Aldose reductase inhibitory and antiglycation properties of phytoconstituents of Cichorium intybus: Potential therapeutic role in diabetic retinopathy.

Autor: Ahmad S; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail- 2440, Saudi Arabia. Electronic address: ahmadsaheem@gmail.com., Ahmad MFA; Department of Biosciences, Integral University, Lucknow 226026, India., Alouffi S; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail- 2440, Saudi Arabia. Electronic address: s.alouffi@uoh.edu.sa., Khan S; Department of Basic Dental and Medical Sciences, College of Dentistry, University of Hail, Saudi Arabia. Electronic address: sf.khan@uoh.edu.sa., Khan M; Department of Biology, College of Science, University of Hail- 2440, Saudi Arabia. Electronic address: mk.khan@uoh.edu.sa., Khan MWA; Department of Chemistry, College of Science, University of Hail- 2440, Saudi Arabia. Electronic address: mw.khan@uoh.edu.sa., Prakash C; University Centre for Research and Development, Chandigarh University, Mohali, Punjab, India. Electronic address: chander.prakash@cumail.in., Ahmad N; Department of Computer Science and Information System, College of Applied Sciences, AlMaarefa University, P.O. Box 71666, Riyadh 13713, Saudi Arabia. Electronic address: nahmad@um.edu.sa., Ansari IA; Department of Biosciences, Integral University, Lucknow 226026, India. Electronic address: ahmadirfan.amu@gmail.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Oct; Vol. 277 (Pt 1), pp. 133816. Date of Electronic Publication: 2024 Jul 11.
DOI: 10.1016/j.ijbiomac.2024.133816
Abstrakt: Diabetic vascular complication including diabetic retinopathy is a major morbidity in Saudia Arabia. The polyol pathway aka aldose reductase (AR) pathway has gained significant association with diabetic retinopathy with regard to chronically enhanced glucose metabolism. Considerable research has been put forth to develop more effective therapeutic strategies to overcome the overwhelming challenges of vascular complications associated with diabetes. In this regard, constituents of Cichorium intybus can offer strong AR inhibitory potential because of their strong antidiabetic properties. Therefore, aim of this study was to investigate the AR inhibitory as well as antiglycation potential of C. intybus extract/compounds. The preliminary in vitro results showed that methanolic extract of C. intybus could significantly inhibit AR enzyme and advanced glycation end product formation. Eventually, based on previous studies and reviews, we selected one hundred fifteen C. intybus root constituents and screened them through Lipinski's rule of five and ADMET analysis. Later, after molecular docking analysis of eight compounds, five best were selected for molecular dynamics simulation to deduce their binding affinity with the AR enzyme. Finally, three out of five compounds were further tested in vitro for their AR inhibitory potential and antiglycation properties. Enzyme assay and kinetic studies showed that all the three tested compounds were having potent AR inhibitory properties, although to a lesser extent than ellagic acid and tolrestat. Similarly, kaempferol showed strong antiglycation property equivalent to ellagic acid, but greater than aminoguanidine. Intriguingly, significant reduction in sorbitol accumulation in RBCs by the tested compounds substantiated strong AR inhibition by these compounds. Moreover, decrease in sorbitol accumulation under high glucose environment also signifies the potential application of these compounds in diabetic retinopathy and other vascular complications. Thus, in sum, the in silico and in vitro studies combinedly showed that C. intybus root is a treasure for therapeutic compounds and can be explored further for drug development against diabetic retinopathy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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