Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure
Abstract
:1. Introduction
2. Results
2.1. Network Pharmacology-Based Analysis
2.1.1. Component Analysis of TFDM
2.1.2. Compounds, Disease Target Prediction, and Construction of PPI Network
2.1.3. Construction of C-T Network
2.1.4. Gene Ontology Enrichment Analysis
2.1.5. KEGG Pathway Enrichment Analysis
2.1.6. Computational Validation of Selected Compound–Target Interactions
2.2. Effects of TFDM
2.2.1. Effects of TFDM on Blood Glucose, Blood pressure, and Running Distance
2.2.2. Effects of TFDM on Cardiac Function
2.2.3. Effects of TFDM on Cardiac Histology
3. Discussion
4. Materials and Methods
4.1. Network Pharmacology-Based Approach for the Potential Actions of TFDM on HF
4.1.1. Screening of Active Compounds
4.1.2. Target Prediction
4.1.3. Protein–Protein Interaction (PPI) Network and Compound–Target (C-T) Network Construction
4.1.4. Gene Ontology, KEGG Pathway Enrichment, and C-T Network Construction
4.1.5. Target Identification Based on Molecular Docking
4.2. In Vivo Experiments to Validate the Effect of TFDM on HF
4.2.1. Reagents and Animals
4.2.2. Establishment of HFpEF Experimental Model
4.2.3. Conventional Echocardiography and Doppler Imaging
4.2.4. Tail-Cuff Blood Pressure Recordings
4.2.5. Intraperitoneal Glucose Tolerance Test
4.2.6. Exercise Exhaustion Test
4.2.7. Histology
4.2.8. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound Name | OB (%) | DL | References |
---|---|---|---|
Apigenin | 23.06 | 0.21 | [17] |
Acacetin | 34.97 | 0.24 | [12,18] |
Luteolin | 36.16 | 0.25 | [17] |
Salvigenin | 49.07 | 0.33 | [17] |
Chryseriol | 35.85 | 0.27 | [19] |
Diosmetin | 31.14 | 0.27 | [12] |
Isorhamnetin | 49.6 | 0.31 | [17] |
Kaempferol | 41.88 | 0.24 | [19] |
Quercetin | 46.43 | 0.28 | [17] |
Tilianin | 19.66 | 0.79 | [14,17] |
Astragalin | 14.03 | 0.74 | [20] |
NO | Compound Name | PubChem CID | Structure |
---|---|---|---|
1 | Apigenin | 5280443 | |
2 | Acacetin | 5280442 | |
3 | Luteolin | 5280445 | |
4 | Salvigenin | 161271 | |
5 | Chryseriol | 5280666 | |
6 | Diosmetin | 5281612 | |
7 | Isorhamnetin | 5281654 | |
8 | Kaempferol | 5280863 | |
9 | Quercetin | 5280343 | |
10 | Tilianin | 5321954 | |
11 | Astragalin | 5282102 | |
Gene ID | Gene Name | Gene Symbol | Degree |
---|---|---|---|
5743 | Prostaglandin-endoperoxide synthase 2 | PTGS2 | 11 |
4843 | Nitric oxide synthase 2 | NOS2 | 10 |
5742 | Prostaglandin-endoperoxide synthase 1 | PTGS1 | 10 |
367 | Androgen receptor | AR | 9 |
5294 | Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic subunit gamma | PIK3CG | 9 |
7124 | Tumor necrosis factor | TNF | 8 |
2099 | Estrogen receptor 1 | ESR1 | 7 |
3569 | Interleukin 6 | IL6 | 7 |
7498 | Xanthine dehydrogenase | XDH | 7 |
3553 | Interleukin 1 beta | IL-1β | 6 |
Compound | TNF | IL-6 | IL-1β | NOS2 | PTGS2 |
---|---|---|---|---|---|
Apigenin | −8.2 | −8.9 | −7.3 | −10.1 | −8.7 |
Acacetin | −8.2 | −8.6 | −7.3 | −10.2 | −8.3 |
Luteolin | −8.4 | −9.2 | −7.5 | −9.8 | −8.6 |
Salvigenin | −7.9 | −8.4 | −7.1 | −9.1 | −8.3 |
Chryseriol | −8.4 | −8.8 | −7.3 | −9.8 | −8.7 |
Diosmetin | −8.3 | −8.7 | −7.4 | −10.1 | −8.4 |
Isorhamnetin | −8.0 | −8.7 | −7.2 | −9.9 | −9.1 |
Kaempferol | −7.8 | −8.8 | −7.2 | −9.9 | −9.0 |
Quercetin | −8.2 | −9.3 | −7.4 | −9.7 | −9.0 |
Tilianin | −8.0 | −9.4 | −7.7 | −10.9 | −9.4 |
Astragalin | −7.4 | −7.6 | −7.8 | −9.8 | −8.7 |
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Dawuti, A.; Sun, S.; Wang, R.; Gong, D.; Yuan, T.; Zhang, L.; Yang, S.; Xing, J.; Zheng, R.; Lu, Y.; et al. Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure. Int. J. Mol. Sci. 2022, 23, 8409. https://doi.org/10.3390/ijms23158409
Dawuti A, Sun S, Wang R, Gong D, Yuan T, Zhang L, Yang S, Xing J, Zheng R, Lu Y, et al. Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure. International Journal of Molecular Sciences. 2022; 23(15):8409. https://doi.org/10.3390/ijms23158409
Chicago/Turabian StyleDawuti, Awaguli, Shuchan Sun, Ranran Wang, Difei Gong, Tianyi Yuan, Li Zhang, Shiying Yang, Jianguo Xing, Ruifang Zheng, Yang Lu, and et al. 2022. "Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure" International Journal of Molecular Sciences 23, no. 15: 8409. https://doi.org/10.3390/ijms23158409