In Silico Insight into Potential Anti-Alzheimer’s Disease Mechanisms of Icariin
"> Figure 1
<p>Illustration of icariin docked into acetylcholinesterase (AChE) A chain (<b>a</b>,<b>c</b>) and PDE5 A chain (<b>b</b>,<b>d</b>).</p> "> Figure 2
<p>Icariin’s overall anti-Alzheimer's disease (AD) mechanistic network. Light Red ovals represent predicted icariin’s targets. Blue ovals represent indirectly regulated genes by icariin with experimental results. Yellow arrows represent indirect effect from icariin on these genes. Red arrows represent direct effect from icariin on these targets. The direction of arrows refers to icariin’s effects on targets (activate/upregulate or inhibit/downregulate). A green oval represents approved therapeutic target for AD.</p> "> Figure 3
<p>Average shortest path calculation of inter-subnetworks.</p> ">
Abstract
:1. Introduction
2. Results
2.1. The Putative Protein Targets of Icariin
2.2. The Potential Targets Significantly Correlate with AD-Related Proteins
Uniprot | Gene Symbol | PDB Code | Known Ligand | Icariin | |||
---|---|---|---|---|---|---|---|
Name | MM/GBVI (kcal/mol) | Affinity (pki) | MM/GBVI (kcal/mol) | Affinity (pki) | |||
Q13464 | ROCK1 | 2ETK | Hydroxyfasudil | −21.03 | 8.10 | −33.03 | 14.34 |
P00439 | PAH | 4PAH | Norepinephrine | −26.24 | 7.05 | −44.04 | 7.90 |
Q9HAN9 | NMNAT1 | 1GZU | Nicotinamide Mononucleotide | −27.30 | 12.54 | −23.15 | 17.75 |
Q9BW91 | NUDT9 | 1Q33 | β-d-Glucose | −24.64 | 10.70 | −34.00 | 13.26 |
P50135 | HNMT | 2AOU | Amodiaquine | −26.05 | 6.91 | −22.14 | 6.10 |
Q10588 | BST1 | 1ISG | Adenosine-5′-diphosphate Monothiophosphate | −14.33 | 9.41 | −24.31 | 10.99 |
P06737 | PYGL | 1FA9 | Adenosine Monophosphate | −17.06 | 8.66 | −27.18 | 9.79 |
P00750 | PLAT | 1PK2 | Aminocaproic Acid | −19.90 | 9.71 | −24.92 | 9.30 |
O76074 | PDE5 | 2H42 | Sildenafil | −36.25 | 9.67 | −28.87 | 13.89 |
P04062 | GBA | 2F61 | 2-(Acetylamino)-2-deoxy-a-d-glucopyranose | −16.41 | 5.57 | −21.80 | 11.17 |
P15291 | B4GALT1 | 4EEG | N-Acetyl-d-glucosamine | −19.15 | 8.97 | −34.21 | 10.75 |
P07737 | PFN1 | 1CJF | 7-Hydroxy-4-methyl-3-(2-hydroxy-ethyl)coumarin | −15.42 | 6.69 | −27.05 | 8.67 |
P09012 | SNRPA | 1NU4 | Malonic Acid | −22.16 | 6.52 | −23.86 | 5.34 |
P84077 | ARF1 | 1U81 | 1,3-Propandiol | −37.77 | 4.64 | −43.17 | 11.18 |
Q08209 | PPP3CA | 4F0Z | Myristic Acid | −15.56 | 4.64 | −22.51 | 8.90 |
P13569 | CFTR | 2BBO | Ibuprofen | −8.23 | 6.00 | −6.62 | 11.01 |
P02774 | GC | 1J78 | Cholecalciferol | −10.99 | 5.05 | −21.56 | 6.43 |
P11387 | TOP1 | 1TL8 | Irinotecan | −34.75 | 14.32 | −20.04 | 17.80 |
P19883 | FST | 2B0U | d-Myo-inositol-hexasulphate | −9.54 | 7.03 | −24.81 | 9.78 |
P27695 | APEX1 | 4QHE | Lucanthone | −16.70 | 4.25 | −17.73 | 4.56 |
P22303 | AChE | 1F8U | Mefloquine | −11.44 | 6.54 | −34.86 | 7.97 |
2.3. An Integrated Network for Anti-AD Effects of Icariin
KEGG Pathway | The Number of Icariin’s Targets | p-Value |
---|---|---|
Spliceosome | 5 | 2.26 × 10−6 |
Vibrio cholerae infection | 2 | 3.17 × 10−2 |
Carbohydrate digestion and absorption | 3 | 7.34 × 10−3 |
Legionellosis | 3 | 4.59 × 10−2 |
Oxytocin signaling pathway | 5 | 4.25 × 10−2 |
cGMP-PKG signaling pathway | 5 | 3.09 × 10−2 |
Apoptosis | 5 | 1.14 × 10−2 |
3. Discussion
4. Experimental Section
4.1. Identification of Putative Protein Targets
4.2. Average Shortest Path Calculation
4.3. The Semantic Similarity of Gene Ontology (GO) Profiles
4.4. Pathway Enrichment of Icariin’s Putative Targets
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Cui, Z.; Sheng, Z.; Yan, X.; Cao, Z.; Tang, K. In Silico Insight into Potential Anti-Alzheimer’s Disease Mechanisms of Icariin. Int. J. Mol. Sci. 2016, 17, 113. https://doi.org/10.3390/ijms17010113
Cui Z, Sheng Z, Yan X, Cao Z, Tang K. In Silico Insight into Potential Anti-Alzheimer’s Disease Mechanisms of Icariin. International Journal of Molecular Sciences. 2016; 17(1):113. https://doi.org/10.3390/ijms17010113
Chicago/Turabian StyleCui, Zhijie, Zhen Sheng, Xinmiao Yan, Zhiwei Cao, and Kailin Tang. 2016. "In Silico Insight into Potential Anti-Alzheimer’s Disease Mechanisms of Icariin" International Journal of Molecular Sciences 17, no. 1: 113. https://doi.org/10.3390/ijms17010113