Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. Identification of Active Compounds
2.2. Compound–Target Network
2.3. Compounds–Target–Target Network
2.4. GO Analysis
2.5. Compound–Target–Pathway Network
2.6. Kynurenine Pathway
2.7. Inflammation-Related Pathways
2.8. Molecular Docking
3. Discussion
4. Materials and Methods
4.1. Plant Material
4.2. Establishment of Database
4.3. Extraction and Isolation
4.4. Prediction of Drug-Likeness, Oral Bioavailability, and Blood–Brain Barrier Permeability
4.5. Target Fishing
4.6. Compound–Target Network Construction
4.7. Compounds–Target–Target Network
4.8. Gene Ontology (GO) Analysis
4.9. Compound–Target–Pathway Network
4.10. Molecular Docking
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Targets Abbreviations
Number | PDB ID | Targets | Abbreviations |
1 | 5F19 | Prostaglandin G/H synthase 2 | PTGS2 |
2 | 2HZP | Kynureninase | KYNU |
3 | 3UQU | Beta-secretase 1 | BACE1 |
4 | 3UON | Muscarinic acetylcholine receptor M2 | CHRM2 |
5 | 3O0G | Cyclin-dependent kinase 5 | CDK5 |
6 | 1aqw | Glutathione S-transferase | GSTP1 |
7 | 3DZU | Peroxisome proliferator activated receptor gamma | PPARG |
8 | 5X68 | Kynurenine 3-monooxygenase | KMO |
9 | 1H8F | Glycogen synthase kinase-3 beta | GSK3β |
10 | 4a79 | Monoamine oxidase B | MAOB |
11 | 5CXV | Muscarinic acetylcholine receptor M1 | CHRM1 |
12 | 1SAC | Serum amyloid P-component | APCS |
13 | 2YMD | 5-hydroxytryptamine 4 receptor | HTR4 |
14 | 2FSO | Mitogen-activated protein kinase 14 | MAPK14 |
15 | 1vzj | Acetylcholinesterase | ACHE |
16 | 3IVH | β-Amyloid precursor protein | APP |
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No. | Comp. 1 δC | Comp. 1 δH | Comp. 2 δC | Comp. 2 δH |
---|---|---|---|---|
2 | 145.2 | 78.4 | 5.43 (1H, dd, J = 12.2, 2.8 Hz) | |
3 | 137.0 | 42.0 | 3.21 (1H, dd, J = 12.2, 17.0 Hz) 2.76 (1H, dd, J = 2.8, 17.0 Hz) | |
4 | 172.3 | 197.2 | ||
5 | 123.4 | 7.80 (1H, d, J = 8.8 Hz) | 159.5 | |
6 | 113.9 | 6.97 (1H, d, J = 8.8Hz) | 104.0 | |
7 | 159.4 | 158.9 | ||
8 | 114.4 | 102.0 | ||
9 | 154.1 | 154.7 | ||
10 | 114.5 | 101.0 | ||
1′ | 122.6 | 129.5 | ||
2′ | 129.3 | 8.03 (1H, d, J = 8.9 Hz) | 115.4 | 6.75 (1H, s) |
3′ | 115.5 | 6.93 (1H, d, J = 8.9Hz) | 145.3 | |
4′ | 158.8 | 117.7 | 6.90 (1H, s) | |
5′ | 115.5 | 6.93 (1H, d, J = 8.9Hz) | 145.7 | |
6′ | 129.3 | 8.03 (1H, d, J = 8.9 Hz) | 114.2 | 6.75 (1H, s) |
1″ | 21.9 | 3.56 (2H, d, J = 6.6 Hz) | 115.3 | 6.44 (1H, d, J = 10.0 Hz) |
2″ | 122.1 | 5.22 (1H, t, J = 6.6 Hz) | 126.7 | 5.63 (1H, d, J = 10.0 Hz) |
3″ | 131.5 | 77.9 | ||
4″ | 25.9 | 1.77 (s, 3H) | 28.0 | 1.38 (s, 3H) |
5″ | 17.9 | 1.63(s, 3H) | 27.9 | 1.41((s, 3H) |
6-Me | 7.4 | 1.89 (s, 3H) |
Comp. | QPlogS | QPPCaco | QPlogBB | QPP MDCK | Percent Human Oral Absorption | Rule of Five | Rule of Three |
---|---|---|---|---|---|---|---|
C1 | −4.993 | 287.747 | −1.28 | 128.708 | 86.403 | 0 | 0 |
C2 | −5.733 | 178.660 | −1.35 | 76.892 | 84.863 | 0 | 1 |
C3 | −3.294 | 4887.536 | 0.23 | 2749 | 100 | 0 | 0 |
C4 | −5.055 | 337.098 | −1.34 | 152.725 | 90.744 | 0 | 0 |
C5 | −0.393 | 514.138 | −0.52 | 241.025 | 73.539 | 0 | 0 |
C6 | −1.542 | 328.798 | −0.76 | 148.665 | 78.23 | 0 | 0 |
C7 | −1.08 | 2646.027 | −0.133 | 1416.199 | 100 | 0 | 0 |
C8 | −1.08 | 2646.103 | −0.13 | 1416.243 | 100 | 0 | 0 |
C9 | −1.881 | 1220.263 | 0.50 | 678.697 | 96.387 | 0 | 0 |
C10 | −0.22 | 497.093 | 0.61 | 516.978 | 80.741 | 0 | 0 |
C11 | 1.168 | 1710.644 | 0.17 | 1785.53 | 90.664 | 0 | 0 |
C12 | −1.756 | 1202 | −0.22 | 603.556 | 87.474 | 0 | 0 |
C13 | −1.554 | 116.972 | −0.62 | 61.872 | 77.047 | 0 | 0 |
C14 | −1.694 | 97.467 | −0.99 | 50.8 | 70.752 | 0 | 0 |
C15 | −1.171 | 192.969 | −1.44 | 83.57 | 62.799 | 0 | 0 |
C16 | −1.228 | 223.474 | −1.47 | 97.936 | 64.567 | 0 | 1 |
C17 | −4.368 | 125.867 | −1.72 | 52.658 | 79.335 | 0 | 1 |
C18 | −5.121 | 216.221 | −1.26 | 94.505 | 86.586 | 0 | 0 |
C19 | −4.656 | 159.964 | −1.65 | 68.233 | 82.202 | 0 | 1 |
C20 | −3.685 | 127.628 | −1.52 | 53.454 | 78.142 | 0 | 1 |
C21 | −4.863 | 196.428 | −1.26 | 85.19 | 85.179 | 0 | 0 |
C22 | −3.737 | 457.384 | −0.95 | 212.4 | 90.08 | 0 | 1 |
C23 | −4.444 | 220.66 | −1.23 | 96.604 | 84.383 | 0 | 0 |
C24 | −4.489 | 232.352 | −1.23 | 102.148 | 83.481 | 0 | 0 |
C25 | −4.637 | 1114.163 | −0.481 | 556.027 | 100 | 0 | 0 |
C26 | −5.976 | 1562.723 | −0.49 | 801.518 | 100 | 1 | 1 |
C27 | −6.127 | 1015.613 | −0.60 | 503.063 | 100 | 0 | 1 |
C28 | −3.871 | 640.678 | −1.09 | 305.739 | 93.583 | 0 | 1 |
No. | Name | Structure | No. | Name | Structure |
---|---|---|---|---|---|
C1 | compound 1 | C15 | 4-hydroxy-3-methoxyphenyl-β-d-glucopyranoside | ||
C2 | compound 2 | C16 | koaburaside | ||
C3 | harmine | C17 | noranhydroicaritin | ||
C4 | 4,4′-diphenylmethane-bislmethy carbamate | C18 | desmodin B | ||
C5 | nicotinamide | C19 | cudraflavanone B | ||
C6 | 5-hydroxy-indole-3-aldehyde | C20 | leachianone G | ||
C7 | N-chloromethyl-N,N-dimethyltryptamine | C21 | desmodol | ||
C8 | N,N-dimethyltryptamine N12-oxide | C22 | caudatan C | ||
C9 | N,N-dimethyltryptamine | C23 | citrusinol | ||
C10 | nicotinic acid | C24 | yukovanol | ||
C11 | ammothamnine | C25 | caudatan A | ||
C12 | loliolide | C26 | 3β-12-ene-3, 23, 28-triol | ||
C13 | salicylic acid | C27 | soyasapogenel B | ||
C14 | ferulic acid | C28 | (+)-5′-methoxyisolariciresinol-9-O-β-d-glucopyranoside |
Compound | PTGS2 | KYNU | BACE1 | CDK5 | CHRM2 |
---|---|---|---|---|---|
Reference | −279.275 | −71.135 | −269.837 | −157.913 | −130.289 |
1 | −109.826 | −82.362 | −131.327 | −100.114 | −124.923 |
2 | −109.851 | −81.0566 | −125.875 | −103.123 | −113.16c |
3 | −101.917 | −90.059 | −97.622 | −81.515 | −102.699 |
4 | −116.921 | −112.357 | −147.607 | −125.264 | −120.443 |
5 | −66.7496 | −59.008 | −61.787 | −83.45 | −64.733 |
6 | −87.8179 | −85.553 | −89.709 | −71.066 | −87.349 |
7 | −97.7527 | −80.036 | −104.692 | −87.507 | −113.467 |
8 | −96.806 | −90.1924 | −101.014 | −82.776 | −103.683 |
9 | −95.682 | −79.2415 | −94.954 | −83.71 | −98.256 |
10 | −87.768 | −47.2166 | −96.669 | −73.057 | −93.652 |
11 | −83.11 | −30.309 | −78.291 | −58.436 | −77.146 |
12 | −100.12 | −61.922 | −87.5 | −77.206 | −87.393 |
13 | −74.49 | −66.975 | −67.683 | −53.451 | −66.144 |
14 | −101.205 | −89.905 | −103.201 | −84.782 | −96.424 |
15 | −91.99 | −65.687 | −101.422 | −80.586 | −103.666 |
16 | −97.489 | −64.878 | −107.982 | −84.402 | −107.419 |
17 | −113.147 | −79.252 | −131.154 | −103.973 | −126.566 |
18 | −105.505 | −82.359 | −122.934 | −97.775 | −109.951 |
19 | −121.982 | −94.5721 | −138.589 | −113.973 | −109.814 |
20 | −118.492 | −95.216 | −128.598 | −104.169 | −124.998 |
21 | −105.56 | −80.545 | −127.578 | −102.149 | −113.791 |
22 | −101.112 | −63.776 | −126.693 | −83.45 | −117.44 |
23 | −100.213 | −64.122 | −122.083 | −96.788 | −111.528 |
24 | −99.225 | −63.626 | −119.269 | −91.528 | −110.426 |
25 | −88.806 | −55.989 | −69.709 | −73.446 | −116.637 |
26 | −89.21 | −74.515 | −95.219 | −98.8 | −67.588 |
27 | −90.942 | −52.395 | −83.509 | −101.319 | −68.174 |
28 | −118.408 | −72.669 | −136.226 | −107.887 | −133.31 |
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Sun, Y.-w.; Wang, Y.; Guo, Z.-f.; Du, K.-c.; Meng, D.-l. Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer’s Disease. Molecules 2019, 24, 1499. https://doi.org/10.3390/molecules24081499
Sun Y-w, Wang Y, Guo Z-f, Du K-c, Meng D-l. Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer’s Disease. Molecules. 2019; 24(8):1499. https://doi.org/10.3390/molecules24081499
Chicago/Turabian StyleSun, Yi-wei, Yue Wang, Zi-feng Guo, Kai-cheng Du, and Da-li Meng. 2019. "Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer’s Disease" Molecules 24, no. 8: 1499. https://doi.org/10.3390/molecules24081499