A consortium of Hordeum vulgare and gut microbiota against non-alcoholic fatty liver disease via data-driven analysis

Figures & data

Figure 1. The workflow of this study.

Table 1. The Index of available databases for the study.

No.	Databases	Brief description	URL
1	ADMETlab 2.0	A web-based platform to pioneer its pharmacokinetic properties.	https://admetmesh.scbdd.com/
2	admetSAR	A web-based platform to predict the pharmacokinetic properties.	http://lmmd.ecust.edu.cn/admetsar1
3	DisGeNET	Human database to identify targets-diseases correlations.	https://www.disgenet.org/
4	NPASS	A web-based platform to identify targets from herbal plants.	http://bidd.group/NPASS/
5	gutMGene	Microbial informatics platform to identify GM metabolites.	http://bio-annotation.cn/gutmgene
6	OMIM	Human-based database to identify disease-related targets.	https://www.omim.org/
7	Similarity Ensemble Approach (SEA)	Human-based target mining platform on molecules.	https://sea.bkslab.org/
8	String	A web-based tool to identify protein-protein interaction networks.	https://string-db.org/
9	SwissADME	Human-based web server to pioneer drug-like properties.	http://www.swissadme.ch/
10	SwissTargetPrediction (STP)	Human-based web server to explore targets from molecules.	http://www.swisstargetprediction.ch/
11	VENNY 2.1	A web-based tool to draw the Venn diagram.	https://bioinfogp.cnb.csic.es/tools/venny/

Figure 2. (a) The 79 overlapping targets associated with SMs from HV between SEA and STP. (b) The 668 overlapping targets related to SMs from GM between SEA and STP. (c) The number of 66 intersecting targets associated with SMs between 79 targets from (A) and 668 targets from (B). (d) The identification of 31 crux targets between 66 targets from (C) and NAFLD (1836 targets).

Table 2. The number 24 secondary metabolites of HV from NPASS database.

No.	Compounds		Lipinski’s rules				Lipinski’s violations	TPSA(Ų)
		PubChem ID	MW	HBA	HBD	MLog P
			<500	<10	≤5	≤4.15	≤1	<140
1	Salicylic acid	338	138.12	3	2	0.99	0	57.53
2	Gramine	6890	174.24	1	1	1.55	0	19.03
3	Indole-3-acetic acid	802	175.18	2	2	1.11	0	53.09
4	Tyramine	5610	137.18	2	2	1.21	0	46.25
5	Hordenine	68313	165.23	2	1	1.83	0	23.47
6	Dormin	5375200	264.32	4	2	1.44	0	74.60
7	Niacin	938	123.11	3	1	−1.13	0	50.19
8	Abscisic acid	5375199	264.32	4	2	1.44	0	74.60
9	5-Hydroxy-2-nonylchromone	365028	288.38	3	1	2.62	0	50.44
10	S-Methylmethionine sufonium	145692	164.25	3	2	−1.82	0	88.62
11	Tryptanthrin	73549	248.24	3	0	2.22	0	51.96
12	CHEMBL566278	5281113	550.65	8	9	1.34	3	218.44
13	(+)-Abscisic acid	5280896	264.32	4	2	1.44	0	74.60
14	Nonanol	8914	144.25	1	1	2.54	0	20.23
15	Ethylparaben	8434	166.17	3	1	1.64	0	46.53
16	Putrescine hydrochloride	9532	161.07	2	2	0.61	0	52.04
17	Hordenine sulphate	77147	263.31	6	3	0.31	0	106.45
18	Putrescine	1045	88.15	2	2	−0.18	0	52.04
19	Ins(1,2,5,6)P4	14033625	500.08	18	10	−6.17	3	346.74
20	Malonic acid	867	104.06	4	2	−0.99	0	74.60
21	Jasmonic acid	5281166	210.27	3	1	1.68	0	54.37
22	MDL-26752	492218	244.42	4	4	1.03	0	76.10
23	Tryptamine	1150	160.22	1	2	1.26	0	41.81
24	Gibberellin A3	6466	346.37	6	3	1.66	0	104.46

Figure 3. (a) PPI networks (30 nodes and 74 edges). (b) A heatmap of binding energy of SMs on JUN (PDB ID: 1FOS). (c) The molecular conformation on tryptanthrin (PubChem ID: 73549) – JUN (PDB ID: 1FOS) complex. (d) Bubble diagram of 6 signalling pathways associated with occurrence and progression of NAFLD.

Figure 4. GBSTM networks (83 nodes and 93 edges). Green circle: GM; red circle: the Apelin signalling pathway; orange circle: targets; and sky blue circle: SMs.

Figure 5. (a) The molecular conformation on dihydroglycitein (PubChem ID: 101101166) – HDAC5 (PDB ID: 5UWI). (b) The molecular conformation on 1,3-diphenylpropan-2-ol (PubChem ID: 138478) – NOS1 (PDB ID: 4D1N). (c) The molecular conformation on (10[(acetyloxy)methyl]-9-anthryl)methyl acetate (PubChem ID: 613145) -NOS2 (PDB ID: 4NOS).

Figure 6. The chemical structures of four key SMs against NAFLD in the study. (a) tryptanthrin. (b) dihydroglycitein. (c) 1,3-diphenylpropan-2-ol. (d) (10[(acetyloxy)methyl]-9-anthryl)methyl acetate.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.