetic complications. |
| first_indexed | 2024-03-09T11:36:48Z |
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| id | doaj.art-35d60e1aa36b421d90d4dfca5da45779 |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:36:48Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-35d60e1aa36b421d90d4dfca5da457792023-11-30T23:40:01ZengMDPI AGMolecules1420-30492022-03-01277213410.3390/molecules27072134Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking StudyMd Yousof Ali0Sumera Zaib1Susoma Jannat2Imtiaz Khan3M. Mizanur Rahman4Seong Kyu Park5Mun Seog Chang6Department 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, Faculty of Life Sciences, University of Central Punjab, Lahore 54590, PakistanDepartment of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB T2N 1N4, CanadaDepartment of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UKDepartment of Biotechnology and Genetic Engineering, Faculty of Biological Science, Islamic University, Kushtia 7003, BangladeshDepartment of Prescriptionology, College of Korean Medicine, Kyung Hee University, 26 Kyunghee dae-ro, Dongdaemun-gu, Seoul 02447, KoreaDepartment of Prescriptionology, College of Korean Medicine, Kyung Hee University, 26 Kyunghee dae-ro, Dongdaemun-gu, Seoul 02447, KoreaThis present work is designed to evaluate the anti-diabetic potential of 22 ginsenosides via the inhibition against rat lens aldose reductase (RLAR), and human recombinant aldose reductase (HRAR), using <sub>DL</sub>-glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenoside Rh2, (20<i>S</i>) ginsenoside Rg3, (20<i>R</i>) ginsenoside Rg3, and ginsenoside Rh1 inhibited RLAR significantly, with IC<sub>50</sub> values of 0.67, 1.25, 4.28, and 7.28 µM, respectively. Moreover, protopanaxadiol, protopanaxatriol, compound K, and ginsenoside Rh1 were potent inhibitors of HRAR, with IC<sub>50</sub> values of 0.36, 1.43, 2.23, and 4.66 µM, respectively. The relationship of structure–activity exposed that the existence of hydroxyl groups, linkages, and their stereo-structure, as well as the sugar moieties of the ginsenoside skeleton, represented a significant role in the inhibition of HRAR and RLAR. Additional, various modes of ginsenoside inhibition and molecular docking simulation indicated negative binding energies. It was also indicated that it has a strong capacity and high affinity to bind the active sites of enzymes. Further, active ginsenosides suppressed sorbitol accumulation in rat lenses under high-glucose conditions, demonstrating their potential to prevent sorbitol accumulation ex vivo. The findings of the present study suggest the potential of ginsenoside derivatives for use in the development of therapeutic or preventive agents for diabetic complications.https://www.mdpi.com/1420-3049/27/7/2134ginsenosidesdiabetic complicationaldose reductaseenzyme kineticsmolecular dockingsorbitol accumulation |
| spellingShingle | Md Yousof Ali Sumera Zaib Susoma Jannat Imtiaz Khan M. Mizanur Rahman Seong Kyu Park Mun Seog Chang Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking Study Molecules ginsenosides diabetic complication aldose reductase enzyme kinetics molecular docking sorbitol accumulation |
| title | Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking Study |
| title_full | Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking Study |
| title_fullStr | Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking Study |
| title_full_unstemmed | Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking Study |
| title_short | Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking Study |
| title_sort | inhibition of aldose reductase by ginsenoside derivatives via a specific structure activity relationship with kinetics mechanism and molecular docking study |
| topic | ginsenosides diabetic complication aldose reductase enzyme kinetics molecular docking sorbitol accumulation |
| url | https://www.mdpi.com/1420-3049/27/7/2134 |
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