Journal of Traditional Chinese Medicine ›› 2024, Vol. 44 ›› Issue (3): 478-488.DOI: 10.19852/j.cnki.jtcm.20240408.003
• Original articles • Previous Articles Next Articles
CHU Mengzhen, WANG Yu, LIN Zhijian, Lyu Jintao, ZHANG Xiaomeng, ZHANG Bing()
Received:
2023-02-22
Accepted:
2023-06-15
Online:
2024-06-15
Published:
2024-04-08
Contact:
ZHANG Bing, School of Chinese Materia Medica, Liangxiang Campus, Beijing University of Chinese Medicine, Beijing 102488, China. Supported by:
CHU Mengzhen, WANG Yu, LIN Zhijian, Lyu Jintao, ZHANG Xiaomeng, ZHANG Bing. Investigation of the active ingredients and mechanism of Shuangling extract in dextran sulfate sodium salt induced ulcerative colitis mice based on network pharmacology and experimental verification[J]. Journal of Traditional Chinese Medicine, 2024, 44(3): 478-488.
ID | Pathway | Gene ratio | P value |
---|---|---|---|
hsa05200 | Pathways in cancer | 29/38 | 4.67E-28 |
hsa05161 | Hepatitis B | 22/38 | 1.37E-26 |
hsa05212 | Pancreatic cancer | 16/38 | 6.01E-22 |
hsa05219 | Bladder cancer | 14/38 | 4.64E-21 |
hsa05205 | Proteoglycans in cancer | 20/38 | 2.97E-20 |
hsa04917 | Prolactin signaling pathway | 15/38 | 2.02E-19 |
hsa05142 | Chagas disease (American trypanosomiasis) | 16/38 | 1.22E-18 |
hsa04668 | TNF signaling pathway | 16/38 | 1.91E-18 |
hsa04620 | Toll-like receptor signaling pathway | 15/38 | 7.87E-17 |
hsa05215 | Prostate cancer | 14/38 | 2.68E-16 |
hsa05213 | Endometrial cancer | 12/38 | 1.09E-15 |
hsa04915 | Estrogen signaling pathway | 14/38 | 1.33E-15 |
hsa04660 | T cell receptor signaling pathway | 14/38 | 1.52E-15 |
hsa05133 | Pertussis | 13/38 | 1.65E-15 |
hsa05160 | Hepatitis C | 15/38 | 2.19E-15 |
hsa04068 | FoxO signaling pathway | 15/38 | 2.42E-15 |
hsa05210 | Colorectal cancer | 12/38 | 8.93E-15 |
hsa05140 | Leishmaniasis | 12/38 | 4.38E-14 |
hsa05220 | Chronic myeloid leukemia | 12/38 | 5.15E-14 |
hsa05223 | Non-small cell lung cancer | 11/38 | 1.62E-13 |
Table 1 KEGG enrichment analysis of related pathways
ID | Pathway | Gene ratio | P value |
---|---|---|---|
hsa05200 | Pathways in cancer | 29/38 | 4.67E-28 |
hsa05161 | Hepatitis B | 22/38 | 1.37E-26 |
hsa05212 | Pancreatic cancer | 16/38 | 6.01E-22 |
hsa05219 | Bladder cancer | 14/38 | 4.64E-21 |
hsa05205 | Proteoglycans in cancer | 20/38 | 2.97E-20 |
hsa04917 | Prolactin signaling pathway | 15/38 | 2.02E-19 |
hsa05142 | Chagas disease (American trypanosomiasis) | 16/38 | 1.22E-18 |
hsa04668 | TNF signaling pathway | 16/38 | 1.91E-18 |
hsa04620 | Toll-like receptor signaling pathway | 15/38 | 7.87E-17 |
hsa05215 | Prostate cancer | 14/38 | 2.68E-16 |
hsa05213 | Endometrial cancer | 12/38 | 1.09E-15 |
hsa04915 | Estrogen signaling pathway | 14/38 | 1.33E-15 |
hsa04660 | T cell receptor signaling pathway | 14/38 | 1.52E-15 |
hsa05133 | Pertussis | 13/38 | 1.65E-15 |
hsa05160 | Hepatitis C | 15/38 | 2.19E-15 |
hsa04068 | FoxO signaling pathway | 15/38 | 2.42E-15 |
hsa05210 | Colorectal cancer | 12/38 | 8.93E-15 |
hsa05140 | Leishmaniasis | 12/38 | 4.38E-14 |
hsa05220 | Chronic myeloid leukemia | 12/38 | 5.15E-14 |
hsa05223 | Non-small cell lung cancer | 11/38 | 1.62E-13 |
Figure 1 Molecular docking research A: structural formula of the main active ingredient. A1: pachymic acid; A2: astilbin; A3: luteolin; A4: lactucopicrin. B: molecular docking diagram of active components of Shuangling extract and key targets. B1-B5: docking results of MK-2206 dihydrochloride, pachymic acid, astilbin, luteolinandlactucopicrin active ingredients with AKT1 target protein. B6-B10: docking results of Corylifol A, pachymic acid, astilbin, luteolinand lactucopicrin active ingredients with IL-6 target protein. IL-6: interleukin-6; AKT1: AKT serine/threonine kinase 1.
Compound | Estimated ΔG (kcal/mol) | |||||
---|---|---|---|---|---|---|
MK-2206 dihydrochloride | Corylifol A | pachymic acid | astilbin | luteolin | lactucopicrin | |
AKT1 | -12.02 | - | -7.41 | -9.59 | -7.09 | -9.87 |
IL-6 | - | -6.65 | -5.39 | -4.2 | -4.95 | -5.45 |
Table 2 Molecular docking results of active Ingredients of Shuangling extract and core targets
Compound | Estimated ΔG (kcal/mol) | |||||
---|---|---|---|---|---|---|
MK-2206 dihydrochloride | Corylifol A | pachymic acid | astilbin | luteolin | lactucopicrin | |
AKT1 | -12.02 | - | -7.41 | -9.59 | -7.09 | -9.87 |
IL-6 | - | -6.65 | -5.39 | -4.2 | -4.95 | -5.45 |
Figure 2 Serum inflammatory cytokine levels and histopathological HE staining A: levels of serum TNF-α; B: levels of serumIL-1β; C: levels of serumIL-6; D: colon tissue pathology HE staining score; E: representative HE stained slices of Shuangling extract in anti-UC (× 400). E1: CON; E2: MOD; E3: MSL; E4: SL-H; E5: SL-L. CON group: normal operation (n = 6); MOD group: 3% DSS without treatment (n = 6); MSL group: 3% DSS rats treated with Mesalazine water solution at a daily dose of 400 mg/kg (n = 6); SL-H group: 3% DSS rats treated with Shuangling extract at a daily dose of 18.34 g/kg for 7 d (n = 6). SL-L group: 3% DSS rats treated with Shuangling extract at a daily dose of 9.17 g/kg for 7 d (n = 6). TNF-α: tumor necrosis factor-α; IL-1β: interleukin-1β; IL-6: interleukin-6; HE: hematoxylin-eosin. CON: control; MOD: model; MSL: mesalazine; SL-H: Shuangling extract high-dose; SL-L: Shuangling extract low-dose; DSS: dextran sulfate solution; UC: ulcerative colitis. The statistical significances were assessed using a one-way analysis of variance followed by Dunnett's test. All results were presented as mean ± standard deviation. aP < 0.01, compared with the CON group; bP < 0.01 and cP < 0.05, compared with the MOD group.
Figure 3 Expression of the CD3 and Foxp3 protein in the colon A: immunohistochemical staining of CD3 protein in mouse colon (× 400). A1: CON; A2: MOD; A3: MSL; A4: SL-H; A5: SL-L. B: immunohistochemical staining of FOXP3 protein in mouse colon (× 400). B1: CON; B2: MOD; B3: MSL; B4: SL-H; B5: SL-L. C: average optical density of CD3 protein in colon tissue of mice in each group; D: average optical density of FOXP3 protein in colon tissue of mice in each group. CON group: normal operation (n = 6); MOD group: 3% DSS without treatment (n = 6); MSL group: 3% DSS rats treated with Mesalazine water solution at a daily dose of 400 mg/kg (n = 6); SL-H group: 3% DSS rats treated with Shuangling extract at a daily dose of 18.34 g/kg for 7 d (n = 6). SL-L group: 3% DSS rats treated with Shuangling extract at a daily dose of 9.17 g/kg for 7 d (n = 6). CD3: cluster of differentiation 3; FOXP3: forkhead box p3; DSS: dextran sulfate solution; UC: ulcerative colitis; CON: control; MOD: model; MSL: mesalazine; SL-H: Shuangling extract high-dose; SL-L: Shuangling extract low-dose; DSS: dextran sulfate solution. The statistical significances were assessed using a one-way analysis of variance followed by Dunnett's test. All results were presented as mean ± standard deviation. aP < 0.05, compared with the CON group; bP < 0.05, compared with the MOD group.
Figure 4 Expression of the AKT and p-AKT protein in the colon A: immunohistochemical staining of AKT protein in mouse colon (× 400). A1: CON; A2: MOD; A3: MSL; A4: SL-H; A5: SL-L; B: immunohistochemical staining of p-AKT protein in mouse colon (× 400). B1: CON; B2: MOD; B3: MSL; B4: SL-H; B5: SL-L; C: average optical density of AKT protein in colon tissue of mice in each group; D: average optical density of p-AKT protein in colon tissue of mice in each group. CON group: normal operation (n = 6); MOD group: 3% DSS without treatment (n = 6); MSL group: 3% DSS rats treated with Mesalazine water solution at a daily dose of 400 mg/kg (n = 6); SL-H group: 3% DSS rats treated with Shuangling extract at a daily dose of 18.34 g/kg for 7 d (n = 6). SL-L group: 3% DSS rats treated with Shuangling extract at a daily dose of 9.17 g/kg for 7 d (n = 6). AKT: AKT serine/threonine kinase; p-AKT: phospho-Akt Serine/threonine kinase; UC: ulcerative colitis; CON: control; MOD: model; MSL: mesalazine; SL-H: Shuangling extract high-dose; SL-L: Shuangling extract low-dose; DSS: dextran sulfate solution. The statistical significances were assessed using a one-way analysis of variance followed by Dunnett's test. All results were presented as mean ± standard deviation. aP < 0.05, cP < 0.01, compared with the CON group; bP < 0.05, dP < 0.01, compared with the MOD group.
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