Network pharmacology- and molecular docking-based approach for predicting key targets and the potential mechanism of Tripterygium wilfordii Hook F for the treatment of acute lymphoblastic leukaemia

Figures & data

Figure 1. Flow chart of the network pharmacology-based study.

Table 1. Potential effective ingredients of TwHF.

MOLID	MOLName	OB	DL
MOL000296	Hederagenin	36.91	0.75
MOL003182	(+)-Medioresinol di-O-beta-D-glucopyranoside_qt	60.69	0.62
MOL003184	81827-74-9	45.42	0.53
MOL003185	(1R,4aR,10aS)−5-hydroxy-1-(hydroxymethyl)−7-isopropyl-8-methoxy-1,4a-dimethyl-4,9,10,10a-tetrahydro-3H-phenanthren-2-one	48.84	0.38
MOL003187	Triptolide	51.29	0.68
MOL003188	Tripchlorolide	78.72	0.72
MOL003189	WILFORLIDE A	35.66	0.72
MOL003192	Triptonide	67.66	0.7
MOL003196	Tryptophenolide	48.5	0.44
MOL003198	5 alpha-Benzoyl-4 alpha-hydroxy-1 beta,8 alpha-dinicotinoyl-dihydro-agarofuran	35.26	0.72
MOL003199	5,8-Dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3)-coumarin	61.85	0.54
MOL003206	Canin	77.41	0.33
MOL003208	Celafurine	72.94	0.44
MOL003209	Celallocinnine	83.47	0.59
MOL003210	Celapanine	30.18	0.82
MOL003211	Celaxanthin	47.37	0.58
MOL003217	Isoxanthohumol	56.81	0.39
MOL003222	Salazinic acid	36.34	0.76
MOL003224	Tripdiotolnide	56.4	0.67
MOL003225	Hypodiolide A	76.13	0.49
MOL003229	Triptinin B	34.73	0.32
MOL003231	Triptoditerpenic acid B	40.02	0.36
MOL003232	Triptofordin B1	39.55	0.84
MOL003233	Triptofordin B2	107.71	0.76
MOL003234	Triptofordin C2	30.16	0.76
MOL003235	Triptofordin D1	32	0.75
MOL003236	Triptofordin D2	30.38	0.69
MOL003238	Triptofordin F1	33.91	0.6
MOL003239	Triptofordin F2	33.62	0.67
MOL003241	Triptofordin F4	31.37	0.67
MOL003242	Triptofordinine A2	30.78	0.47
MOL003244	Triptonide	68.45	0.68
MOL003245	Triptonoditerpenic acid	42.56	0.39
MOL003248	Triptonoterpene	48.57	0.28
MOL003266	21-Hydroxy-30-norhopan-22-one	34.11	0.77
MOL003267	Wilformine	46.32	0.2
MOL003278	salaspermic acid	32.19	0.63
MOL003279	99694-86-7	75.23	0.66
MOL003280	TRIPTONOLIDE	49.51	0.49
MOL000358	beta-sitosterol	36.91	0.75
MOL000211	Mairin	55.38	0.78
MOL000422	kaempferol	41.88	0.24
MOL000449	Stigmasterol	43.83	0.76
MOL002058	40957-99-1	57.2	0.62
MOL003283	(2R,3R,4S)−4-(4-hydroxy-3-methoxy-phenyl)−7-methoxy-2,3-dimethylol-tetralin-6-ol	66.51	0.39
MOL004443	Zhebeiresinol	58.72	0.19
MOL005828	nobiletin	61.67	0.52
MOL007415	[(2S)−2-[(2S)−2-(benzoylamino)−3-phenylpropanoyl]amino]−3-phenylpropyl] acetate	58.02	0.52
MOL007535	(5S,8S,9S,10R,13R,14S,17R)−17-[(1R,4R)−4-ethyl-1,5-dimethylhexyl]−10,13-dimethyl-2,4,5,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,6-dione	33.12	0.79
MOL009386	3,3'-bis-(3,4-dihydro-4-hydroxy-6-methoxy)−2H-1-benzopyran	52.11	0.54
MOL011169	Peroxyergosterol	44.39	0.82

Figure 2. Venn diagram of drug and disease Targets. The blue circle represents the related target of ALL, and the pink circle represents the related target of TwHF. The intersection of two circles represents the target of TwHF in the treatment of ALL, a total of 43.

Figure 3. Ingredients-target-disease network of TwHF in the treatment of ALL. The green nodes represent the intersection target gene, the yellow nodes represent the active components. The edges represent the interactions between them.

Figure 4. Protein–protein interaction network of TwHF in the treatment of ALL. Nodes represent target genes and proteins, edges represent protein interactions, and the number of connecting lines is directly related to the importance of the target.

Figure 5. Top 30 key target genes of TwHF in the treatment of ALL by protein-protein interaction analysis. Numbers represent protein–protein interactions, and the size of Abscissa values is directly related to the importance of genes.

Figure 6. The 20 most significance of gene ontology analysis of therapy target genes of TwHF on ALL. The ordinate is the functional annotation of GO, and the Abscissa is the number of genes enriched in GO, and the enrichment degree and significance are arranged from top to bottom.

Figure 7. The 20 most significance of pathway enrichment analysis of therapy target genes of TwHF on ALL. The ordinate is the name of KEGG signal pathway, the Abscissa is the proportion of genes, and the enrichment degree and significance are from top to bottom.

Figure 8. Some molecular docking diagram of active ingredient and corresponding target.

Table 2. Molecular docking results of target and active compounds.

	Binding energies (kcal/mol)
Potential effective ingredients	VEGFA	CASP3	RELA	BCL2	CYP1A1	CYP3A4	CYP1B1	MAPK8	ESR1
triptolide	−7.7	−7.0	−8.5	−7.4	—	—	—	−7.7	—
Kaempferol	—	−6.9	−7.2	−7.4	−10.3	−9.9	−10.6	−8.3	—
beta-sitosterol	—	−6.6	—	−8.3	—	—	—	—	—
nobiletin	—	—	—	−6.8	—	—	—	−6.7	−7.1

Figure 9. Triptolide inhibited the proliferation of ALL cells. The cell viability of Jurkat (A), MOLT-4 (B) and Nalm-6 (C) cells treated with different concentrations of triptolide (0, 2, 4, 8, 16, 32 and 64 nM) for 24 and 48 h. *P < 0.05 vs the control group.

Figure 10. Kaempferol inhibited the proliferation of ALL cells. The cell viability of Jurkat (A), MOLT-4 (B) and Nalm-6 (C) cells treated with different concentrations of kaempferol (0, 20, 40, 60, 80, 100, 120 and 140 μM) for 24 and 48 h. *P < 0.05 vs the control group.

Table 3. The IC₅₀ values of Triptolide and Kaempferol on Jurkat, MOLT-4 and Nalm-6 cells for 48 h.

	IC50
Cell lines	Triptolide (nM)	Kaempferol (μM)
Jurkat	12.595 ± 0.659	63.677 ± 4.736
MOLT-4	7.213 ± 0.095	37.693 ± 3.186
Nalm-6	27.863 ± 1.108	68.930 ± 0.594

Data availability statement

The data that support the findings of network pharmacology and molecular docking are available in TCMSP at http://tcmspw.com/tcmsp.php,in Uniport at https://www.uni.protorg/, in GeneCards at https://www.genecards.org/, in OMIM at https://omim.org/, in STRING at https://string-db.org/, in Bioconductor at https:// www.bioconductor.org/, in PubChem at http://pubchem.ncbi.nim.nih.gov/, in PDB at https://www.rcsb.Org/. The data that support the findings of cell viability experiments are available in the figshare repository at https://doi.org/10.6084/m9.figshare.21159064.