Journal of Traditional Chinese Medicine ›› 2024, Vol. 44 ›› Issue (4): 770-783.DOI: 10.19852/j.cnki.jtcm.20240610.002
• Original articles • Previous Articles Next Articles
YANG Qinjun1,2, YIN Dandan3, WANG Hui1, GAO Yating2,4,5, WANG Xinheng1,2, WU Di1,2, TONG Jiabing2,4,5, WANG Chuanbo6(), LI Zegeng2,4,5(
)
Received:
2023-02-22
Accepted:
2023-06-15
Online:
2024-08-15
Published:
2024-06-10
Contact:
Prof. LI Zegeng, Department of Respiratory, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China. Supported by:
YANG Qinjun, YIN Dandan, WANG Hui, GAO Yating, WANG Xinheng, WU Di, TONG Jiabing, WANG Chuanbo, LI Zegeng. Uncovering the action mechanism of Shenqi Tiaoshen formula (参芪调肾方) in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification[J]. Journal of Traditional Chinese Medicine, 2024, 44(4): 770-783.
MOL Id | Name | Degree | BC | CC | TC | Herbs |
---|---|---|---|---|---|---|
MOL000098 | Quercetin | 72 | 0.04720241 | 0.45654835 | 0.12767094 | Renshen (Radix Ginseng), Huangqi (Radix Astragali Mongolici), Shanzhuyu (Fructus Macrocarpiii) |
MOL000006 | Luteolin | 42 | 0.0199764 | 0.41306755 | 0.15736827 | Semen Persicae |
MOL005828 | Nobiletin | 38 | 0.00902303 | 0.401507 | 0.16578947 | Chenpi (Pericarpium Citri Reticulataei) |
MOL000422 | Kaempferol | 30 | 0.01607944 | 0.41398446 | 0.18351648 | Renshen (Radix Ginseng), Huangqi (Radix Astragali Mongolici),Taoren (Semen Persicae) |
MOL005320 | Arachidonic Acid | 29 | 0.02892894 | 0.41398446 | 0.163746 | Renshen (Radix Ginseng), Baijiezi (Semen Sinapis) |
MOL000546 | Diosgenin | 24 | 0.00554195 | 0.39554613 | 0.18587824 | Renshen (Radix Ginseng) |
MOL000358 | Sitosterol | 21 | 0.01046093 | 0.38414006 | 0.16056166 | Chenpi (Pericarpium Citri Reticulataei), Yizhiren (Fructus Alpiniae Oxyphyllae) |
MOL001924 | Paeoniflorin | 21 | 0.00274493 | 0.3569378 | 0.22208884 | Huangqi (Radix Astragali Mongolici) |
MOL008583 | Beta-Sitosterol | 20 | 0.01385171 | 0.40411701 | 0.19143646 | Renshen (Radix Ginseng), Huangqi (Radix Astragali Mongolici), Chenpi (Pericarpium Citri Reticulataei), Taoren ( Semen Persicae) |
MOL007088 | Cryptotanshinone | 19 | 0.00420619 | 0.39139559 | 0.20705957 | Renshen (Radix Ginseng) |
MOL001638 | Phorbol | 19 | 0.00257052 | 0.35899904 | 0.21307301 | Renshen (Radix Ginseng) |
MOL005344 | Ginsenoside Rh2 | 18 | 0.00369042 | 0.38813736 | 0.22120596 | Renshen (Radix Ginseng) |
MOL000392 | Formononetin | 18 | 0.00318226 | 0.38100102 | 0.22580645 | Huangqi (Radix Astragali Mongolici) |
MOL007424 | Artemisinin | 17 | 0.00337229 | 0.37412237 | 0.19847939 | Renshen (Radix Ginseng), Huangqi (Radix Astragali Mongolici) |
MOL005320 | Arachidonate | 17 | 0.00283547 | 0.38493292 | 0.21191085 | Renshen (Radix Ginseng) |
MOL000492 | (+)-Catechin | 16 | 0.00888835 | 0.39139559 | 0.22904412 | Taoren (Semen Persicae), Rougui (Cortex Cinnamomi Cassia) |
MOL002341 | Hesperetin | 15 | 0.0014985 | 0.37714863 | 0.27407407 | Chenpi (Pericarpium Citri Reticulataei) |
MOL000354 | Isorhamnetin | 12 | 0.00370155 | 0.3786802 | 0.26265823 | Huangqi (Radix Astragali Mongolici), Shanzhuyu (Shanzhuyu (Fructus Macrocarpiii) |
MOL000737 | Morin | 11 | 0.0019528 | 0.3786802 | 0.30074328 | Renshen (Radix Ginseng) |
MOL004328 | naringenin | 10 | 9.95E-04 | 0.36532811 | 0.25774648 | Chenpi (Pericarpium Citri Reticulataei) |
Table 1 Key active ingredients and their topological parameters of SQTS in the treatment of COPD
MOL Id | Name | Degree | BC | CC | TC | Herbs |
---|---|---|---|---|---|---|
MOL000098 | Quercetin | 72 | 0.04720241 | 0.45654835 | 0.12767094 | Renshen (Radix Ginseng), Huangqi (Radix Astragali Mongolici), Shanzhuyu (Fructus Macrocarpiii) |
MOL000006 | Luteolin | 42 | 0.0199764 | 0.41306755 | 0.15736827 | Semen Persicae |
MOL005828 | Nobiletin | 38 | 0.00902303 | 0.401507 | 0.16578947 | Chenpi (Pericarpium Citri Reticulataei) |
MOL000422 | Kaempferol | 30 | 0.01607944 | 0.41398446 | 0.18351648 | Renshen (Radix Ginseng), Huangqi (Radix Astragali Mongolici),Taoren (Semen Persicae) |
MOL005320 | Arachidonic Acid | 29 | 0.02892894 | 0.41398446 | 0.163746 | Renshen (Radix Ginseng), Baijiezi (Semen Sinapis) |
MOL000546 | Diosgenin | 24 | 0.00554195 | 0.39554613 | 0.18587824 | Renshen (Radix Ginseng) |
MOL000358 | Sitosterol | 21 | 0.01046093 | 0.38414006 | 0.16056166 | Chenpi (Pericarpium Citri Reticulataei), Yizhiren (Fructus Alpiniae Oxyphyllae) |
MOL001924 | Paeoniflorin | 21 | 0.00274493 | 0.3569378 | 0.22208884 | Huangqi (Radix Astragali Mongolici) |
MOL008583 | Beta-Sitosterol | 20 | 0.01385171 | 0.40411701 | 0.19143646 | Renshen (Radix Ginseng), Huangqi (Radix Astragali Mongolici), Chenpi (Pericarpium Citri Reticulataei), Taoren ( Semen Persicae) |
MOL007088 | Cryptotanshinone | 19 | 0.00420619 | 0.39139559 | 0.20705957 | Renshen (Radix Ginseng) |
MOL001638 | Phorbol | 19 | 0.00257052 | 0.35899904 | 0.21307301 | Renshen (Radix Ginseng) |
MOL005344 | Ginsenoside Rh2 | 18 | 0.00369042 | 0.38813736 | 0.22120596 | Renshen (Radix Ginseng) |
MOL000392 | Formononetin | 18 | 0.00318226 | 0.38100102 | 0.22580645 | Huangqi (Radix Astragali Mongolici) |
MOL007424 | Artemisinin | 17 | 0.00337229 | 0.37412237 | 0.19847939 | Renshen (Radix Ginseng), Huangqi (Radix Astragali Mongolici) |
MOL005320 | Arachidonate | 17 | 0.00283547 | 0.38493292 | 0.21191085 | Renshen (Radix Ginseng) |
MOL000492 | (+)-Catechin | 16 | 0.00888835 | 0.39139559 | 0.22904412 | Taoren (Semen Persicae), Rougui (Cortex Cinnamomi Cassia) |
MOL002341 | Hesperetin | 15 | 0.0014985 | 0.37714863 | 0.27407407 | Chenpi (Pericarpium Citri Reticulataei) |
MOL000354 | Isorhamnetin | 12 | 0.00370155 | 0.3786802 | 0.26265823 | Huangqi (Radix Astragali Mongolici), Shanzhuyu (Shanzhuyu (Fructus Macrocarpiii) |
MOL000737 | Morin | 11 | 0.0019528 | 0.3786802 | 0.30074328 | Renshen (Radix Ginseng) |
MOL004328 | naringenin | 10 | 9.95E-04 | 0.36532811 | 0.25774648 | Chenpi (Pericarpium Citri Reticulataei) |
No. | Genes | MCC Score | Degree | BC | CC | No. | Genes | MCC Score | Degree | BC | CC |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | IL6 | 35984 | 37 | 1372.918 | 0.088484 | 16 | MMP3 | 15176 | 18 | 630.5442 | 0.086957 |
2 | IL-10 | 35462 | 35 | 1809.186 | 0.08755 | 17 | SRC | 14002 | 57 | 5644.229 | 0.090909 |
3 | STAT3 | 31522 | 61 | 5542.987 | 0.090909 | 18 | PTPN11 | 12264 | 47 | 3391.096 | 0.08941 |
4 | FGF2 | 30368 | 23 | 479.668 | 0.087632 | 19 | HGF | 12036 | 26 | 536.7057 | 0.088015 |
5 | MMP9 | 30354 | 20 | 776.8301 | 0.087388 | 20 | EGFR | 11516 | 34 | 1353.179 | 0.089241 |
6 | MMP1 | 30270 | 19 | 1158.218 | 0.086689 | 21 | TGFB1 | 10140 | 17 | 667.4372 | 0.088042 |
7 | VEGFA | 21138 | 33 | 2017.926 | 0.089184 | 22 | HRAS | 8178 | 37 | 1310.815 | 0.088847 |
8 | CREBBP | 20170 | 40 | 6223.5 | 0.089952 | 23 | CTNNB1 | 7684 | 40 | 2212.381 | 0.089552 |
9 | EP300 | 19440 | 46 | 3923.157 | 0.089952 | 24 | TNF | 7342 | 38 | 2301.604 | 0.089156 |
10 | ESR1 | 18860 | 27 | 592.0106 | 0.088959 | 25 | MAPK1 | 7254 | 50 | 4258.772 | 0.090269 |
11 | AKT1 | 18046 | 51 | 5545.408 | 0.090211 | 26 | TP53 | 6782 | 48 | 4923.421 | 0.089638 |
12 | MYC | 16968 | 21 | 437.7729 | 0.088291 | 27 | IL1B | 6708 | 26 | 1063.439 | 0.087878 |
13 | HIF1A | 15504 | 23 | 755.6755 | 0.088374 | 28 | CXCL8 | 6672 | 17 | 281.1361 | 0.087225 |
14 | FOXO3 | 15434 | 24 | 1057.897 | 0.088624 | 29 | ERBB2 | 5858 | 20 | 298.4991 | 0.087687 |
15 | MMP2 | 15200 | 17 | 326.8929226 | 0.086769231 | 30 | JAK21 | 5259 | 20 | 298.4991 | 0.087687 |
Table 2 Hub genes and topological parameters of SQTS in the treatment of COPD
No. | Genes | MCC Score | Degree | BC | CC | No. | Genes | MCC Score | Degree | BC | CC |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | IL6 | 35984 | 37 | 1372.918 | 0.088484 | 16 | MMP3 | 15176 | 18 | 630.5442 | 0.086957 |
2 | IL-10 | 35462 | 35 | 1809.186 | 0.08755 | 17 | SRC | 14002 | 57 | 5644.229 | 0.090909 |
3 | STAT3 | 31522 | 61 | 5542.987 | 0.090909 | 18 | PTPN11 | 12264 | 47 | 3391.096 | 0.08941 |
4 | FGF2 | 30368 | 23 | 479.668 | 0.087632 | 19 | HGF | 12036 | 26 | 536.7057 | 0.088015 |
5 | MMP9 | 30354 | 20 | 776.8301 | 0.087388 | 20 | EGFR | 11516 | 34 | 1353.179 | 0.089241 |
6 | MMP1 | 30270 | 19 | 1158.218 | 0.086689 | 21 | TGFB1 | 10140 | 17 | 667.4372 | 0.088042 |
7 | VEGFA | 21138 | 33 | 2017.926 | 0.089184 | 22 | HRAS | 8178 | 37 | 1310.815 | 0.088847 |
8 | CREBBP | 20170 | 40 | 6223.5 | 0.089952 | 23 | CTNNB1 | 7684 | 40 | 2212.381 | 0.089552 |
9 | EP300 | 19440 | 46 | 3923.157 | 0.089952 | 24 | TNF | 7342 | 38 | 2301.604 | 0.089156 |
10 | ESR1 | 18860 | 27 | 592.0106 | 0.088959 | 25 | MAPK1 | 7254 | 50 | 4258.772 | 0.090269 |
11 | AKT1 | 18046 | 51 | 5545.408 | 0.090211 | 26 | TP53 | 6782 | 48 | 4923.421 | 0.089638 |
12 | MYC | 16968 | 21 | 437.7729 | 0.088291 | 27 | IL1B | 6708 | 26 | 1063.439 | 0.087878 |
13 | HIF1A | 15504 | 23 | 755.6755 | 0.088374 | 28 | CXCL8 | 6672 | 17 | 281.1361 | 0.087225 |
14 | FOXO3 | 15434 | 24 | 1057.897 | 0.088624 | 29 | ERBB2 | 5858 | 20 | 298.4991 | 0.087687 |
15 | MMP2 | 15200 | 17 | 326.8929226 | 0.086769231 | 30 | JAK21 | 5259 | 20 | 298.4991 | 0.087687 |
Figure 1 KEGG enrichment analysis, pathway classification summary, and the key pathway core genes A: KEGG enrichment analysis. B: classification summary of the KEGG-enrichment pathway. C: core genes of the key enrichment pathways. KEGG: Kyoto Encyclopedia of Genes and Genomes.
Figure 2 Effects of body weight, exhaustive swimming test and tail suspension test of rats in each group A: body weight; B: tail suspension struggle times; C: tail suspension immobility time. D: Exhaustive swimming time. CON group: normal saline 1 mL/kg, 21 d; MOD group: normal saline 1 mL/kg, 21 d; SQTS group: SQTS 14.94 g/kg, 21 d. CON: Control group; MOD: model group; SQTS: Shenqi Tiaoshen formula. The data represent the mean ± standard deviation using one-way analysis of variance (n = 6). aP < 0.05 vs model group; bP < 0.05 vs control group.
Figure 3 Changes of lung tissue pathology, lung functions and plasma inflammatory factors of the rats in each group A: HE staining (×200, Scale bar = 100 μm). A1: CON group; A2: MOD group; A3: SQTS group. B: the airway inflammation score; C: the MAN score; D: the MLI score; E: the FVC change; F: the FEV0.1/FVC% change; G: the Cdyn change; H: the RE change; I: plasma levels of IL-13; J: plasma levels of IFN-γ; K: plasma levels of TNF-α; L: plasma levels of interleukin-1β; M: plasma levels of IL-10. CON group: normal saline 1 mL/kg, 21 d; MOD group: normal saline 1 mL/kg, 21 d; SQTS group: SQTS 14.94 g/kg, 21 d. HE: hematoxylin-eosin; CON: control; MOD: model; SQTS: Shenqi Tiaoshen Formula; MAN: mean alveolar numbers score; MLI: mean linear interval; FVC: forced expiratory vital capacity; FEV0.1/FVC%: 0.1 s forced expiratory volume/forced expiratory vital capacity; Cdyn: pulmonary dynamic compliance; RE: resistance of expiration; IL-13: interleukin-13; IFN-γ: interferon-γ; TNF-α: tumor necrosis factor-α; IL-1β: interleukin-1β; IL-10: interleukin-10. The Data represent the mean ± standard deviation using one-way analysis of variance (n = 6). aP < 0.05 vs control group; bP < 0.05 vs model group.
Figure 4 Core proteins of the KEGG enrichment pathway were detected by Western blotting A: Western blotting was performed to analyze the expression of p-PI3K, p-AKT, p-mTOR, HIF-1α, FoXO3α, TLR4, VEGFA, caspase-3 and MMP9 in the lung tissues. B-J: image J software was used to evaluate the protein expression quantitatively. B: relative expression of p-PI3K; C: relative expression of p-AKT; D: relative expression of p-mTOR; E: relative expression of HIF-1α; F: relative expression of FoxO3α; G: relative expression of TLR4; H: relative expression of VEGFA; I: relative expression of caspase-3; J: relative expression of MMP9. CON group: normal saline 1mL/kg, 21 d; MOD group: normal saline 1 mL/kg, 21 d; SQTS group: SQTS 14.94 g/kg, 21 d. CON: control; MOD: model; SQTS: Shenqi Tiaoshen Formula; p-PI3K: phospho-phosphatidylinositol 3 kinase; p-AKT: phospho-protein kinase B; p-mTOR: phospho-mammalian target of rapamycin; HIF-1α: hypoxia-inducible factor-1α; FoXO3α: forkhead box O3α; TLR4: toll-like receptor 4; VEGFA: vascular endothelial growth factor A; MMP9: matrix metalloproteinase-9. The Data represent the mean ± standard deviation using one-way analysis of variance (n = 6). aP < 0.05 vs control group; bP < 0.05 vs model group.
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