Structure-activity relationships and the underlying mechanism of α-amylase inhibition by hyperoside and quercetin: Multi-spectroscopy and molecular docking analyses

Shen, Heyu; Wang, Jun; Ao, Jingfang; Hou, Yujie; Xi, Meihua; Cai, Yingying; Li, Mei; Luo, Aoxue

doi:10.1016/j.saa.2022.121797

Cited by 38 publications

(17 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the enzyme assay, quercetin was found to inhibit pancreatic α-amylase with an IC 50 value of 57.37 ± 0.9 μg/mL, which is almost comparable with that of the standard compound, acarbose (53.9 ± 0.3 μg/mL) (Supporting Information, Figure S17 and Table S7). This observed inhibition result aligns with the findings reported in the existing literature, which indicate that quercetin can inhibit PPA. ,, PPA and HPA are substantially comparable in terms of their three-dimensional structures. Molecular cloning and primary structural analysis of PPA revealed that it shared the highest similarity to the HPA sequence of all known amylases (87.1%) .…”

Section: Results and Discussionsupporting

confidence: 91%

“…Overall, simulation results showed the stable quercetin–HPA complex in the context of the biological system and therefore illustrated its efficacy as a therapeutic inhibitor. This finding is consistent with the study that remarked quercetin exhibits stable 100 ns MD simulation results against HPA. , …”

Section: Results and Discussionmentioning

confidence: 99%

“…This finding is consistent with the study that remarked quercetin exhibits stable 100 ns MD simulation results against HPA. 36,48 2.4. DFT and Band-Gap Energy.…”

Section: Hydrogen Bondsmentioning

confidence: 99%

“…This observed inhibition result aligns with the findings reported in the existing literature, which indicate that quercetin can inhibit PPA. 26,48,75 PPA and HPA are substantially comparable in terms of their three-dimensional structures. Molecular cloning and primary structural analysis of PPA revealed that it shared the highest similarity to the HPA sequence of all known amylases (87.1%).…”

Section: Pharmacokinetic Analysismentioning

confidence: 99%

See 3 more Smart Citations

In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

Raut,

Upadhyaya,

Bashyal

et al. 2023

ACS Omega

View full text Add to dashboard Cite

Human pancreatic α-amylase (HPA), situated at the apex of the starch digestion hierarchy, is an attractive therapeutic approach to precisely regulate blood glucose levels, thereby efficiently managing diabetes. Polyphenols offer a natural and multifaceted approach to moderate postprandial sugar spikes, with their slight modulation in carbohydrate digestion and potential secondary benefits, such as antioxidant and antiinflammatory effects. Taking into consideration the unfavorable side effects of currently available commercial medications, we aimed to study a library of polyphenols attributed to their remarkable antidiabetic properties and screened the most potent HPA inhibitor via a comprehensive in silico study encompassing molecular docking, molecular mechanics with generalized Born and surface area solvation (MM/GBSA) calculation, molecular dynamics (MD) simulation, density functional theory (DFT) study, and pharmacokinetic properties followed by an in vitro assay. Significant hydrogen bonding with the catalytic triad residues of HPA, prominent MM/ GBSA binding energy of −27.03 kcal/mol, and the stable nature of the protein−ligand complex with regard to 100 ns MD simulation screened quercetin as the best HPA inhibitor. Additionally, quercetin showed strong reactivity in the substrate-binding pocket of HPA and exhibited favorable pharmacokinetic properties with a considerable inhibitory concentration (IC 50 ) of 57.37 ± 0.9 μg/mL against α-amylase. This study holds prospects for HPA inhibition and suggests quercetin as an approach to therapy for diabetes; however, it is imperative to conduct further research.

show abstract

Section: Results and Discussionsupporting

confidence: 91%

Section: Results and Discussionmentioning

confidence: 99%

“…This finding is consistent with the study that remarked quercetin exhibits stable 100 ns MD simulation results against HPA. 36,48 2.4. DFT and Band-Gap Energy.…”

Section: Hydrogen Bondsmentioning

confidence: 99%

Section: Pharmacokinetic Analysismentioning

confidence: 99%

See 2 more Smart Citations

In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

Raut,

Upadhyaya,

Bashyal

et al. 2023

ACS Omega

View full text Add to dashboard Cite

show abstract

“…The structural flexibility of CYP2D6 is evaluated by the RMSF values [58]. As shown in Figure 11b, the RMSF values of CYP2D6–quercetin/hyperoside are within 0.4 nm, indicating that the two complexes are stable [59, 60]. Meanwhile, the partial RMSF values of the two complexes are slightly higher than those of pure CYP2D6, which indicates that the binding of quercetin/hyperoside can enhance the flexibility of the residual CYP2D6 backbone atoms [58].…”

Section: Resultsmentioning

confidence: 99%

Interactions studies of CYP2D6 with quercetin and hyperoside by spectral analysis and molecular dynamics simulations

Wang,

Cui

et al. 2023

Luminescence

View full text Add to dashboard Cite

Some ingredients from herbal medicine can significantly affect the activity of CYP2D6, thus leading to serious interactions between herbs and drugs. Quercetin and hyperoside are active ingredients widely found in vegetables, fruits, and herbal medicines. Quercetin and hyperoside have many biological activities. In this work, the characteristic bindings of CYP2D6 with quercetin/hyperoside are revealed by multi‐spectroscopy analysis, molecular docking, and molecular dynamics simulations. The fluorescence of CYP2D6 is statically quenched by quercetin and hyperoside. The Ka values of CYP2D6‐quercetin/hyperoside range from 104 L·mol‐1, which indicates that these two flavonoids bind moderately to CYP2D6. Meanwhile, quercetin has a stronger quenching ability to CYP2D6 than that of hyperoside. The secondary structure of CYP2D6 is obviously changed by binding with quercetin/hyperoside. The docking results reveal that the quercetin/hyperoside enters the active site of CYP2D6 near Heme, and binds to CYP2D6 by hydrogen bonds and van der Waals forces. The molecular dynamics simulation results indicate that the binding of quercetin/hyperoside can stabilize the two complexes, enhance the flexibility of CYP2D6 backbone atoms, and make a more unfolded and looser structure of CYP2D6.

show abstract

UHPLC‐ESI‐QTOF‐MS metabolite profiles of different extracts from Pelargonium endlicherianum parts and their biological properties based on network pharmacological approaches

Zengin,

Leyva‐Jiménez,

Fernández‐Ochoa

et al. 2024

Archiv der Pharmazie

View full text Add to dashboard Cite

In the present study, we aimed to investigate the chemical profiles and biological activities of different extracts (ethyl acetate, dichloromethane, ethanol, and water) of Pelargonium endlicherianum parts (aerial parts and roots). Free radical scavenging, reducing power, phosphomolybdenum, and metal chelating were assayed for antioxidant properties. To detect enzyme inhibitory properties, cholinesterase, amylase, glucosidase, and tyrosinase were chosen as target enzymes. The ethanol extract of the aerial parts contained higher amounts of total bioactive compounds (120.53 mg GAE/g‐24.46 mg RE/g). The ethanol and water extracts of these parts were tentatively characterized by UHPLC‐ESI‐QTOF‐MS and 95 compounds were annotated. In addition, the highest acetylcholiesterase (3.74 mg GALAE/g) and butyrylcholinesterase (3.92 mg GALAE/g) abilities were observed by the ethanol extract of roots. The water extract from aerial parts exhibited the most pronounced inhibitory effects on multiple cancer cell lines, especially A549 (IC50: 23.2 µg/mL) and HT‐29 (IC50: 27.43 µg/mL) cells. Using network pharmacology, P. endlicherianum compounds were studied against cancer, revealing well‐connected targets such as epidermal growth factor receptor (EGFR), phosphoinositide‐3‐kinase (PI3K), AKT, receptor tyrosine‐protein kinase erbB‐2, and growth factor receptor bound protein 2 (GRB2) with significant impact on cancer‐related pathways. The results could open a new path from natural treasure to functional applications with P. endlicherianum and highlight a new study on other uninvestigated Pelargonium species.

show abstract

Structure-activity relationships and the underlying mechanism of α-amylase inhibition by hyperoside and quercetin: Multi-spectroscopy and molecular docking analyses

Cited by 38 publications

References 45 publications

In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

Interactions studies of CYP2D6 with quercetin and hyperoside by spectral analysis and molecular dynamics simulations

UHPLC‐ESI‐QTOF‐MS metabolite profiles of different extracts from Pelargonium endlicherianum parts and their biological properties based on network pharmacological approaches

Contact Info

Product

Resources

About