Journal of Traditional Chinese Medicine ›› 2025, Vol. 45 ›› Issue (6): 1353-1365.DOI: 10.19852/j.cnki.jtcm.2025.06.014
• Original Articles • Previous Articles Next Articles
ZHAO Yumin1,2,3, ZHANG Yuliang4, WANG Guozi4, LIU Xizan4, ZHAO Pengmin4, ZHAO Mengjun4, LI Zhaoxia5, DI Haixia4
Received:2024-07-12
Accepted:2024-10-28
Online:2025-12-15
Published:2025-11-24
Contact:
DI Haixia, 4th Hematology Department, Langfang Hospital of Traditional Chinese Medicine, Langfang 065000 China. dhx-55555@163.com, Telephone: +86-18031603706
Supported by:ZHAO Yumin, ZHANG Yuliang, WANG Guozi, LIU Xizan, ZHAO Pengmin, ZHAO Mengjun, LI Zhaoxia, DI Haixia. Network pharmacology-based analysis of the antithrombotic clinical efficacy and antithrombotic mechanism of Huoxue Jiedu prescription (活血解毒方) in the treatment of polycythemia vera with heat toxin and blood stasis syndrome[J]. Journal of Traditional Chinese Medicine, 2025, 45(6): 1353-1365.
| Target | UniProt ID | Degree Layout | BC | CC | Target | UniProt ID | Degree Layout | BC | CC |
|---|---|---|---|---|---|---|---|---|---|
| AKT1 | P31749 | 282 | 0.0026 | 0.45 | ALB | P02768 | 268 | 0.0033 | 0.9545 |
| TP53 | Q12888 | 284 | 0.0045 | 1.0 | EGFR | P00533 | 260 | 0.0045 | 1.0 |
| TNF | P01375 | 282 | 0.0045 | 1.0 | STAT3 | P40763 | 258 | 0.0045 | 1.0 |
| GAPDH | P04406 | 278 | 0.0045 | 1.0 | IL1B | P01584 | 252 | 0.0032 | 0.9545 |
Table 1 Related characteristics of key targets
| Target | UniProt ID | Degree Layout | BC | CC | Target | UniProt ID | Degree Layout | BC | CC |
|---|---|---|---|---|---|---|---|---|---|
| AKT1 | P31749 | 282 | 0.0026 | 0.45 | ALB | P02768 | 268 | 0.0033 | 0.9545 |
| TP53 | Q12888 | 284 | 0.0045 | 1.0 | EGFR | P00533 | 260 | 0.0045 | 1.0 |
| TNF | P01375 | 282 | 0.0045 | 1.0 | STAT3 | P40763 | 258 | 0.0045 | 1.0 |
| GAPDH | P04406 | 278 | 0.0045 | 1.0 | IL1B | P01584 | 252 | 0.0032 | 0.9545 |
| Mol ID | Molecule name | Degree | BC | CC |
|---|---|---|---|---|
| MOL000422 | Kaempferol | 222 | 0.0063 | 0.4027 |
| MOL000098 | Quercetin | 185 | 0.0043 | 0.4007 |
| MOL002714 | Baicalein | 152 | 0.0058 | 0.4017 |
| MOL000173 | Wogonin | 108 | 0.0032 | 0.3998 |
| MOL008206 | Moslosooflavone | 80 | 0.0029 | 0.4027 |
| MOL000006 | Luteolin | 78 | 0.0029 | 0.4017 |
| MOL002915 | Salvigenin | 78 | 0.0028 | 0.4017 |
| MOL012266 | Rivularin | 70 | 0.0032 | 0.3950 |
| MOL002719 | 6-Hydroxynaringenin | 52 | 0.0021 | 0.3832 |
| MOL012246 | 5,7,4'-Trihydroxy-8-methoxyflavanone | 44 | 0.0017 | 0.3808 |
Table 2 Related characteristics of key compounds
| Mol ID | Molecule name | Degree | BC | CC |
|---|---|---|---|---|
| MOL000422 | Kaempferol | 222 | 0.0063 | 0.4027 |
| MOL000098 | Quercetin | 185 | 0.0043 | 0.4007 |
| MOL002714 | Baicalein | 152 | 0.0058 | 0.4017 |
| MOL000173 | Wogonin | 108 | 0.0032 | 0.3998 |
| MOL008206 | Moslosooflavone | 80 | 0.0029 | 0.4027 |
| MOL000006 | Luteolin | 78 | 0.0029 | 0.4017 |
| MOL002915 | Salvigenin | 78 | 0.0028 | 0.4017 |
| MOL012266 | Rivularin | 70 | 0.0032 | 0.3950 |
| MOL002719 | 6-Hydroxynaringenin | 52 | 0.0021 | 0.3832 |
| MOL012246 | 5,7,4'-Trihydroxy-8-methoxyflavanone | 44 | 0.0017 | 0.3808 |
Figure 2 Functional enrichment analysis of the potential targets of Huoxue Jiedu prescription for the treatment of PV A: GO enrichment analysis; B: KEGG pathway analysis. BC: betweenness centrality; CC: closeness centrality; MF: molecular function.?
| Target | PDB-ID | Ligand-ID | Resolution | Target | PDB-ID | Ligand-ID | Resolution |
|---|---|---|---|---|---|---|---|
| AKT1 | 8PP9 | 4IM | 1.73 ? | EGFR | 8A2D | KXY | 1.11 ? |
| TP53 | 8QZD | XDZ | 1.30 ? | STAT3 | 8XAM | XRH | 1.30 ? |
| TNF | 8BRO | R7E | 1.55 ? | IL1B | 8TWJ | UDP | 1.90 ? |
| GAPDH | 8J40 | CLM | 1.57 ? | PI3K | 8XPV | 4Z5 | 1.55 ? |
| ALB | 8BSG | DIF | 1.89 ? |
Table 3 Information on nine proteins included in molecular docking
| Target | PDB-ID | Ligand-ID | Resolution | Target | PDB-ID | Ligand-ID | Resolution |
|---|---|---|---|---|---|---|---|
| AKT1 | 8PP9 | 4IM | 1.73 ? | EGFR | 8A2D | KXY | 1.11 ? |
| TP53 | 8QZD | XDZ | 1.30 ? | STAT3 | 8XAM | XRH | 1.30 ? |
| TNF | 8BRO | R7E | 1.55 ? | IL1B | 8TWJ | UDP | 1.90 ? |
| GAPDH | 8J40 | CLM | 1.57 ? | PI3K | 8XPV | 4Z5 | 1.55 ? |
| ALB | 8BSG | DIF | 1.89 ? |
Figure 3 Heat map for docking score AKT1: serine/threonine-protein kinase AKT1; EGFR: epidermal growth factor receptor; TNF: tumor necrosis factor; ALB: albumin gene; albumin; GAPDH: glyceraldehyde -3-phosphate dehydrogenase; TP53: tumor protein 53; IL1B: Interleukin-1 beta; STAT3: Signal transducer and activator of transcription 3; PI3K: phosphatidyqinositol-3 kinase.
Figure 4 Binding modes of targets and compounds A: AKT1 and MOL002719; B: PI3K and MOL000006; C: STAT3 and MOL008206; D: TP53 and MOL000422. AKT1: serine/threonine-protein kinase AKT1; TP53: tumor protein 53; STAT3: signal transducer and activator of transcription 3; PI3K: phosphatidyqinositol-3 kinase.
| Item | Control (n = 30) | Treatment (n = 30) | |
|---|---|---|---|
| n | 30 | 30 | |
| Gender (male/female, n) | 17/13 | 19/11 | |
| Average age (years) | 51±12 | 51±13 | |
| Previous history of thrombosis/bleeding (n) | 16 | 17 | |
| ECOG (n) | 0 | 20 | 18 |
| 1 | 9 | 10 | |
| 2+ | 1 | 2 | |
Table 4 Comparison of general data between the two groups ($\bar{x}$ ± s)
| Item | Control (n = 30) | Treatment (n = 30) | |
|---|---|---|---|
| n | 30 | 30 | |
| Gender (male/female, n) | 17/13 | 19/11 | |
| Average age (years) | 51±12 | 51±13 | |
| Previous history of thrombosis/bleeding (n) | 16 | 17 | |
| ECOG (n) | 0 | 20 | 18 |
| 1 | 9 | 10 | |
| 2+ | 1 | 2 | |
| Group | Degree of dark reddish complexion | Condition of petechiae and ecchymosis | Tongue | |||||
|---|---|---|---|---|---|---|---|---|
| Before treatment | After treatment | Before treatment | After treatment | Before treatment | Before treatment | |||
| Control (n = 30) | 5.20±0.41 | 3.27±0.26 | 4.48±0.23 | 2.31±0.27 | 2.37±0.29 | 1.43±0.47 | ||
| Treatment (n = 30) | 5.17±0.38a | 2.53±0.33ab | 4.37±0.26a | 1.31±0.31 | 2.41±0.32 | 0.88±0.45 | ||
Table 5 Comparison of TCM blood stasis syndrome scores between the two groups ($\bar{x}$ ± s)
| Group | Degree of dark reddish complexion | Condition of petechiae and ecchymosis | Tongue | |||||
|---|---|---|---|---|---|---|---|---|
| Before treatment | After treatment | Before treatment | After treatment | Before treatment | Before treatment | |||
| Control (n = 30) | 5.20±0.41 | 3.27±0.26 | 4.48±0.23 | 2.31±0.27 | 2.37±0.29 | 1.43±0.47 | ||
| Treatment (n = 30) | 5.17±0.38a | 2.53±0.33ab | 4.37±0.26a | 1.31±0.31 | 2.41±0.32 | 0.88±0.45 | ||
| Group | Time | HGB (g/L) | PLT (×109/L) | HCT (%) | WBC (×109/L) |
|---|---|---|---|---|---|
| Control (n = 30) | Before treatment | 215.8±36.3 | 251.3±53.8 | 62.4±11.9 | 14.4±2.1 |
| After treatment | 158.7±28.6a | 190.7±31.3a | 28.1±5.4a | 8.3±1.2a | |
| Treatment (n = 30) | Before treatment | 199.6±26.6 | 240.7±50.6 | 58.91±11.00 | 14.2±2.4 |
| After treatment | 139.0±22.4ab | 169.5±39.5ab | 25.6±5.7ab | 6.2±1.1ab |
Table 6 Comparison of blood parameters between the two groups ($\bar{x}$ ± s)
| Group | Time | HGB (g/L) | PLT (×109/L) | HCT (%) | WBC (×109/L) |
|---|---|---|---|---|---|
| Control (n = 30) | Before treatment | 215.8±36.3 | 251.3±53.8 | 62.4±11.9 | 14.4±2.1 |
| After treatment | 158.7±28.6a | 190.7±31.3a | 28.1±5.4a | 8.3±1.2a | |
| Treatment (n = 30) | Before treatment | 199.6±26.6 | 240.7±50.6 | 58.91±11.00 | 14.2±2.4 |
| After treatment | 139.0±22.4ab | 169.5±39.5ab | 25.6±5.7ab | 6.2±1.1ab |
| Group | Time | D-D (ng/mL) | APTT (s) | PT (s) | FIB (g/L) |
|---|---|---|---|---|---|
| Control (n = 30) | Before treatment | 649.50±99.50 | 42.50±9.50 | 17.86±2.25 | 5.07±1.03 |
| After treatment | 579.24±81.05a | 36.90±7.38a | 14.74±2.08a | 4.12±1.13a | |
| Treatment ( n = 30) | Before treatment | 639.50±109.50 | 42.89±8.74 | 18.25±1.92 | 5.45±1.39 |
| After treatment | 413.59±62.83ab | 31.68±7.07ab | 11.18±2.04ab | 3.42±0.93ab |
Table 7 Comparison of coagulation function indicators between the two groups ($\bar{x}$ ± s)
| Group | Time | D-D (ng/mL) | APTT (s) | PT (s) | FIB (g/L) |
|---|---|---|---|---|---|
| Control (n = 30) | Before treatment | 649.50±99.50 | 42.50±9.50 | 17.86±2.25 | 5.07±1.03 |
| After treatment | 579.24±81.05a | 36.90±7.38a | 14.74±2.08a | 4.12±1.13a | |
| Treatment ( n = 30) | Before treatment | 639.50±109.50 | 42.89±8.74 | 18.25±1.92 | 5.45±1.39 |
| After treatment | 413.59±62.83ab | 31.68±7.07ab | 11.18±2.04ab | 3.42±0.93ab |
| Group | Time | PI3K | AKT1 |
|---|---|---|---|
| Control (n = 30) | Before treatment | 1.002±0.070 | 1.003±0.081 |
| After treatment | 0.756±0.019a | 0.946±0.026a | |
| Treatment ( n = 30) | Before treatment | 1.007±0.122 | 1.003±0.076 |
| After treatment | 0.634±0.017ab | 0.762±0.020ab |
Table 8 Comparison of serum PI3K and AKT1 levels between the two groups ($\bar{x}$ ± s)
| Group | Time | PI3K | AKT1 |
|---|---|---|---|
| Control (n = 30) | Before treatment | 1.002±0.070 | 1.003±0.081 |
| After treatment | 0.756±0.019a | 0.946±0.026a | |
| Treatment ( n = 30) | Before treatment | 1.007±0.122 | 1.003±0.076 |
| After treatment | 0.634±0.017ab | 0.762±0.020ab |
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