Deciphering the Efficacy and Mechanism of Astragalus membranaceus on High Altitude Polycythemia by Integrating Network Pharmacology and In Vivo Experiments
Abstract
:1. Introduction
2. Materials and Methods
2.1. Network Pharmacology Analysis
2.1.1. Collection and Analysis of Targets of AM and HAPC
2.1.2. Protein–Protein Interactions (PPI) Network and Core Target Analysis
2.1.3. Analysis of Pathway Enrichment
2.2. Molecular Docking of Active Components-Core Targets
2.3. Animals
2.4. Establishment of HAPC Model
2.5. Blood Counts
2.6. Organ Morphology
2.7. Cell Preparation and Flow Cytometry
2.8. Quantitative Real-Time PCR (qRT-PCR)
2.9. Statistical Analysis
3. Results
3.1. Identification of Components in AM and Target Prediction
3.2. Screened Targets Related HAPC
3.3. Identified 36 Common Targets between AM and HAPC
3.4. Analyzed Core Targets of AM on HAPC
3.5. Enriched Pathway Analysis of Common Targets and Core Targets
3.6. Molecular Docking Verified the Binding Mode of Compounds to Targets
3.7. AM Relieved Hematological Abnormalities in HAPC Mice
3.8. AM Alleviated Hypoxia-Induced Organ Damage
3.9. AM Inhibited Erythroid Differentiation of HSCs in BM
3.10. The Effect of AM on the HIF-1 Signaling Pathway in HAPC Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Target Gene | Primer Sequence |
---|---|
β-actin | Forward 5′-GCTGTATTCCCCTCCATCGTG-3′ |
Reverse 5′-CACGGTTGGCCTTAGGGTTCAG-3′ | |
VEGFA | Forward 5′-ATCGAGTACATCTTCAAGCCAT-3′ |
Reverse 5′-GTGAGGTTTGATCCGCATAATC-3′ | |
HIF-1α | Forward 5′-TGACGGCGACAGGGTTTACA-3′ |
Reverse 5′-AATATGGCCCGTGCAGTGAA-3′ | |
TNF-α | Forward 5′-ATGTCTCAGCCTCTTCTCATTC-3′ |
Reverse 5′-GCTTGTCACTCGAATTTTGAGA-3′ | |
IL-6 | Forward 5′-TAGTCCTTCCTACCCCAATTTCC-3′ |
Reverse 5′-TTGGTCCTTAGCCACTCCTTC-3′ | |
IL-1B | Forward 5′-CACTACAGGCTCCGAGATGAACAAC-3′ |
Reverse 5′-TGTCGTTGCTTGGTTCTCCTTGTAC-3′ | |
Gata-1 | Forward 5′-GTCCTCACCATCAGATTCCACAG-3′ |
Reverse 5′-GAGTGCCGTCTTGCCATAGG-3′ | |
PU.1 | Forward 5′-AGGAGTCTTCTACGACCTGGA-3′ |
Reverse 5′-GAAGGCTTCATAGGGAGCGAT-3′ | |
IFN-γ | Forward 5′-GCCACGGCACAGTCATTGA-3′ |
Reverse 5′-TGCTGATGGCCTGATTGTCTT-3′ | |
AKT1 | Forward 5′-GCCCTCAAGTACTCATTCCAG-3′ |
Reverse 5′-ACACAATCTCCGCACCATAG-3′ | |
SEPRINE1 | Forward 5′-GGAATAAGGCGAGTTGGAAGAA-3′ |
Reverse 5′ GGCCGTTCGATAATCGGTCTAT-3′ | |
NOS2 | Forward 5′-GGAGTGACGGCAAACATGACT-3′ |
Reverse 5′-TCGATGCACAACTGGGTGAAC-3′ | |
HMOX1 | Forward 5′-GATAGAGCGCAACAAGCAGAA-3′ |
Reverse 5′-CAGTGAGGCCCATACCAGAAG-3′ | |
NOS3 | Forward 5′-TGTGACCCTCACCGCTACAA-3′ |
Reverse 5′-GCACAATCCAGGCCCAATC-3′ | |
EPO | Forward 5′-ACTCTCCTTGCTACTGATTCCT-3′ |
Reverse 5′-ATCGTGACATTTTCTGCCTCC-3′ |
Mol ID a | Mol Name b | OB c (%) | DL d | PubChem ID |
---|---|---|---|---|
MOL000098 | Quercetin | 46.43 | 0.28 | 5280343 |
MOL000211 | Mairin | 55.38 | 0.78 | 64971 |
MOL000239 | Kumatakenin | 50.83 | 0.3 | 5318869 |
MOL000296 | Hederagenin | 36.91 | 0.75 | 73299 |
MOL000354 | Isorhamnetin | 49.6 | 0.31 | 5281654 |
MOL000387 | Bifendate | 31.1 | 0.67 | 108213 |
MOL000392 | Formononetin | 69.67 | 0.21 | 5280378 |
MOL000398 | Isoflavanone | 109.99 | 0.3 | 160767 |
MOL000417 | Calycosin | 47.75 | 0.24 | 5280448 |
MOL000422 | Kaempferol | 41.88 | 0.24 | 5280863 |
MOL000433 | Folsaeure (FA) | 68.96 | 0.7057 | 6037 |
MOL000442 | Sucrose | 39.05 | 0.48 | 5316760 |
MOL000371 | 3,9-di-O-methylnissolin | 53.74 | 0.48 | 15689655 |
MOL000374 | 5′-hydroxyiso-muronulatol-2′,5′-di-O-glucoside | 41.72 | 0.7 | NA |
MOL000378 | 7-O-methylisomucronulatol | 74.69 | 0.3 | 15689652 |
MOL000379 | Methylnissolin-3-O-Glucoside | 36.74 | 0.92 | 74977390 |
MOL000380 | Methylnissolin | 64.26 | 0.42 | 14077830 |
MOL000438 | (R)-Isomucronulatol | 67.67 | 0.26 | 10380176 |
MOL000439 | Isomucronulatol-7,2′-di-O-glucosiole | 49.28 | 0.62 | 15689653 |
MOL000033 | (24S)-24-Propylcholesta-5-ene-3beta-ol | 36.23 | 0.78 | 15976101 |
No. | Gene Name | Protein Name | PubChem ID |
---|---|---|---|
1 | NOS2 | nitric oxide synthase 2 | P35228 |
2 | AR | androgen receptor | P10275 |
3 | ESR1 | estrogen receptor 1 | P03372 |
4 | PPARG | peroxisome proliferator activated receptor gamma | P37231 |
5 | PTPN6 | protein tyrosine phosphatase non-receptor type 6 | P29350 |
6 | F2 | coagulation factor II, thrombin | P00734 |
7 | NOS3 | nitric oxide synthase 3 | P29474 |
8 | ADRB2 | adrenoceptor beta 2 | P07550 |
9 | AKT1 | AKT serine/threonine kinase 1 | P31749 |
10 | BCL2 | BCL2 apoptosis regulator | P10415 |
11 | TNF | tumor necrosis factor | P01375 |
12 | HMOX1 | heme oxygenase 1 | P09601 |
13 | GSTM1 | glutathione S-transferase mu 1 | P09488 |
14 | VEGFA | vascular endothelial growth factor A | P15692 |
15 | IL10 | interleukin 10 | P22301 |
16 | IL6 | interleukin 6 | P05231 |
17 | CASP8 | caspase 8 | Q14790 |
18 | SOD1 | superoxide dismutase 1 | P00441 |
19 | HIF1A | hypoxia inducible factor 1 subunit alpha | Q16665 |
20 | F3 | coagulation factor III, tissue factor | P13726 |
21 | IL1B | interleukin 1 beta | P01584 |
22 | CXCL8 | C-X-C motif chemokine ligand 8 | P10145 |
23 | THBD | thrombomodulin | P07204 |
24 | SERPINE1 | serpin family E member 1 | P05121 |
25 | IFNG | interferon gamma | P01579 |
26 | MPO | myeloperoxidase | P05164 |
27 | PPARA | peroxisome proliferator activated receptor alpha | Q07869 |
28 | CRP | C-reactive protein | P02741 |
29 | ABCB1 | ATP binding cassette subfamily B member 1 | P08183 |
30 | SLC2A1 | solute carrier family 2 member 1 | P11166 |
31 | MTHFR | methylenetetrahydrofolate reductase | P42898 |
32 | HSPA4 | heat shock protein family A | P34932 |
33 | CA1 | carbonic anhydrase 1 | P00915 |
34 | ABCB1 | ATP-dependent translocase ABCB1 | P08183 |
35 | HMGB1 | high mobility group protein B1 | P09429 |
36 | SLC2A1 | solute carrier family 2, facilitated glucose transporter member 1 | P11166 |
Gene Name | DC a | BC b | CC c |
---|---|---|---|
TNF | 19 | 133.5863 | 0.157658 |
AKT1 | 17 | 128.2761 | 0.154185 |
IL6 | 18 | 97.26547 | 0.156951 |
VEGFA | 13 | 96.63991 | 0.153509 |
IL1B | 16 | 72.26746 | 0.154867 |
SERPINE1 | 9 | 59.16642 | 0.148936 |
CRP | 11 | 54.56417 | 0.150862 |
NOS3 | 9 | 39.74613 | 0.150215 |
HIF1A | 11 | 34.52048 | 0.150215 |
NOS2 | 9 | 18.6465 | 0.150215 |
IFNG | 8 | 17.08651 | 0.145833 |
HMOX1 | 7 | 13.84444 | 0.147059 |
CXCL8 | 10 | 13.132 | 0.151515 |
ESR1 | 7 | 12.39106 | 0.145228 |
Core Targets | PDB ID a | Compounds | Affinity (kcal/mol) |
---|---|---|---|
TNF | 2E7A | Quercetin | −6.807 |
Kaempferol | −6.581 | ||
AKT1 | 1UNQ | Quercetin | −7.517 |
Kaempferol | −7.351 | ||
Isorhamnetin | −7.456 | ||
IL6 | 1ALU | Quercetin | −7.495 |
VEGFA | 1MKK | Quercetin | −7.804 |
IL1B | 5R8Q | Quercetin | −7.277 |
HIF1A | 4H6J | Quercetin | −7.090 |
SERPINE1 | 1LJ5 | Quercetin | −7.512 |
Folsaeure (FA) | −8.197 | ||
CRP | 3PVN | Quercetin | −7.399 |
CXCL8 | 4XDX | Quercetin | −7.367 |
IFNG | 1FYH | Quercetin | −7.295 |
NOS2 | 3E7G | Formononetin | −7.922 |
Kumatakenin | −8.035 | ||
Isorhamnetin | −7.665 | ||
Calycosin | −8.134 | ||
Kaempferol | −7.604 | ||
3,9-di-O-methylnissolin | −8.069 | ||
7-O-methylisomucronulatol | −8.097 | ||
Methylnissolin | −7.966 | ||
NOS3 | 4D1P | Formononetin | −7.696 |
Quercetin | −7.719 | ||
Isorhamnetin | −7.964 | ||
Kaempferol | −7.461 | ||
3,9-di-O-methylnissolin | −7.877 | ||
7-O-methylisomucronulatol | −8.235 | ||
Folsaeure (FA) | −9.103 | ||
HMOX1 | 1N45 | Quercetin | −7.604 |
Isorhamnetin | −7.509 | ||
Kaempferol | −7.319 | ||
ESR1 | 7NFB | Formononetin | −6.988 |
Isorhamnetin | −7.148 | ||
Calycosin | −8.170 | ||
Kaempferol | −7.187 | ||
3,9-di-O-methylnissolin | −7.308 | ||
7-O-methylisomucronulatol | −7.375 | ||
Methylnissolin | −6.975 |
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Liu, X.; Zhang, H.; Yan, J.; Li, X.; Li, J.; Hu, J.; Shang, X.; Yang, H. Deciphering the Efficacy and Mechanism of Astragalus membranaceus on High Altitude Polycythemia by Integrating Network Pharmacology and In Vivo Experiments. Nutrients 2022, 14, 4968. https://doi.org/10.3390/nu14234968
Liu X, Zhang H, Yan J, Li X, Li J, Hu J, Shang X, Yang H. Deciphering the Efficacy and Mechanism of Astragalus membranaceus on High Altitude Polycythemia by Integrating Network Pharmacology and In Vivo Experiments. Nutrients. 2022; 14(23):4968. https://doi.org/10.3390/nu14234968
Chicago/Turabian StyleLiu, Xiru, Hao Zhang, Jinxiao Yan, Xiang Li, Jie Li, Jialu Hu, Xuequn Shang, and Hui Yang. 2022. "Deciphering the Efficacy and Mechanism of Astragalus membranaceus on High Altitude Polycythemia by Integrating Network Pharmacology and In Vivo Experiments" Nutrients 14, no. 23: 4968. https://doi.org/10.3390/nu14234968