Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney, and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

Table 1 Differential metabolites in kidney after Jianpi Gushen Huayu Decoction treatment

No.	Metabolites	Formula	RT (min)	m/z	FC		VIP		Trend		Pathway
					M vs C	J vs M	M vs C	J vs M	M vs C	J vs M
1	15(S)-HpETE	C20H32O4	12.78	335.22	1.14	0.45	0.35	1.71	↑	↓d	Arachidonic acid metabolism
2	16(R)-HETE	C20H32O3	13.91	343.22	1.23	0.28	0.58	1.69	↑	↓d	Arachidonic acid metabolism
3	1-naphthol	C10H8O	8.86	145.06	3.00	0.53	1.51	1.19	↑b	↓c
4	2-isopropylmalate	C7H12O5	1.32	175.06	1.97	2.06	1.61	1.37	↑b	↑c
5	2-methoxyresorcinol	C7H8O3	11.65	141.05	1.21	1.20	1.37	1.34	↑a	↑c
6	3-hydroxy-3-methylglutaric acid	C6H10O5	1.32	161.05	1.68	1.72	1.42	1.33	↑a	↑c
7	3-indoleacrylic acid	C11H9NO2	6.03	186.06	0.52	1.63	1.83	1.38	↓b	↑c
8	4-guanidinobutyric acid	C5H11N3O2	1.35	129.07	0.42	1.67	1.53	1.38	↓b	↑c	Butanoate metabolism
9	4-hydroxybenzoic acid	C7H6O3	5.73	137.02	0.57	3.72	1.39	1.65	↓a	↑d
10	4-oxoretinol	C20H28O2	13.68	299.20	0.47	1.67	1.42	1.37	↓a	↑c
11	5-hydroxyindole-3-acetic acid	C10H9NO3	7.05	192.07	7.50	0.04	1.31	1.44	↑b	↓d	Tryptophan metabolism
12	5-hydroxytryptophan	C11H12N2O3	6.55	221.09	0.23	2.30	1.50	1.65	↓b	↑d	Tryptophan metabolism
13	ACar 20:1	C27H52NO4	13.89	472.40	1.86	0.49	1.67	1.63	↑b	↓d
14	Acetoacetate	C4H6O3	1.44	101.02	2.12	1.55	1.35	1.14	↑a	↑	Arachidonic acid metabolism, synthesis and degradation of ketone bodies, tyrosine metabolism
15	Adrenosterone	C19H24O3	13.34	301.18	1.18	0.67	0.62	1.19	↑	↓c	Steroid hormone biosynthesis
16	Alpha-ketoglutaric acid	C5H6O5	1.25	145.01	0.66	2.60	1.69	1.49	↓b	↑d	Alanine, aspartate and glutamate metabolism, butanoate metabolism
17	Anthranilic acid	C7H7NO2	1.55	138.06	0.71	3.98	1.26	1.83	↓a	↑d	Tryptophan metabolism
18	Asparagine	C4H8N2O3	1.24	131.05	0.41	5.12	1.33	0.91	↓b	↑c	Alanine, aspartate and glutamate metabolism
19	Biotin	C10H16N2O3S	8.15	245.10	0.94	2.00	0.21	1.51	↓	↑d
20	Cholesterol	C27H46O	15.23	387.36	0.84	1.51	0.78	1.29	↓	↑c	Steroid hormone biosynthesis
21	Citraconic acid	C5H6O4	1.33	129.02	1.36	1.74	1.47	1.57	↑a	↑d
22	Citric acid	C6H8O7	6.00	191.02	0.94	1.58	0.19	1.67	↓	↑d	Alanine, aspartate and glutamate metabolism
23	Cnidioside A	C17H20O9	1.55	391.10	2.24	3.36	1.32	1.66	↑a	↑d
24	Corey lactone diol	C8H12O4	1.30	171.07	1.31	1.91	1.23	1.61	↑a	↑d
25	Cortisone	C21H28O5	11.25	361.20	1.85	0.56	1.46	1.44	↑a	↓c	Steroid hormone biosynthesis
26	D-glucosamine 6-phosphate	C6H14NO8P	1.20	258.04	1.02	0.58	0.10	1.37	↑	↓c	Alanine, aspartate and glutamate metabolism
27	D-proline	C5H9NO2	1.54	116.07	0.60	1.97	1.64	1.63	↓b	↑d
28	D-threose	C4H8O4	1.31	101.02	1.70	1.76	1.72	1.53	↑b	↑d
29	Ecgonine	C9H15NO3	9.72	186.11	3.96	0.51	1.73	1.37	↑b	↓c
30	Epitestosterone	C19H28O2	13.23	289.22	1.46	0.32	0.68	1.26	↑	↓c	Steroid hormone biosynthesis
31	Estradiol	C18H24O2	14.93	273.18	0.92	0.62	0.34	1.17	↓	↓c	Steroid hormone biosynthesis
32	Gamma-tocopherol	C28H48O2	13.26	417.37	2.17	0.36	1.38	1.44	↑a	↓d
33	Glutaric acid	C5H8O4	1.43	131.03	1.49	1.93	1.26	1.60	↑a	↑d
34	Guanidineacetic acid	C3H7N3O2	1.31	118.06	0.47	1.17	1.71	0.85	↓b	↑
35	Homovanillic acid	C9H10O4	2.09	181.05	0.52	1.40	1.90	1.20	↓b	↑	Tyrosine metabolism
36	L-aspartic acid	C4H7NO4	1.21	132.03	1.67	0.35	0.50	1.46	↑a	↓d	Alanine, aspartate and glutamate metabolism
37	L-glutamine	C5H10N2O3	1.32	147.08	1.39	0.69	1.47	0.31	↑a	↓d	Alanine, aspartate and glutamate metabolism
38	L-histidine	C6H9N3O2	1.65	154.06	0.60	1.06	1.47	0.30	↓a	↑	Histidine metabolism
39	L-kynurenine	C10H12N2O3	8.39	209.09	0.17	3.30	1.60	1.06	↓b	↑a	Tryptophan metabolism
40	L-thyroxine	C15H11I4NO4	11.98	775.68	0.59	0.79	1.36	0.72	↓a	↓	Tyrosine metabolism
41	L-tryptophan	C11H12N2O2	6.70	205.10	0.25	3.24	1.55	1.06	↓b	↑d	Tryptophan metabolism
42	L-tyrosine	C9H11NO3	1.98	180.07	0.44	1.03	1.95	0.36	↓b	↑	Tyrosine metabolism
43	Metanephrine	C10H15NO3	8.92	196.10	3.35	0.21	1.25	1.30	↑a	↓c	Tyrosine metabolism
44	Methionine	C5H11NO2S	1.43	150.06	0.17	3.10	1.67	1.62	↓b	↑d	Cysteine and methionine metabolism
45	N-acetylaspartic acid	C6H9NO5	1.21	128.04	1.00	0.54	0.07	1.53	↑	↓d	Alanine, aspartate and glutamate metabolism
46	N-acetylserotonin	C12H14N2O2	7.25	219.11	0.29	2.46	1.23	1.44	↓a	↑d	Tryptophan metabolism
47	Oxoadipic acid	C6H8O5	1.20	159.03	0.54	2.37	1.35	1.52	↓b	↑d	Tryptophan metabolism
48	PC (16:0/16:0)	C40H80NO8P	16.96	734.57	0.67	1.64	1.18	1.85	↓	↑d	Arachidonic acid metabolism, glycerophospholipid metabolism
49	Prostaglandin D2	C20H32O5	11.09	351.22	0.87	0.46	0.36	1.26	↓	↓c	Arachidonic acid metabolism
50	Urocanic acid	C6H6N2O2	1.76	139.05	1.61	1.05	1.23	0.54	↑a	↑	Histidine metabolism
51	Vitamin B2	C17H20N4O6	7.92	377.15	0.17	4.09	1.48	1.69	↓b	↑d	Riboflavin metabolism

^aP < 0.05 as compared to the control group.

^bP < 0.01 as compared to the control group.

^cP < 0.05 as compared to the model group.

^dP < 0.01 as compared to the model group.

C: Control group; M: Model group, J: High-dose Jianpi Gushen Huayu Decoction group, n = 6 per group; RT: Retention time; VIP: Variable importance for the projection; FC: Fold change.