Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease

Table 1 Databases and platform addresses

Database and platform	Address
TCMSP	http://www.tcmspw.com/tcmsp.php
Pubchem	https://pubchem.ncbi.nlmnih.gov
Novopro	https://www.novopro.cn/tools/mol2smiles.html
SwissADME	http://www.swissadme.ch
SwissTargetPrediction	http://www.swisstargetprediction.ch
GeneCards	https://www.genecards.org
OMIM	https://omim.org
DisGeNET	https://www.disgenet.org
VENNY2.1	http://bioinfogp.cnb.csic.es/tools/venny/
GEO	http://www.ncbi.nlm.nih.gov/geo/
STRING	https://string-db.org/
DAVID	https://david.ncifcrf.gov
Bioinformatics	https://www.bioinformatics.com.cn
BioGPS	https://biogps.org
RCSB	https://www.pdbus.org/

GEO: Gene Expression Omnibus; OMIM: Online Mendelian Inheritance in Man database.

Table 2 Active ingredients of the Astragalus-Coptis drug pair

TCM	Serial number	MOL ID	Ingredient	OB (%)	DL
Astragalus membranaceus	HQ1	MOL000379	9,10-dimethoxypterocarpan-3-O-β-D-glucoside	36.74	0.92
	HQ2	MOL000387	Bifendate	31.10	0.67
	HQ3	MOL000442	1,7-Dihydroxy-3,9-dimethoxy pterocarpene	39.05	0.48
	HQ4	MOL000371	3,9-di-O-methylnissolin	53.74	0.48
	HQ5	MOL000380	(6aR,11aR)-9,10-dimethoxy-6a,11a-dihydro-6H-benzofurano[3,2-c]chromen-3-ol	64.26	0.42
	HQ6	MOL000354	Isorhamnetin	49.60	0.31
	HQ7	MOL000378	7-O-methylisomucronulatol	74.69	0.30
	HQ8	MOL000398	Isoflavanone	109.99	0.03
	HQ9	MOL000239	Jaranol	50.83	0.29
	HQ10	MOL000098	Quercetin	46.43	0.28
	HQ11	MOL000438	(3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol	67.67	0.26
	HQ12	MOL000417	Calycosin	47.75	0.24
	HQ13	MOL000422	Kaempferol	41.88	0.24
	HQ14	MOL000392	Formononetin	69.67	0.21
Coptis chinensis Franch	HL1	MOL002903	(R)-Canadine	55.37	0.77
	HL2	MOL001454	Berberine	36.86	0.78
	HL3	MOL002894	Berberrubine	35.74	0.73
	HL4	MOL002904	Berlambine	36.68	0.82
	HL5	MOL001458	Coptisine	30.67	0.86
	HL6	MOL002907	Corchoroside A_qt	104.95	0.78
	HL7	MOL002897	Epiberberine	43.09	0.78
	HL8	MOL000622	Magnograndiolide	63.71	0.19
	HL9	MOL008647	Moupinamide	86.71	0.26
	HL10	MOL013352	Obacunone	43.29	0.77
	HL11	MOL000785	Palmatine	64.60	0.65
	HL12	MOL000098	Quercetin	46.43	0.28
	HL13	MOL002668	Worenine	45.83	0.87

DL: Drug-likeness; MOL: Molecule; OB: Oral bioavailability; TCM: Traditional Chinese medicine.

Table 3 Information on the differential gene expression analysis identified from the Gene Expression Omnibus dataset

Gene symbol	Protein name	Log2FC	P value	Change
PLCE1	Phospholipase C epsilon 1	3.980421	0.00000765	Upregulated
CLIC5	Chloride intracellular channel 5	4.380969	0.00001522	Upregulated
PTPRO	Protein tyrosine phosphatase receptor type O	3.922249	0.00001810	Upregulated
HSPA12A	Heat shock protein family A (Hsp70) member 12A	4.194141	0.00001836	Upregulated
AIF1	Allograft inflammatory Factor 1	3.616273	0.00002007	Upregulated
GMDS	GDP-mannose 4,6-dehydratase	3.900218	0.00002555	Upregulated
SEMA5A	Semaphorin 5A	3.956868	0.00002673	Upregulated
CEP152	Centrosomal protein 152	4.004339	0.00002683	Downregulated
FOXC1	Forkhead Box C1	3.505715	0.00003095	Upregulated
MME	Membrane metalloendopeptidase	3.837958	0.00003666	Upregulated
FGF1	Fibroblast growth Factor 1	3.743398	0.00003695	Upregulated
TNNC1	Troponin C1, slow skeletal and cardiac type	3.602037	0.00004852	Upregulated
CYP2C8	Cytochrome P450 family 2 subfamily C member 8	-3.55671	0.00004895	Downregulated
THBS1	Thrombospondin 1	3.170090	0.00005034	Upregulated
VEGFA	Vascular endothelial growth Factor A	4.261645	0.00005391	Upregulated
LUNAR1	Leukemia-associated noncoding IGF1R activator RNA 1	3.265115	0.00005733	Downregulated
HOXD1	Homeobox D1	3.812893	0.00005999	Upregulated
BMP2	bone morphogenetic protein 2	3.115485	0.00006297	Upregulated
IQGAP2	IQ motif containing GTPase activating protein 2	2.540433	0.00006536	Upregulated
ST3GAL6	ST3 beta-galactoside alpha-2,3-sialyltransferase 6	2.858100	0.00006870	Upregulated
THSD7A	Thrombospondin type 1 domain containing 7A	2.581030	0.00006966	Upregulated
F2R	Coagulation factor II thrombin receptor	2.809148	0.00007121	Upregulated
SLC9A1	Solute carrier family 9 member A1	4.330925	0.00007424	Downregulated
ADORA2B	Adenosine A2b receptor	2.582378	0.00008127	Downregulated
FAM153A	Family with sequence similarity 153 member A	3.774375	0.00009200	Upregulated
ITGB1	Integrin subunit beta 1	3.774328	0.00009284	Downregulated
CDS1	CDP-diacylglycerol synthase 1	2.695287	0.00009577	Upregulated
EGR2	Early growth response 2	3.580285	0.00010401	Downregulated
PLA2R1	Phospholipase A2 receptor 1	3.485108	0.00010718	Upregulated
GAS1	Growth arrest specific 1	3.659052	0.00010882	Upregulated
TYRO3	TYRO3 protein tyrosine kinase	2.854082	0.00011003	Upregulated
LOC101929500	Uncharacterized LOC101929500	2.664931	0.00011229	Upregulated
F3	Coagulation factor III, tissue factor	3.035691	0.00011752	Upregulated
XPNPEP2	X-prolyl aminopeptidase 2	3.454828	0.00013038	Downregulated
FUT6	Fucosyltransferase 6	3.357247	0.00013492	Downregulated
LCN1	Lipocalin 1	2.654097	0.00014868	Downregulated
C1orf21	Chromosome 1 open reading frame 21	2.655885	0.00015593	Upregulated
LOC103344931	Uncharacterized LOC103344931	2.423861	0.00015641	Upregulated
FRY	FRY microtubule binding protein	2.922064	0.00016127	Upregulated
POU2F2	POU class 2 homeobox 2	-2.51972	0.00016162	Downregulated
VEGFA	Vascular endothelial growth Factor A	2.860180	0.00016446	Upregulated
CHRNE	Cholinergic receptor nicotinic epsilon subunit	2.954435	0.00016654	Downregulated
TUBB4A	Tubulin beta 4A class IVa	3.908527	0.00016713	Downregulated
MGAT5	Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase	2.568678	0.00017864	Upregulated
PTPRD	Protein tyrosine phosphatase receptor type D	3.052249	0.00018095	Upregulated
HYAL1	Hyaluronidase 1	-2.217640	0.00018409	Downregulated
DPYSL3	Dihydropyrimidinase like 3	3.782204	0.00018554	Upregulated
UGT2B17	UDP glucuronosyltransferase family 2 member B17	2.604504	0.00018633	Downregulated
PAM	Peptidylglycine alpha-amidating monooxygenase	2.25575	0.00018848	Upregulated
RFC4	Replication Factor C subunit 4	3.094109	0.00020080	Downregulated

Table 4 Core active ingredients of the Astragalus-Coptis drug pair

Serial number	MOL ID	Ingredient	Degree
HQ4	MOL000371	3,9-di-O-methylnissolin	66.0
HQ6	MOL000354	Isorhamnetin	63.0
HQ9	MOL000239	Jaranol	63.0
HQ10, HL12	MOL000098	Quercetin	62.0
HQ13	MOL000422	1,7-Dihydroxy-3,9-dimethoxy pterocarpene	62.0
HQ11	MOL000438	(3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol	58.0
HL11	MOL000785	Palmatine	58.0
HL10	MOL013352	Obacunone	57.0
HL9	MOL008647	Moupinamide	56.0

Table 5 Analysis of topological parameters of key targets

Name	Degree centrality	Betweenness centrality	Closeness centrality	Degree
AKT1	155	6135.22026848002	0.00258397932816537	46
EGFR	127	2630.66165751648	0.00239234449760765	44
TNF	155	6936.3437260436	0.00257069408740359	43
SRC	129	3308.84927642964	0.00240384615384615	43
JUN	117	1696.42973120389	0.00232018561484918	43
CASP3	116	2086.85812276904	0.00233644859813084	43
MAPK3	119	2232.21929446136	0.00233100233100233	43
HSP90AA1	124	3622.00791458381	0.00235849056603773	41
STAT3	123	1881.06728458254	0.00234192037470726	40
ESR1	102	1938.43441498511	0.00224215246636771	38

Table 6 Kyoto Encyclopedia of Genes and Genomes enrichment results

ID	Term	Enrichment	P value	Count
hsa04933	AGE-RAGE signaling pathway in diabetic complications	10.2107004	2.05E-22	31
hsa05417	Lipid and atherosclerosis	6.12795222	3.17E-20	40
hsa04151	PI3K-Akt signaling pathway	4.55917914	3.19E-19	49
hsa04066	HIF-1 signaling pathway	8.15889052	7.92E-17	27
hsa04510	Focal adhesion	5.67892124	1.28E-16	35
hsa04014	Ras signaling pathway	5.16396821	4.42E-16	37
hsa04012	ErbB signaling pathway	8.91256580	3.47E-15	23
hsa04664	Fc epsilon RI signaling pathway	10.1719501	4.44E-15	21
hsa04931	Insulin resistance	7.62447759	7.90E-15	25
hsa04068	FoxO signaling pathway	6.78869516	1.03E-14	27
hsa04010	MAPK signaling pathway	4.25354962	3.49E-14	39
hsa04062	Chemokine signaling pathway	5.31807312	7.06E-14	31
hsa04926	Relaxin signaling pathway	6.38328356	5.15E-13	25
hsa05418	Fluid shear stress and atherosclerosis	5.92405453	2.81E-12	25
hsa04668	TNF signaling pathway	6.64533415	2.32E-12	23
hsa04657	IL-17 signaling pathway	5.95682590	1.70E-08	17
hsa04922	Glucagon signaling pathway	4.30961126	1.88E-05	14
hsa04614	Renin-angiotensin system	10.0245305	4.72E-05	7
hsa04960	Aldosterone-regulated sodium reabsorption	7.12167420	1.01E-04	8
hsa04152	AMPK signaling pathway	4.89982957	1.15E-07	18