Multiprotein Inhibitory Effect of Dietary Polyphenol Rutin from Whole Green Jackfruit Flour Targeting Different Stages of Diabetes Mellitus: Defining a Bio-Computational Stratagem
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plant Material
2.2. Extraction
2.3. Inhibition Assay and Kinetics for AM, AG, and AR Inhibitory Activity
2.4. Assay for Antioxidant Activity
2.5. Analysis of Phenolic Compounds and Ascorbic Acid by HPLC
2.6. Determination of Total Flavonoid Content (TFC) and Total Phenol Content (TPC)
2.7. Separation and Identification of Rutin
2.8. Structural Elucidation
2.9. Multiple Stages of the Human Serum Albumin (HSA) Glycation Inhibition Assay
2.10. Molecular Docking Simulation
2.11. Molecular Dynamics Simulation
2.12. Binding Free Energy Calculations
2.13. Statistical Analysis
3. Results
3.1. Isolation and Identification of Rutin from MJ
3.2. Effect of Isolated Fractions on Multiple Diabetic Enzyme Inhibition
3.3. Enzyme Kinetics of Multiple Diabetic Enzyme Inhibition by Rutin
3.4. Antioxidant Activities of the Isolated Fractions
3.5. Antiglycation Potential of Rutin
3.6. Molecular Docking Simulation
3.7. Molecular Dynamics Simulation
3.8. Binding Free Energy Calculations
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Extracts (Ext.)/Fractions (Fr.) | Enzyme Inhibition IC50 x,y (µg/mL) | Antioxidant Activity EC50 x,z (μg/mL) | ||||
---|---|---|---|---|---|---|
α-Amylase | α-Glucosidase | Aldose Reductase | DPPH | ABTS | Superoxide | |
Chloroform (Ext.) | 43.00 ± 0.86 h | 24.09 ± 0.14 f | 9.00 ± 0.15 d | 35.65 ± 0.57 h | 35.14 ± 1.25 h | 66.25 ± 1.19 i |
Ethyl Acetate (Ext.) | 36.65 ± 0.14 f | 15.00 ±0.88 e | 9.68 ± 1.11 e | 37.05 ± 1.23 i | 32.00 ± 0.00 g | 50.80 ± 0.08 f |
Acetone (Ext.) | 31.00 ± 0.50 e | 14.45 ± 0.23 e | 8.00 ± 0.04 d | 30.66 ± 0.08 f | 28.00 ± 0.94 f | 52.99 ± 0.37 g |
Methanol (Ext.) | 27.95 ± 0.10 c | 10.10 ± 0.20 c | 3.80 ± 1.01 b | 24.55 ± 1.52 d | 21.00 ± 0.96 c | 44.75 ± 1.23 e |
Water (Ext.) | 47.00 ± 0.86 i | 31.15 ± 0.08 g | 10.20 ± 1.41 e | 44.50 ± 0.02 k | 36.65 ± 0.10 h | 57.88 ± 1.33 h |
Petroleum ether (Fr.) | 40.50 ± 1.44 g | 30.50 ± 0.54 g | 8.50 ± 0.30 d | 32.50 ± 0.11 g | 39.15 ± 0.88 i | 57.00 ± 1.00 h |
Ethyl Acetate (Fr.) | 26.15 ± 0.15 c | 09.00 ± 0.10 b | 3.25 ± 0.70 b | 23.50 ± 0.35 d | 19.06 ± 1.74 b | 40.75 ± 0.65 d |
n-butanol (Fr.) | 31.00 ± 0.77 e | 14.50 ± 0.55 e | 6.00 ± 1.01 c | 28.50 ± 0.80 e | 25.00 ± 0.90 e | 46.14 ± 1.26 e |
Cf:Me (22–30) | 28.00 ± 0.34 c | 12.00 ± 1.33 d | 5.50 ± 0.33 c | 27.05 ± 0.12 e | 23.00 ± 0.12 d | 41.50 ± 1.14 d |
Cf:Me (31–36) | 27.88 ± 1.87 c | 10.75 ± 1.02 c | 5.25 ± 0.55 c | 27.10 ± 1.09 e | 22.15 ± 1.73 c | 37.75 ± 1.00 c |
Cf:Me (37–42)—Rutin | 22.00 ± 0.16 a | 07.86 ± 0.33 a | 2.75 ± 0.10 a | 15.00 ± 0.18 a | 10.70 ± 0.47 a | 27.05 ± 1.00 a |
Cf:Me (43–48) | 25.00 ± 0.00 b | 09.05 ± 0.40 b | 6.33 ± 0.21 c | 18.25 ± 1.88 b | 18.55 ± 1.11 b | 30.30 ± 0.04 b |
Cf:Me (49–54) | 28.20 ± 1.33 c | 10.50 ± 0.66 c | 6.00 ± 0.12 c | 25.10 ± 1.01 d | 25.40 ± 0.75 e | 40.06 ± 0.15 d |
Cf:Me (55–60) | 28.13 ± 0.07 c | 09.50 ± 1.10 b | 6.50 ± 0.00 c | 19.20 ± 1.02 c | 20.65 ± 1.66 c | 40.00 ± 0.26 d |
Cf:Me (61–66) | 27.77 ± 1.19 c | 08.80 ± 0.56 b | 5.05 ± 1.00 c | 20.20 ± 1.08 c | 23.35 ± 0.68 d | 35.66 ± 0.14 c |
Cf:Me (67–72) | 28.75 ± 0.55 d | 10.88 ± 0.16 c | 3.90 ± 0.16 b | 34.66 ± 0.09 h | 26.11 ± 0.54 e | 50.00 ± 0.44 f |
Positive control * | 29.00 ± 0.16 d | 11.05 ± 0.23 c | 4.00 ± 0.14 b | 40.00 ± 0.18 j | 31.25 ± 0.02 g | 65.00 ± 0.10 i |
Sl. No. | Name | Ret. Time | Area | Height | Concentration (µg/mg) |
---|---|---|---|---|---|
1 | Ascorbic acid | 4.223 | 294,491 | 35,608 | 17.29 |
2 | Gallic acid | 5.712 | 96,769 | 16,767 | 5.69 |
3 | Catechin | 11.520 | 73,497 | 7891 | 4.32 |
4 | Methyl gallate | 12.436 | 30,776 | 3117 | 1.81 |
5 | Caffeic acid | 14.586 | 21,652 | 2539 | 1.27 |
6 | Syringic acid | 15.033 | 14,842 | 2119 | 0.87 |
7 | Rutin | 18.396 | 11,618 | 1976 | 0.68 |
8 | p-Coumaric acid | 19.068 | 15,034 | 2077 | 0.88 |
9 | Sinapic acid | 19.851 | 38,537 | 6079 | 2.26 |
10 | Ferulic acid | 20.996 | 55,995 | 6370 | 3.29 |
11 | Myricetin | 23.226 | 17,352 | 2102 | 1.02 |
12 | Quercetin | 28.368 | 11,515 | 1267 | 0.68 |
13 | Apigenin | 32.265 | 96,531 | 8183 | 5.67 |
14 | Kaempferol | 34.993 | 107,714 | 10,321 | 6.32 |
Sl. No. | Name of the Compound | α-Glucosidase | α-Amylase | HSA | HAR | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
BA | NB | HB | BA | NB | HB | BA | NB | HB | BA | NB | HB | ||
1 | Ascorbic acid | −5.2 | 3 | 2 | −7.5 | 7 | 2 | −8.1 | 8 | 2 | −6.2 | 5 | 1 |
2 | Gallic acid | −6.4 | 3 | 2 | −8.2 | 8 | 1 | −7.7 | 7 | 2 | −7.8 | 6 | 0 |
3 | Catechin | −6.4 | 2 | 1 | −9.1 | 5 | 2 | −7.1 | 6 | 2 | −8.3 | 8 | 2 |
4 | Methyl gallate | −8.2 | 5 | 4 | −8.1 | 6 | 3 | −6.4 | 9 | 3 | −7.2 | 4 | 3 |
5 | Caffeic acid | −5.9 | 8 | 5 | −6.2 | 5 | 1 | −7.0 | 8 | 4 | −8.2 | 7 | 1 |
6 | Syringic acid | −8.4 | 11 | 6 | −9.1 | 9 | 4 | −8.9 | 10 | 5 | −9.0 | 8 | 4 |
7 | Rutin | −10.5 | 13 | 9 | −10.2 | 10 | 7 | −9.9 | 14 | 6 | −10.2 | 10 | 6 |
8 | p-Coumaric acid | −5.8 | 7 | 5 | −8.3 | 9 | 6 | −9.1 | 7 | 1 | −9.7 | 9 | 3 |
9 | Sinapic acid | −5.6 | 8 | 4 | −7.2 | 7 | 3 | −8.4 | 8 | 2 | −8.2 | 5 | 2 |
10 | Ferulic acid | −8.0 | 6 | 5 | −6.5 | 8 | 3 | −7.1 | 8 | 2 | −6.2 | 8 | 3 |
11 | Myricetin | −9.1 | 5 | 5 | −8.9 | 5 | 2 | −9.2 | 7 | 4 | −7.8 | 6 | 5 |
12 | Apigenin | −8.1 | 6 | 2 | −7.2 | 8 | 2 | −8.1 | 5 | 2 | −8.6 | 5 | 2 |
13 | Kaempferol | −8.5 | 7 | 3 | −8.0 | 7 | 5 | −7.4 | 6 | 3 | −9.1 | 7 | 6 |
14 | Acarbose | −8.2 | 7 | 7 | −8.9 | 5 | 5 | - | - | - | - | - | - |
15 | Amino-guanidine | - | - | - | - | - | - | −6.4 | 2 | 2 | - | - | - |
16 | Quercetin | - | - | - | - | - | - | - | - | - | −7.8 | 8 | 1 |
Protein-Ligand Complexes | Values and Standard Deviations | Types of Binding Free Energies | ||||
---|---|---|---|---|---|---|
Van der Waal’s Energy (kj/mol) | Electrostatic Energy (kj/mol) | Polar Solvation Energy (kj/mol) | SASA Energy (kj/mol) | Binding Energy (kj/mol) | ||
α-glucosidase-rutin | EV | −324.712 | −5.382 | 92.618 | −24.746 | −260.222 |
SD | ±21.580 | ±4.082 | ±13.384 | ±1.441 | ±21.396 | |
α-glucosidase-acarbose | EV | −134.192 | −4.813 | 62.125 | −9.310 | −90.102 |
SD | ±180.341 | ±9.475 | ±58.801 | ±14.719 | ±145.076 | |
α-amylase-rutin | EV | −204.258 | −2.931 | 42.572 | −16.289 | −180.906 |
SD | ±117.430 | ±4.057 | ±39.446 | ±9.495 | ±118.715 | |
α-amylase-acarbose | EV | −130.161 | −2.106 | 39.340 | −9.564 | −87.109 |
SD | ±100.269 | ±22.186 | ±54.310 | ±6.998 | ±61.672 | |
HSA-rutin | EV | −161.503 | −5.499 | 55.663 | −9.513 | −99.851 |
SD | ±41.895 | ±6.908 | ±34.324 | ±3.103 | ±22.691 | |
HSA-aminoguanidine | EV | −150.719 | −5.127 | 47.498 | −7.981 | −81.872 |
SD | ±99.469 | ±10.298 | ±57.619 | ±8.124 | ±79.501 | |
HAR-rutin | EV | −184.694 | −6.705 | 97.407 | −9.678 | −93.670 |
SD | ±81.018 | ±6.141 | ±30.480 | ±7.049 | ±70.236 | |
HAR-quercetin | EV | −171.669 | −3.291 | 81.102 | −8.781 | −85.768 |
SD | ±110.361 | ±34.678 | ±79.539 | ±15.786 | ±92.766 |
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Maradesha, T.; Patil, S.M.; Phanindra, B.; Achar, R.R.; Silina, E.; Stupin, V.; Ramu, R. Multiprotein Inhibitory Effect of Dietary Polyphenol Rutin from Whole Green Jackfruit Flour Targeting Different Stages of Diabetes Mellitus: Defining a Bio-Computational Stratagem. Separations 2022, 9, 262. https://doi.org/10.3390/separations9090262
Maradesha T, Patil SM, Phanindra B, Achar RR, Silina E, Stupin V, Ramu R. Multiprotein Inhibitory Effect of Dietary Polyphenol Rutin from Whole Green Jackfruit Flour Targeting Different Stages of Diabetes Mellitus: Defining a Bio-Computational Stratagem. Separations. 2022; 9(9):262. https://doi.org/10.3390/separations9090262
Chicago/Turabian StyleMaradesha, Tejaswini, Shashank M. Patil, Bhaskar Phanindra, Raghu Ram Achar, Ekaterina Silina, Victor Stupin, and Ramith Ramu. 2022. "Multiprotein Inhibitory Effect of Dietary Polyphenol Rutin from Whole Green Jackfruit Flour Targeting Different Stages of Diabetes Mellitus: Defining a Bio-Computational Stratagem" Separations 9, no. 9: 262. https://doi.org/10.3390/separations9090262