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 -glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenoside Rh2, (20 ) ginsenoside...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2022-03, Vol.27 (7), p.2134
Main Authors: Ali, Md Yousof, Zaib, Sumera, Jannat, Susoma, Khan, Imtiaz, Rahman, M Mizanur, Park, Seong Kyu, Chang, Mun Seog
Format: Article
Language:English
Subjects:
Aldehyde Reductase
aldose reductase
Animals
diabetic complication
enzyme kinetics
ginsenosides
Ginsenosides - chemistry
Ginsenosides - pharmacology
Kinetics
molecular docking
Molecular Docking Simulation
Rats
Sorbitol
sorbitol accumulation
Structure-Activity Relationship
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Summary: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 -glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenoside Rh2, (20 ) ginsenoside Rg3, (20 ) ginsenoside Rg3, and ginsenoside Rh1 inhibited RLAR significantly, with IC 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 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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27072134