Citrus Flavanone Narirutin, In Vitro and In Silico Mechanistic Antidiabetic Potential
Abstract
:1. Introduction
2. Results and Discussion
2.1. Molecular Docking
2.1.1. PTP1B
2.1.2. DPP4
2.1.3. FFAR1
2.1.4. Alpha-Amylase
2.1.5. PPARγ
2.1.6. Alpha-Glucosidase
2.1.7. Aldose Reductase
2.1.8. Glycogen Phosphorylase
2.2. In Vitro Assays
2.2.1. Alpha-Amylase Inhibitory Effect
2.2.2. Alpha-Glucosidase Inhibitory Effect
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. Molecular Docking
3.2.1. Preparation of the Ligand
3.2.2. Preparation of the Receptors
3.2.3. Simulation
3.3. Narirutin In-Vitro Inhibition Potential on Digestive Enzymes
3.3.1. Alpha-Amylase Inhibition Assay
3.3.2. Alpha-Glucosidase Inhibitory Assay
3.4. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Receptor | Affinity (kcal/mol) | Active Site Described in Literature | Interaction Confirmed with the Active Site | H-Bonds |
---|---|---|---|---|
PTP1B | −8.5 | Trp179, Pro180, Asp181 [26], His214, Ser216, Ala217, Gly218, Ile219, Gly220, and Arg221 [27,28] and the active site on Cys 215 (catalytic loop) | Yes | Arg221, Arg24, Ser216 |
DPP4 | −10.4 | DPP4 active site (α/β-hydrolase domain) is identified by the residues from 39 to 51 and from 501 to 706 [29,30]. | Yes | Tyr662, Ser209, Ser630, Arg125, His740, Trp629, |
FFAR1 | −8.3 | Active site includes Arg183, Arg258 and Tyr2240 [31]. Binding pocket is on Glu172, Arg183, Ser187, Tyr240, Asn241, Asn244, Arg258 and Tyr91 [32,33]. | Yes | Tyr44 |
Alpha amylase | −9.9 | Active site:Asp197, Glu233 and Asp300 and other important AA: Arg337, Arg195, Asn298, Phe265, Phe295, His201, Ala307, Gly306, Trp203, Trp284, Trp59, Tyr62, Trp58, His299 and His101 [34,35,36,37]. | Yes | Gly306, Asp197, Gln63, Trp69, Lys352, Asp352 |
PPAR gamma | - | PPARγ ligand-binding domain: Ser289, His323, Tyr473, and His449 [38]. | No | |
Alpha glucosidase | −8.7 | The amino acids involved in the α-Glucosidase activity are Asp404, Asp518, Arg600, Asp616, and His674 Trp376, Ile441, Trp516, Met519, Trp613, and Phe649 Leu405, Trp481, Asp645, and Arg672 [39,40]. | Yes | Asp616, Ala284, Arg281, Asp282, Ser523 |
Aldose reductase | −9.3 | The active site is located in the barrel core clearly seen in the 3D structure [41] | Yes | Val47, Gln49, Lys21, Ser32 |
Glycogen phosphorylase | −8.3 | Active site on amino acids 280–288 (The 280’s loop) [42,43]. | Yes | Asp283, Glu382, leu384 |
Alpha-Amylase In Vitro IC50 (mg/mL) | Alpha-Glucosidase In Vitro IC50 (mg/mL) | Alpha-Amylase In Silico Affinity (kcal/mol) | Alpha-Glucosidase In Silico Affinity (kcal/mol) | |
---|---|---|---|---|
Narirutin | 0.0066 | 0.00091 | −9.9 | −8.7 |
Acarbose | 1.012 | 0.00035 | −8.1 | −8.4 |
Receptor | PID | Resolution (Å) | Classification |
---|---|---|---|
Protein tyrosine phosphatase 1B (PTP1B) | 1c83 | 1.80 | Hydrolase |
Glycogen phosphorylase (GP) | 1l5q | 2.25 | Transferase |
Free fatty acid receptor 1 (FFAR1) | 4phu | 2.33 | Hydrolase |
Peroxisome proliferator-activated receptor gamma (PPAR gamma) | 5ycp | 2.00 | Transcription |
Alpha-amylase (AAM) | 1smd | 1.60 | Hydrolase |
Alpha-glucosidase (AGL) | 5nn5 | 2.00 | Hydrolase |
Aldose reductase (AR) | 2hv5 | 1.59 | Oxidoreductase |
dipeptidyl peptidase IV (DPP4) | 2p8s | 2.20 | Hydrolase |
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Qurtam, A.A.; Mechchate, H.; Es-safi, I.; Al-zharani, M.; Nasr, F.A.; Noman, O.M.; Aleissa, M.; Imtara, H.; Aleissa, A.M.; Bouhrim, M.; et al. Citrus Flavanone Narirutin, In Vitro and In Silico Mechanistic Antidiabetic Potential. Pharmaceutics 2021, 13, 1818. https://doi.org/10.3390/pharmaceutics13111818
Qurtam AA, Mechchate H, Es-safi I, Al-zharani M, Nasr FA, Noman OM, Aleissa M, Imtara H, Aleissa AM, Bouhrim M, et al. Citrus Flavanone Narirutin, In Vitro and In Silico Mechanistic Antidiabetic Potential. Pharmaceutics. 2021; 13(11):1818. https://doi.org/10.3390/pharmaceutics13111818
Chicago/Turabian StyleQurtam, Ashraf Ahmed, Hamza Mechchate, Imane Es-safi, Mohammed Al-zharani, Fahd A. Nasr, Omar M. Noman, Mohammed Aleissa, Hamada Imtara, Abdulmalik M. Aleissa, Mohamed Bouhrim, and et al. 2021. "Citrus Flavanone Narirutin, In Vitro and In Silico Mechanistic Antidiabetic Potential" Pharmaceutics 13, no. 11: 1818. https://doi.org/10.3390/pharmaceutics13111818
APA StyleQurtam, A. A., Mechchate, H., Es-safi, I., Al-zharani, M., Nasr, F. A., Noman, O. M., Aleissa, M., Imtara, H., Aleissa, A. M., Bouhrim, M., & Alqahtani, A. S. (2021). Citrus Flavanone Narirutin, In Vitro and In Silico Mechanistic Antidiabetic Potential. Pharmaceutics, 13(11), 1818. https://doi.org/10.3390/pharmaceutics13111818