Journal of Traditional Chinese Medicine ›› 2023, Vol. 43 ›› Issue (2): 386-396.DOI: 10.19852/j.cnki.jtcm.20220617.005
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Yinyanghuo (Herba Epimedii Brevicornus) and its components for chronic obstructive pulmonary disease: preclinical evidence and possible mechanisms
WANG Yide1, GAO Zhen1,2(
)
- 1 Department of Respiration, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi 830000, China
2 Department of Integrative Medicine, Huashan hospital of Fudan University, Shanghai 200040, China
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Received:2021-11-11Accepted:2022-03-09Online:2023-04-15Published:2023-03-14 -
Contact:GAO Zhen, Department of Integrative Medicine, Huashan hospital of Fudan University, Shanghai 200040, China, gaozhen@fudan.edu.cn. Telephone: +86-21-52888301 -
Supported by:National Natural Science Foundation of China: Construction of "Three Dimensional Model of Shenqi deficiency syndrome COPD-Bushenyigi Formulae-biomarker spectrum" of Traditional Chinese Medicine(81760901);Tianshan Innovation Team Plan of Xinjiang: Traditional Chinese Medicine Research Team on Prevention and Treatment of Chronic Obstructive Pulmonary Disease(2017D14013)
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WANG Yide, GAO Zhen. Yinyanghuo (Herba Epimedii Brevicornus) and its components for chronic obstructive pulmonary disease: preclinical evidence and possible mechanisms[J]. Journal of Traditional Chinese Medicine, 2023, 43(2): 386-396.
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Figure 1 Literature screening process COPD: chronic obstructive pulmonary disease.
Figure 1 Literature screening process COPD: chronic obstructive pulmonary disease.
Table 1 Basic characteristics of included literature
| No. | Study | Research type | Gender | Sample size | Model construction method | Intervention | Outcome indicator |
|---|---|---|---|---|---|---|---|
| 1 | Li et al 2013 | In vivo study | Male | 5/5 | CS+LPS | Icariin | HE staining, SOD |
| 2 | Sun et al 2015 | In vivo study; Vitro study | Male | 10/10 | CS+LPS | Icariin | NO, iNOS, CD8, SOD, CD4/CD8 |
| 3 | Sun et al 2014 | In vivo study; Vitro study | Male | 10/10 | CS+LPS; LPS | Icariin | TNF-α, MMP-9, TIMP-1, IL-10 |
| 4 | Xu et al 2013 | Vitro study | / | 6/6 | CSE | Icaritin | ROS, AKT, Nrf2 |
| 5 | Zeng et al 2010 | In vivo study; Vitro study | Male | 6/6 | CS; CSE | Icariin | IL-8, IL-6, TNF-α, NF-kBp65, IL-10 |
| 6 | Hu et al 2020 | Vitro study | / | 6/6 | CSE | Icariin | IL-10, IL-8, TNF-α, MMP9, TIMP1,ROS, NF-kBp65 |
| 7 | Li et al 2014 | In vivo study; Vitro study | Male | 10/10 | CS; CSE | Icariin | TNF-a, IL-8, MMP-9, NF-kBp65 |
| 8 | Wu et al 2014 | Vitro study | / | 3/3 | CSE | Icariin | ROS, AKT, Nrf2 |
Table 1 Basic characteristics of included literature
| No. | Study | Research type | Gender | Sample size | Model construction method | Intervention | Outcome indicator |
|---|---|---|---|---|---|---|---|
| 1 | Li et al 2013 | In vivo study | Male | 5/5 | CS+LPS | Icariin | HE staining, SOD |
| 2 | Sun et al 2015 | In vivo study; Vitro study | Male | 10/10 | CS+LPS | Icariin | NO, iNOS, CD8, SOD, CD4/CD8 |
| 3 | Sun et al 2014 | In vivo study; Vitro study | Male | 10/10 | CS+LPS; LPS | Icariin | TNF-α, MMP-9, TIMP-1, IL-10 |
| 4 | Xu et al 2013 | Vitro study | / | 6/6 | CSE | Icaritin | ROS, AKT, Nrf2 |
| 5 | Zeng et al 2010 | In vivo study; Vitro study | Male | 6/6 | CS; CSE | Icariin | IL-8, IL-6, TNF-α, NF-kBp65, IL-10 |
| 6 | Hu et al 2020 | Vitro study | / | 6/6 | CSE | Icariin | IL-10, IL-8, TNF-α, MMP9, TIMP1,ROS, NF-kBp65 |
| 7 | Li et al 2014 | In vivo study; Vitro study | Male | 10/10 | CS; CSE | Icariin | TNF-a, IL-8, MMP-9, NF-kBp65 |
| 8 | Wu et al 2014 | Vitro study | / | 3/3 | CSE | Icariin | ROS, AKT, Nrf2 |
Table 2 Bias risk assessment results of inclusion research
| No. | Study | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Li et al 2013 | U | U | U | Y | U | U | U | U | Y | Y |
| 2 | Sun et al 2015 | U | U | U | Y | U | U | U | Y | Y | Y |
| 3 | Sun et al 2014 | U | U | U | Y | U | U | U | Y | Y | Y |
| 4 | Xu et al 2013 | U | U | U | U | U | U | U | U | U | U |
| 5 | Zeng et al 2010 | U | U | U | Y | U | U | U | Y | Y | Y |
| 6 | Hu et al 2020 | U | U | U | U | U | U | U | U | U | U |
| 7 | Li et al 2014 | U | U | U | Y | U | U | U | Y | Y | Y |
| 8 | Wu et al 2014 | U | U | U | U | U | U | U | U | U | U |
Table 2 Bias risk assessment results of inclusion research
| No. | Study | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Li et al 2013 | U | U | U | Y | U | U | U | U | Y | Y |
| 2 | Sun et al 2015 | U | U | U | Y | U | U | U | Y | Y | Y |
| 3 | Sun et al 2014 | U | U | U | Y | U | U | U | Y | Y | Y |
| 4 | Xu et al 2013 | U | U | U | U | U | U | U | U | U | U |
| 5 | Zeng et al 2010 | U | U | U | Y | U | U | U | Y | Y | Y |
| 6 | Hu et al 2020 | U | U | U | U | U | U | U | U | U | U |
| 7 | Li et al 2014 | U | U | U | Y | U | U | U | Y | Y | Y |
| 8 | Wu et al 2014 | U | U | U | U | U | U | U | U | U | U |
Table 3 Effect size combination of outcome indicators
| No. | Outcome indicators | Number of experiments | Heterogeneity test | Effects model | Results of Meta-analysis | |||
|---|---|---|---|---|---|---|---|---|
| P | I2 (%) | SMD | 95% CI | P value | ||||
| 1 | SOD | 3 | <0.001 | 88 | Random | 2.45 | (-0.52, 5.42) | 0.110 |
| 2 | ROS | 2 | 0.020 | 80 | Random | -8.60 | (-16.49, -0.70) | 0.030 |
| 3 | NO | 2 | 0.007 | 86 | Random | 0.10 | (-1.69, 1.89) | 0.900 |
| 4 | iNOS | 2 | 0.008 | 86 | Random | -10.18 | (-21.28, 0.92) | 0.070 |
| 5 | TNF-α | 4 | 0.007 | 75 | Random | -3.95 | (-5.93, -1.97) | <0.001 |
| 6 | IL-10 | 3 | 0.004 | 82 | Random | 3.49 | (0.76, 6.22) | 0.010 |
| 7 | IL-8 | 3 | 0.002 | 84 | Random | -12.13 | (-20.53, -3.74) | 0.005 |
| 8 | MMP-9 | 2 | 0.003 | 80 | Random | -7.01 | (-11.77, -2.25) | 0.005 |
| 9 | NF-kBp65 | 3 | 0.005 | 81 | Random | -18.93 | (-31.40, -6.46) | 0.003 |
| 10 | P-AKT | 2 | 0.800 | 0 | Fixed | 6.00 | (3.21, 8.80) | <0.001 |
Table 3 Effect size combination of outcome indicators
| No. | Outcome indicators | Number of experiments | Heterogeneity test | Effects model | Results of Meta-analysis | |||
|---|---|---|---|---|---|---|---|---|
| P | I2 (%) | SMD | 95% CI | P value | ||||
| 1 | SOD | 3 | <0.001 | 88 | Random | 2.45 | (-0.52, 5.42) | 0.110 |
| 2 | ROS | 2 | 0.020 | 80 | Random | -8.60 | (-16.49, -0.70) | 0.030 |
| 3 | NO | 2 | 0.007 | 86 | Random | 0.10 | (-1.69, 1.89) | 0.900 |
| 4 | iNOS | 2 | 0.008 | 86 | Random | -10.18 | (-21.28, 0.92) | 0.070 |
| 5 | TNF-α | 4 | 0.007 | 75 | Random | -3.95 | (-5.93, -1.97) | <0.001 |
| 6 | IL-10 | 3 | 0.004 | 82 | Random | 3.49 | (0.76, 6.22) | 0.010 |
| 7 | IL-8 | 3 | 0.002 | 84 | Random | -12.13 | (-20.53, -3.74) | 0.005 |
| 8 | MMP-9 | 2 | 0.003 | 80 | Random | -7.01 | (-11.77, -2.25) | 0.005 |
| 9 | NF-kBp65 | 3 | 0.005 | 81 | Random | -18.93 | (-31.40, -6.46) | 0.003 |
| 10 | P-AKT | 2 | 0.800 | 0 | Fixed | 6.00 | (3.21, 8.80) | <0.001 |
Table 4 Basic information of active components of Yinyanghuo (Herba Epimedii Brevicornus)
| TCMSC | Active ingredient | OB% | DL |
|---|---|---|---|
| MOL001510 | 24-epicampesterol | 37.58 | 0.71 |
| MOL001645 | Linoleyl acetate | 42.1 | 0.2 |
| MOL001771 | poriferast-5-en-3beta-ol | 36.91 | 0.75 |
| MOL001792 | (2S)-7-hydroxy-2-(4-hydroxyphenyl)chroman-4-one | 32.76 | 0.18 |
| MOL003044 | Chryseriol | 35.85 | 0.27 |
| MOL003542 | 8-Isopentenyl-kaempferol | 38.04 | 0.39 |
| MOL000359 | sitosterol | 36.91 | 0.75 |
| MOL000422 | kaempferol | 41.88 | 0.24 |
| MOL004367 | olivil | 62.23 | 0.41 |
| MOL004373 | Anhydroicaritin | 45.41 | 0.44 |
| MOL004380 | C-Homoerythrinan,1,6-didehydro-3,15,16-trimethoxy-,(3.beta.) | 39.14 | 0.49 |
| MOL004382 | Yinyanghuo A | 56.96 | 0.77 |
| MOL004384 | Yinyanghuo C | 45.67 | 0.5 |
| MOL004386 | Yinyanghuo E | 51.63 | 0.55 |
| MOL004388 | 6-hydroxy-11,12-dimethoxy-2,2-dimethyl-1,8-dioxo-2,3,4,8-tetrahydro-1H-isochromeno[3,4-h]isoquinolin-2-ium | 60.64 | 0.66 |
| MOL004391 | 8-(3-methylbut-2-enyl)-2-phenyl-chromone | 48.54 | 0.25 |
| MOL004394 | Anhydroicaritin-3-O-alpha-L-rhamnoside | 41.58 | 0.61 |
| MOL004396 | 1,2-bis(4-hydroxy-3-methoxyphenyl)propan-1,3-diol | 52.31 | 0.22 |
| MOL004425 | Icariin | 41.58 | 0.61 |
| MOL004427 | Icariside A7 | 31.91 | 0.86 |
| MOL000006 | luteolin | 36.16 | 0.25 |
| MOL000622 | Magnograndiolide | 63.71 | 0.19 |
| MOL000098 | quercetin | 46.43 | 0.28 |
Table 4 Basic information of active components of Yinyanghuo (Herba Epimedii Brevicornus)
| TCMSC | Active ingredient | OB% | DL |
|---|---|---|---|
| MOL001510 | 24-epicampesterol | 37.58 | 0.71 |
| MOL001645 | Linoleyl acetate | 42.1 | 0.2 |
| MOL001771 | poriferast-5-en-3beta-ol | 36.91 | 0.75 |
| MOL001792 | (2S)-7-hydroxy-2-(4-hydroxyphenyl)chroman-4-one | 32.76 | 0.18 |
| MOL003044 | Chryseriol | 35.85 | 0.27 |
| MOL003542 | 8-Isopentenyl-kaempferol | 38.04 | 0.39 |
| MOL000359 | sitosterol | 36.91 | 0.75 |
| MOL000422 | kaempferol | 41.88 | 0.24 |
| MOL004367 | olivil | 62.23 | 0.41 |
| MOL004373 | Anhydroicaritin | 45.41 | 0.44 |
| MOL004380 | C-Homoerythrinan,1,6-didehydro-3,15,16-trimethoxy-,(3.beta.) | 39.14 | 0.49 |
| MOL004382 | Yinyanghuo A | 56.96 | 0.77 |
| MOL004384 | Yinyanghuo C | 45.67 | 0.5 |
| MOL004386 | Yinyanghuo E | 51.63 | 0.55 |
| MOL004388 | 6-hydroxy-11,12-dimethoxy-2,2-dimethyl-1,8-dioxo-2,3,4,8-tetrahydro-1H-isochromeno[3,4-h]isoquinolin-2-ium | 60.64 | 0.66 |
| MOL004391 | 8-(3-methylbut-2-enyl)-2-phenyl-chromone | 48.54 | 0.25 |
| MOL004394 | Anhydroicaritin-3-O-alpha-L-rhamnoside | 41.58 | 0.61 |
| MOL004396 | 1,2-bis(4-hydroxy-3-methoxyphenyl)propan-1,3-diol | 52.31 | 0.22 |
| MOL004425 | Icariin | 41.58 | 0.61 |
| MOL004427 | Icariside A7 | 31.91 | 0.86 |
| MOL000006 | luteolin | 36.16 | 0.25 |
| MOL000622 | Magnograndiolide | 63.71 | 0.19 |
| MOL000098 | quercetin | 46.43 | 0.28 |
Figure 2 Drug-Compound-Target Network of Yinyanghuo (Herba Epimedii Brevicornus) in treating chronic obstructive pulmonary disease COPD: chronic obstructive pulmonary disease.
Figure 2 Drug-Compound-Target Network of Yinyanghuo (Herba Epimedii Brevicornus) in treating chronic obstructive pulmonary disease COPD: chronic obstructive pulmonary disease.
Figure 3 GO function and KEGG enrichment analysis of related targets A: biological processes; B: molecular functions; C: cellular component; D: KEGG pathways. HTLV-1: human T-lymphotropic virus I; TNF-α: tumor necrosis factor-α; PI3K-Akt: phosphatidylin ositol 3-kinase-protein kinase B; KEGG: kyoto encyclopedia of genes and genomes.
Figure 3 GO function and KEGG enrichment analysis of related targets A: biological processes; B: molecular functions; C: cellular component; D: KEGG pathways. HTLV-1: human T-lymphotropic virus I; TNF-α: tumor necrosis factor-α; PI3K-Akt: phosphatidylin ositol 3-kinase-protein kinase B; KEGG: kyoto encyclopedia of genes and genomes.
Figure 4 Schematic diagram of composite structure and interaction between active compound and core target A: 24-epicampesterol and MDM2; B: 24-epicampesterol and MAPK8; C: Icariin and EGFR; D: Kaempferol and IL-6; E: poriferast-5-en-3beta-ol and MDM2; F: Quercetin and MAPK8. MDM2: mousedouble minute 2; MAPK8: mitogen-activated protein kinase 8; EGFR: epidermal growth factor receptor; IL-6: interleukin-6.
Figure 4 Schematic diagram of composite structure and interaction between active compound and core target A: 24-epicampesterol and MDM2; B: 24-epicampesterol and MAPK8; C: Icariin and EGFR; D: Kaempferol and IL-6; E: poriferast-5-en-3beta-ol and MDM2; F: Quercetin and MAPK8. MDM2: mousedouble minute 2; MAPK8: mitogen-activated protein kinase 8; EGFR: epidermal growth factor receptor; IL-6: interleukin-6.
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