Fig 1.
The flowchart of technical strategy in current study.
Table 1.
The details about the components with liver injury from urate-lowering Chinese herbs.
Fig 2.
Component-target interaction network and target-pathway network.
Note: (A.) The potential liver injury components urate-lowering Chinese medicine are indicated by blue triangles, the core targets are indicated by red arrows; the direct targets of components and “liver injury” are represented by yellow circles, and the interaction targets of components and “liver injury” are gray. (B.) The pathways are represented by green diamond. The targets are indicated by red arrow; the direct target of the compound and disease are represented by yellow circle, and the interacting proteins are represented by gray circle. To get an initial sense of the biological processes and pathways enriched by putative targets that were relative with liver injury, the functional enrichment analysis was conducted based on DAVID. And the results were classified into several signaling pathways, including pathways in cancer, Epstein-Barr virus infection, Viral carcinogenesis, p38α mitogen-activated protein kinase (MAPK) signaling pathway, the immune system, signal transduction, gene expression, cell cycle, DNA replication, and other processes in Fig 2.
Table 2.
The detail about core target in the component-target interaction network.
Table 3.
The detail of the top 10 pathways in the target-pathway interactive network.
Fig 3.
Distribution and the bubble map of core pathways.
Note: (A.) The vertical axis is the path name and the horizontal axis is the Rich Factor value. The larger the P-value, the higher the channel enrichment; the size of the point indicates the number of enriched targets; the color of the dots is red to green. The value is from small to large. (B.) The yellow to brown pathway lines represent the pathways for important target enrichment, from yellow to brown indicating that the pathway P-values are small to large.
Fig 4.
The structure of 6 compounds with strong binding capacity for p38.
Fig 5.
Docking modes between potential liver damage components and p38.
Note: (A.) 32 potential liver injury components have entered the p38α protein active pocket. (B.) The small molecule of diosgenin penetrated into the active pocket, and mainly forms four hydrogen bonds with the Thr106, Asp168, Asp112 and Ser154 residues on the protein, atotal of 15 residues were bound by hydrophobic interaction on the p38α. (C.) The baicalin small molecule completely penetrated into the active pocket, forming 11 hydrogen bonds with the Arg189, Thr185, Asp150, Lys152, Tyr35 residues on the protein, and the sugar moiety contributed 9 hydrogens. The aglycone part contributed 2 hydrogen bonds, and more hydrophobic interaction with the protein. The hydrophobic interaction residues of the baicalin molecule were 13. (D.) The saikosaponin D molecule completely entered the active pocket, mainly with Glu215 and Thr221 on the protein, Tyr188, Asn114, Lys118, Ala184, Thr185, Lys152 residues form 13 hydrogen bonds, a total of 16 hydrophobic residues. (E.) Tetrandrine small molecules deeped into the active pocket, forming a hydrogen bond with Lys53, and 13 residues formed a hydrophobic effect. (F.) Rutaecarpine completely entered the active pocket and formed a hydrophobic interaction with 10 residues. (G.)Evodiamine completely entered the active pocket, and 11 residues formed a hydrophobic effect.
Table 4.
Binding free energy for 32 components with potential liver injury.
Table 5.
ALT, AST, LDH, ALP enzyme activity of L-02 cells interfered with the representative components with liver injury from urate-lowering Chinese herbs.
Fig 6.
Effect of potential liver injury components on the expression of p38 protein.
Fig 7.
Effects of potential liver injury components on L-02 cells p38 protein expression activity with inhibitor.