Journal of Traditional Chinese Medicine ›› 2022, Vol. 42 ›› Issue (4): 586-594.DOI: 10.19852/j.cnki.jtcm.2022.04.004
• Research Articles • Previous Articles Next Articles
Exploring the mechanism of hirudin in the treatment of diabetic kidney disease using network pharmacology combined with molecular docking verification
PANG Xinxin, ZHU Qing, PENG Zining, ZHANG Yage, SHI Xiujie, HAN Jiarui(
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- Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou 450002, China
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Received:2021-04-06Accepted:2021-07-26Online:2022-08-15Published:2022-07-12 -
Contact:HAN Jiarui -
About author:HAN Jiarui, Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou 450002, China. HanJR2018@126.com, Telephone: +86-371-60979837
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Supported by:Natural Science Foundation of Henan Province(202300410256);Research Project of the National TCM Clinical Research Base(2019JDZX2119);Key R & D and Extension Project in Henan Province(202102310505);Key R & D and Extension Project in Henan Province(202102310171)
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PANG Xinxin, ZHU Qing, PENG Zining, ZHANG Yage, SHI Xiujie, HAN Jiarui. Exploring the mechanism of hirudin in the treatment of diabetic kidney disease using network pharmacology combined with molecular docking verification[J]. Journal of Traditional Chinese Medicine, 2022, 42(4): 586-594.
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Figure 1 The network diagram of hirudin-diabetic kidney disease-target
Figure 1 The network diagram of hirudin-diabetic kidney disease-target
Figure 2 PPI relationship diagram of hirudin and DKD Different color lines between nodes represent different interactions. Yellow: protein interaction; black: gene co-expression; light blue: protein homology; dark blue: gene co-evolution; red: gene fusion; green: gene pro-connection. PPI: protein-protein interaction; DKD: diabetic kidney disease.
Figure 2 PPI relationship diagram of hirudin and DKD Different color lines between nodes represent different interactions. Yellow: protein interaction; black: gene co-expression; light blue: protein homology; dark blue: gene co-evolution; red: gene fusion; green: gene pro-connection. PPI: protein-protein interaction; DKD: diabetic kidney disease.
Figure 3 Core target map of hirudin in the treatment of diabetic kidney disease
Figure 3 Core target map of hirudin in the treatment of diabetic kidney disease
Figure 4 Related biological functions of hirudin in the treatment of diabetic kidney disease "count" values represent the number of targets associated with the biological function, and P adjust indicate significance.
Figure 4 Related biological functions of hirudin in the treatment of diabetic kidney disease "count" values represent the number of targets associated with the biological function, and P adjust indicate significance.
Figure 5 Key signaling pathway of hirudin in the treatment of diabetic kidney disease Red indicates the target of hirudin on signaling pathway (the original image is from Kyoto Encyclopedia of Genes and Genomes pathway database).
Figure 5 Key signaling pathway of hirudin in the treatment of diabetic kidney disease Red indicates the target of hirudin on signaling pathway (the original image is from Kyoto Encyclopedia of Genes and Genomes pathway database).
Table 1 Molecular docking data of the core target of diabetic kidney disease treated by hirudin
| No. | Gene symbol | Gene ID | PDB ID | Hydrogen number |
|---|---|---|---|---|
| 1 | Serum albumin | ALB | 6HSC | 3 |
| 2 | RAC-alpha serine/threonine-protein kinase | AKT1 | 1UNQ | 6 |
| 3 | Epidermal growth factor receptor | EGFR | 4LQM | 3 |
| 4 | Proto-oncogene tyrosine-protein kinase Src | SRC | 2IIM | 3 |
| 5 | Catalase | CAT | 1DGB | 6 |
| 6 | Mitogen-activated protein kinase 8 | MAPK8 | 4QTD | 3 |
| 7 | Caspase-3 | CASP3 | 3KJF | 5 |
| 8 | GTPase HRas | HRAS | 4XVR | 2 |
| 9 | Heat shock protein HSP 90-alpha | HSP90AA1 | 4YKZ | 5 |
| 10 | Estrogen receptor | ESR1 | 5AAV | 3 |
Table 1 Molecular docking data of the core target of diabetic kidney disease treated by hirudin
| No. | Gene symbol | Gene ID | PDB ID | Hydrogen number |
|---|---|---|---|---|
| 1 | Serum albumin | ALB | 6HSC | 3 |
| 2 | RAC-alpha serine/threonine-protein kinase | AKT1 | 1UNQ | 6 |
| 3 | Epidermal growth factor receptor | EGFR | 4LQM | 3 |
| 4 | Proto-oncogene tyrosine-protein kinase Src | SRC | 2IIM | 3 |
| 5 | Catalase | CAT | 1DGB | 6 |
| 6 | Mitogen-activated protein kinase 8 | MAPK8 | 4QTD | 3 |
| 7 | Caspase-3 | CASP3 | 3KJF | 5 |
| 8 | GTPase HRas | HRAS | 4XVR | 2 |
| 9 | Heat shock protein HSP 90-alpha | HSP90AA1 | 4YKZ | 5 |
| 10 | Estrogen receptor | ESR1 | 5AAV | 3 |
Figure 6 Optimal binding mode of the main active component of hirudin and the key target protein of diabetic kidney disease a-j of them correspond to the molecular docking diagrams of 1-10 proteins bound to hirudin in Table 1, respectively.
Figure 6 Optimal binding mode of the main active component of hirudin and the key target protein of diabetic kidney disease a-j of them correspond to the molecular docking diagrams of 1-10 proteins bound to hirudin in Table 1, respectively.
Figure 7 Effects of hirudin on protein expression levels of CASP3, AKT1, CAT and HSP90AA1 in renal tissues of DKD rats A: representative images of Western blots. B-E: relative expression of CASP3, AKT1, CAT and HSP90AA1 in renal tissues of DKD rats. CASP3: caspase-3; AKT1: RAC-alpha serine/threonine-protein kinase; CAT: Catalase; HSP90AA1: Heat shock protein HSP 90-alpha;β-actin was applied as control protein. Rats in Control group were given intraperitoneal injection of normal saline; Rats in DKD group were given intraperitoneal injection of 100 mg/kg streptozotocin; Rats in DKD + hirudin group were administered 5 U hirudin by subcutaneous injection. Compared with the normal control group, aP < 0.01, cP < 0.05, and compared with the DKD group, bP < 0.05.
Figure 7 Effects of hirudin on protein expression levels of CASP3, AKT1, CAT and HSP90AA1 in renal tissues of DKD rats A: representative images of Western blots. B-E: relative expression of CASP3, AKT1, CAT and HSP90AA1 in renal tissues of DKD rats. CASP3: caspase-3; AKT1: RAC-alpha serine/threonine-protein kinase; CAT: Catalase; HSP90AA1: Heat shock protein HSP 90-alpha;β-actin was applied as control protein. Rats in Control group were given intraperitoneal injection of normal saline; Rats in DKD group were given intraperitoneal injection of 100 mg/kg streptozotocin; Rats in DKD + hirudin group were administered 5 U hirudin by subcutaneous injection. Compared with the normal control group, aP < 0.01, cP < 0.05, and compared with the DKD group, bP < 0.05.
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