Exploration of Diosmin to control diabitis and its complications-an in vitro and in silico approach

Author(s):  
Kushagra Dubey ◽  
Raghvendra Dubey ◽  
Revathi Gupta ◽  
Arun Gupta

Background: Diosmin is a flavonoid obtained from the citrus fruits of the plants. Diosmin has blood lipid lowering activities, antioxidant activity, enhances venous tone and microcirculation, protects capillaries, mainly by reducing systemic oxidative stress. Objective: The present study demonstrates the potential of Diosmin against the enzymes aldose reductase, α-glucosidase, and α-amylase involved in diabetes and its complications by in vitro evaluation and reverse molecular docking studies. Method: The assay of aldose reductase was performed by using NADPH as starting material and DL-Glyceraldehyde as a substrate. DNS method was used for alpha amylase inhibition and in alpha glucosidase inhibitory activity p-nitrophenyl glucopyranoside (pNPG) was used as substrate. The reverse molecular docking studies was performed by using Molegro software (MVD) with grid resolution of 30 Å. Result: Diosmin shows potent inhibitory effect against aldose reductase (IC50:333.88±0.04 µg/mL), α-glucosidase (IC50:410.3±0.01 µg/mL) and α-amylase (IC50: 404.22±0.02 µg/mL) respectively. The standard drugs shows moderate inhibitory activity for enzymes. The MolDock Score of Diosmin was -224.127 against aldose reductase, -168.17 against α-glucosidase and -176.013 against α-amylase respectively, which was much higher than standard drugs. Conclusion: From the result it was concluded that diosmin was a potentially inhibitor of aldose reductase, alpha amylase and alpha glucosidase enzymes then the standard drugs and it will be helpful in the management of diabetes and its complications. This will also be benevolent to decrease the socio economical burden on the middle class family of the society.

2015 ◽  
Vol 6 (8) ◽  
pp. 2693-2700 ◽  
Author(s):  
Aditya Arvindekar ◽  
Tanaji More ◽  
Pavan V. Payghan ◽  
Kirti Laddha ◽  
Nanda Ghoshal ◽  
...  

The 1,8-dihydroxyanthraquinones from the culinary and medicinally important plant Rheum emodi exert anti-hyperglycemic potential but notably different α-glucosidase actions as established by in vitro, in vivo, kinetics and molecular docking studies.


2020 ◽  
Author(s):  
Mohsinul Mulk Bacha ◽  
Humaira Nadeem ◽  
Shafiq Ur Rehman ◽  
Sadia Sarwar ◽  
Aqeel Imran ◽  
...  

Abstract In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2.


2019 ◽  
Vol 28 (6) ◽  
pp. 873-883 ◽  
Author(s):  
Momin Khan ◽  
Ghulam Ahad ◽  
Abdul Manaf ◽  
Reshma Naz ◽  
Syed Roohul Hussain ◽  
...  

Molecules ◽  
2017 ◽  
Vol 22 (9) ◽  
pp. 1555 ◽  
Author(s):  
Zipeng Gong ◽  
Yaping Peng ◽  
Jie Qiu ◽  
Anbai Cao ◽  
Guangcheng Wang ◽  
...  

2018 ◽  
Vol 80 ◽  
pp. 129-144 ◽  
Author(s):  
Bilquees Bano ◽  
Kanwal ◽  
Khalid Mohammed Khan ◽  
Arif Lodhi ◽  
Uzma Salar ◽  
...  

2019 ◽  
Vol 24 (4) ◽  
pp. 1149-1164
Author(s):  
Sinem Yakarsonmez ◽  
Ozkan Danis ◽  
Ozal Mutlu ◽  
Murat Topuzogullari ◽  
Emrah Sariyer ◽  
...  

2020 ◽  
Author(s):  
Mohsinul Mulk Bacha ◽  
Humaira Nadeem ◽  
Sumera Zaib ◽  
Sadia Sarwar ◽  
Aqeel Imran ◽  
...  

Abstract In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2. The binding site analysis of potent compounds revealed similar interactions as were found by cognate ligands within the active sites of enzymes.


Author(s):  
Gejalakshmi S. ◽  
Harikrishnan N. ◽  
Anas S. Mohameid

Background: Diabetes mellitus is a metabolic condition characterized by elevated blood glucose levels in the bloodstream. It occurs due to the inadequate amount of insulin secreted in the body or resistance of insulin receptors. Objective: In the present study, for its effect on alpha-amylase and alpha-glucosidase enzymes, Oroxylum indicuma flavone glycoside was assessed using in-vitro assays by removing the respective enzymes from whole wheat and barley in conjunction with in-silico analysis. Method: in-vitro alpha amylase inhibitory activity and in-vitro alpha glucosidase inhibitory activity was performed using acarbose as a standard drug. The molecular docking study was performed using Schrodinger (Maestro V 11.5) software. The parameters glide score, Lipinski rule for drug likeliness, bioactive scoring and ADME properties were assessed in the docking study. In addition, baicalein's antioxidant function was assessed using DPPH assay, nitric oxide scavenging activity. The cytotoxicity of Oroxylum indicumwas evaluated using the Brine shrimp lethality assay. Results: The alpha-amylase assay performed showed IC50 value of 48.40 µg/ml for Oroxylum indicumwhereas alpha-glucosidase assay showed an IC50 value of 16.03 µg/ml. Oroxylum indicumshows the glide score of-5.565 with 5EOF and glide score of -5.339 with 5NN8 in the molecular docking study. The highest percentage of DPPH radical scavenging activity and nitrous oxide scavenging activity were found to be.27% at160 µg/ml and 50.02% at the concentrations of 160 µg/ml respectively. Conclusion: Based on further in vivo and clinical trials, Oroxylum indicummay be used for the management of hyperglycaemia.


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