Investigating the pharmaceutical substances and action mechanisms of Changmaxifeng granules against tic disorders

Table 1 Chemical composition information of Changmaxifeng granules

No.	tR (minute)	Ion mode	Deviation (ppm)	Fragment; ions	Theoretical value	Molecular formula	Ingredient name	Source
1	0.81	[M-H]- 215.0348	1.86	149.0428	216.0423	C12H8O4	1-furan-2-yl-2-(4-hydroxy-phenyl)ethane-1,2-dione	TM
2	0.82	[M+H]+ 175.1197	1.14	116.0725; 158.0872	174.1117	C6H14N4O2	Arginine	BS
3	0.84	[M-H]- 165.039	-5.45	131.0469	166.0477	C5H10O6	Arabic acid	TM
4	0.85	[M-H]- 195.0492	-6.66	165.0399; 179.0583; 129.0202	195.0583	C6H12O7	Gluconic acid	BS/TM
5	1.03	[M-H]- 133.0139	1.5	71.0096; 115.0034	134.0215	C4H6O5	D-(+)-malic acid	TM
6	1.05	[M-H]- 115.0034	2.61	71.0133	116.011	C4H4O4	Fumaric acid	TM
7	1.37	[M-H]- 128.035	1.56	96.9606	129.0426	C5H7NO3	L-pyroglutamic acid	TM
8	1.49	[M-H]- 191.0206	7.33	111.0066	192.027	C6H8O7	Citric acid	BS/TM
9	1.49	[M-H]- 173.0096	5.78	111.0066; 129.0202	174.0164	C6H6O6	Trans-aconitic acid or its isomer	BS
10	1.71	[M-H]- 188.0566	3.72	128.035; 144.0627; 173.0038	189.0637	C7H11NO5	N-acetylglutamic acid	TM
11	1.72	[M-H]- 343.0668	0.87	191.0206	344.0743	C14H16O10	5-galloylquinic acid	BS
12	1.8	[M-H]- 243.0642	-6.17	107.0534	244.0736	C14H12O4	Gastrodibenzin B/C	TM
13	1.9	[M-H]- 375.1257	-9.06	341.1122; 300.9911	376.1369	C16H24O10	8-debenzoylpaeoniflorin	BS
14	1.95	[M-H]- 493.1178	-3.04	169.0121; 313.0574	494.1272	C19H26O15	6'-O-galloylsucrose or its isomer	BS
15	2.13	[M+H]+ 268.1019	-10.01	119.0341; 136.0614; 268.1090	267.0968	C10H13N5O4	Adenosine	BS
16	2.13	[M+H]+ 136.0614	-6.61	91.0423; 119.0389	135.0545	C5H5N5	AdenIne	TM
17	2.15	[M-H]- 331.0651	-4.23	316.1480; 271.4559	332.0743	C13H16O10	6-O-galloylglucose or its isomer	BS
18	2.28	[M-H]- 493.1178	-3.04	169.0121; 313.0574	494.1272	C19H26O15	6'-O-galloylsucrose or its isomer	BS
19	2.37	[M-H]- 282.0842	1.42	133.0139; 150.0412	283.0917	C10H13N5O5	Guanosine	BS/TM
201	2.46	[M-H]- 169.0121	-9.47	125.0238; 107.0082	170.0215	C7H6O5	Gallic acid	BS/TM
21	2.46	[M-H]- 125.0238	-0.8	81.0333	126.0317	C6H6O3	Maltol	BS
22	2.48	[M-H]- 125.0238	-0.8	107.7866; 95.0097; 77.0962	126.0317	C6H6O3	Pyrogallol	BS
23	2.62	[M-H]- 331.1049	6.04	313.0575	332.1107	C14H20O9	Mudanoside A	BS
241	2.62	[M-H]- 285.0993	6.66	268.0276	286.1053	C13H18O7	Gastrodin	TM
25	2.79	[M-H]- 359.1365	6.4	329.0024; 271.0459	360.142	C16H24O9	1-O-β-D-glucopyranosyl-paeoniflorin	BS
26	3.03	[M-H]- 493.1178	-3.04	169.0121; 313.0574	494.1272	C19H26O15	6'-O-galloylsucrose or its isomer	BS
27	3.14	[M-H]- 164.0698	-8.53	103.0476; 131.0419	165.079	C9H11NO2	L-phenylalanine	TM/ZZM
28	3.15	[M-H]- 331.0651	-4.23	313.0497; 271.0459	332.0743	C13H16O10	6-O-galloylglucose or its isomer	BS
29	3.24	[M-H]- 493.1178	-3.04	169.0121; 313.0574	494.1272	C19H26O15	6'-O-galloylsucrose or its isomer	BS
30	3.27	[M-H]- 313.0574	4.47	113.0234; 137.0263	314.0638	C13H14O9	2-carboxyphenyl-α-D-glucopyranuronic acid	TM
31	3.44	[M-H]- 447.1514	2.46	89.0203; 341.0718; 389.0217	448.1581	C19H28O12	Gastrodin A	TM
32	3.85	[M-H]- 527.1414	2.47	479.0424	528.1479	C23H28O14	Galloyl desbenzoylpaeoniflorin	BS
33	3.98	[M-H]- 589.1218	-1.53	167.0366; 259.0247	590.1305	C24H30O15S	Paeoniflorin E sulfite	BS
34	4	[M+H]+ 385.1481	-4.67	323.103	384.142	C18H24O9	Tenuifoliside D	YZ
35	4.01	[M-H]- 361.1504	1.38	315.0695	362.1577	C16H26O9	6-O-copyranosyl-lactinlide	BS
36	4.24	[M-H]- 343.1396	0.87	310.0282	343.1393	C16H24O8	Mudanpioside F/mudanpioside G	BS
37	4.24	[M-H]- 459.1151	2.61	401.1037	460.1217	C19H24O13	Parishin E/parishin G	TM
38	4.24	[M-H]- 173.0096	5.78	125.0287; 137.0071	174.0164	C6H6O6	Trans-aconitic acid or its isomer	TM
39	4.33	[M-H]- 633.0732	7.58	555.1772	634.0806	C27H22O18	Strictinin	BS
40	4.37	[M-H]- 461.129	-1.08	93.0323; 137.0225	462.1373	C19H26O13	Sibiricose A3	YZ
41	4.41	[M-H]- 705.1734	4.68	543.1223; 259.0247; 121.0279	706.1779	C29H38O18S	Isomaltopaeoniflorinsulfite or its isomer	BS
42	4.48	[M-H]- 451.1218	-4.88	169.0065; 245.0836; 289.0727	452.1319	C21H24O11	Catechin glucoside	BS
43	4.5	[M-H]- 203.0833	5.91	116.0501; 159.0521	204.0899	C11H12N2O2	Tryptophan	SCP
44	4.54	[M-H]- 459.1151	2.61	400.9901	460.1217	C19H24O13	Parishin E/parishin G	TM
45	4.54	[M-H]- 421.0773	0.47	259.0247	422.0849	C19H18O11	Isomangiferin	TM
46	4.55	[M-H]- 543.1121	-9.39	121.0279; 259.0247	544.1251	C23H28O13S	Paeoniflorin sulfite	BS
47	4.56	[M+H]+ 579.1458	-7.77	409.1026	578.1424	C30H26O12	Procyanidin B1/B2	BS
48	4.69	[M-H]- 483.0744	-6.42	125.0189; 151.0002; 169.0121	484.0853	C20H20O14	Paeoniflorin sulfite	BS
49	4.76	[M-H]- 577.1319	-4.68	289.0727	578.1424	C30H26O12	Procyanidin B1/B2	BS
50	4.79	[M-H]- 495.1466	-7.47	465.1419; 137.0225	496.1581	C23H28O12	Oxypaeoniflorin or its isomer	BS
51	4.81	[M+H]+ 414.1312	-5.55	162.0233; 308.0806	413.1257	C17H23N3O7S	Sulfur-(4-hydroxybenzyl)-glutathione	TM
52	4.81	[M+H]+ 576.1881	3.12	320.0902	575.1785	C23H33N3O12S	S-gastrodin-glutathione	TM
53	4.82	[M-H]- 175.0605	-0.57	161.0244	176.0685	C7H12O5	2-Isopropylmalic acid	TM
54	4.92	[M-H]- 635.0884	4.41	169.0121; 313.0574	636.0963	C27H24O18	1,3,6-Tri-O-galloyl-β-D-glucose	BS
55	4.95	[M-H]- 517.1526	-5.99	160.0174; 175.0432; 193.0479	518.1636	C22H30O14	Sibiricose A5	YZ
56	4.97	[M+H]+ 139.0400	3.6	77.0374	138.0317	C7H6O3	Salicylic acid	TM/YZ/SCP
57	4.98	[M+H]+ 291.0884	5.15	247.0267; 263.1024	290.079	C15H14O6	Catechin	BS
58	4.99	[M-H]- 245.0836	8.98	190.026	246.0892	C14H14O4	Peonol	BS
59	5	[M-H]- 289.0727	5.19	123.0444; 205.0483	290.079	C15H14O6	Epicatechin	BS
60	5	[M-H]- 183.0303	5.46	78.0115; 124.0151; 168.0370	184.0372	C8H8O5	Methyl gallate	BS
61	5	[M-H]- 547.1702	7.13	205.0483	548.1741	C23H32O15	Sibiricose A1	YZ
62	5.19	[M-H]- 205.0359	5.36	111.0112	206.0427	C7H10O7	3-Hydroxy-3-(methoxycarbonyl) pentan	TM
63	5.36	[M-H]- 785.0837	0	125.0279	786.0916	C34H26O22	Tellimagrandin I	BS
64	5.36	[M-H]- 889.2623	1.01	85.0282; 111.0066; 780.1116	890.2692	C38H50O24	Parishin V	TM
65	5.39	[M+H]+ 374.1462	-0.53	136.0614	373.1386	C17H19N5O5	N-(4-hydroxypheny) adenosine	TM
66	5.43	[M-H]- 727.2141	7.56	129.0202	728.2164	C32H40O19	Parishin B	TM
67	5.57	[M-H]- 757.2173	-2.38	71.0133; 453.0717	758.2269	C33H42O20	Parishin M	TM
68	5.63	[M-H]- 687.2103	-4.8	635.0635; 165.0502; 121.0279	688.2215	C30H40O18	6'-O-β-D-glucopyranosylalbiflorin	BS
69	5.66	[M+H]+ 342.1699	-1.75	237.0880; 297.0598	341.1627	C20H23NO4	N-Methylhernagine	BS/TM
701	5.71	[M-H]- 479.1568	2.09	525.1579	480.1632	C23H28O11	Albiflorin	BS
71	5.71	[M-H]- 525.158	-5.33	165.0558; 167.0309; 327.1120; 363.1698	526.1686	C24H30O13	Mudanpioside E	BS
72	5.72	[M-H]- 727.2141	7.56	111.0066; 161.0465	728.2164	C32H40O19	Parishin C	TM
73	5.72	[M+H]+ 319.1151	-9.71	301.1047	318.1103	C17H18O6	Evofolin B	SCP
74	5.73	[M+H]+ 197.0822	4.06	151.078; 179.0684	196.0736	C10H12O4	Paeonilactone B	BS
75	5.73	[M+H]+ 133.0648	-3.76	77.0374; 105.0681; 115.0545	132.0575	C9H8O	Cinnamaldehyde	BS/SCP
76	5.98	[M+H]+ 539.1373	-5.19	503.1316	538.1323	C24H26O14	Sibiricaxanthone A	YZ
77	6.00	[M-H]- 285.0404	1.75	257.0396; 268.0276	286.0477	C15H10O6	Kaempferol	BS/TM
78	6.00	[M-H]- 537.1243	-0.19	315.0464; 387.0604	538.1323	C24H26O14	Sibiricaxanthone B	YZ
79	6.08	[M+H]+ 463.1623	4.1	151.0780; 179.0684	462.1526	C23H26O10	Lactiflorin	BS
801	6.09	[M-H]- 479.1568	2.09	77.0387; 121.0329; 165.0607; 327.1063; 449.1483; 959.3233	480.1632	C23H28O11	Paeoniflorin	BS
81	6.09	[M-H]- 121.0279	-9.09	77.0387	122.0368	C7H6O2	4-hydroxybenzaldehyde	TM
82	6.1	[M-H]- 165.0558	3.64	121.0279; 77.0387	166.063	C9H10O3	Paeonol	BS
83	6.16	[M-H]- 431.1373	7.19	327.1041	432.142	C22H24O9	Heptemthoxyflavone	BS
84	6.23	[M-H]- 567.1356	1.06	345.0594; 315.0541; 272.0318	568.1428	C25H28O15	Polygalaxanthone VIII	YZ
85	6.42	[M-H]- 495.1466	-7.47	427.1026; 137.0225	496.1581	C23H28O12	Oxypaeoniflorin or its isomer	BS
86	6.48	[M-H]- 787.104	5.84	169.0121; 456.0666; 617.0786	788.1072	C34H28O22	1,3,4,6-tetragalloylglucose	BS
87	6.55	[M+H]+ 199.0596	-5.02	163.0358; 153.0205	198.0528	C9H10O5	Ethyl gallate	BS
88	6.64	[M-H]- 995.3086	5.43	423.0960; 728.2154	996.3111	C45H56O25	Parishin A	TM
89	6.69	[M-H]- 433.1162	6.23	111.0020; 271.0603; 397.1084	434.1213	C21H22O10	Dihydroxyflavone-glucoside	BS
90	6.73	[M-H]- 300.9986	0.66	271.0603; 245.9800	302.0063	C14H6O8	Ellagic acid	BS
91	6.89	[M+H]+ 271.0762	-0.37	147.0451; 153.0151; 273.0834	272.0685	C15H12O5	Naringenin	BS
92	6.9	[M-H]- 667.1871	-0.45	205.0483; 461.1384	668.1952	C30H36O17	Tenuifoliside B	YZ
93	6.92	[M-H]- 433.1162	6.23	119.0471; 151.0002; 271.0603	434.1213	C21H22O10	Isosalipurposide	BS
94	6.94	[M-H]- 223.0618	5.38	93.0365; 121.0279	224.0685	C11H12O5	Sinapinic acid	TM
95	7.18	[M-H]- 631.1628	-5.55	465.1419; 313.1419; 271.0459; 169.0121	632.1741	C30H32O15	Galloylpaeoniflorin or its isomer	BS
96	7.25	[M-H]- 631.1628	-5.55	465.1419; 313.1419; 271.0459; 169.0121	632.1741	C30H32O15	Galloylpaeoniflorin or its isomer	BS
971	7.44	[M-H]- 939.1152	5.11	769.0880; 617.0786; 447.0591; 169.0121	940.1182	C41H32O26	1,2,3,4,6-pentagalloylglucose	BS
98	7.71	[M-H]- 631.1628	-5.55	465.1419; 313.1419; 271.0459; 169.0121	632.1741	C30H32O15	Galloylpaeoniflorin or its isomer	BS
99	7.81	[M-H]- 611.1589	-3.76	465.1042; 287.0197	612.169	C27H32O16	Polygalaxanthone VII	YZ
1001	7.82	[M-H]- 753.2277	-4.65	205.0518; 223.0675; 367.1056; 529.1638; 547.1773	754.232	C34H42O19	3,6′-disinapoyl sucrose	YZ
101	7.97	[M-H]- 631.1628	-5.55	465.1419; 313.1419; 271.0459; 169.0121	632.1741	C30H32O15	Galloylpaeoniflorin or its isomer	BS
102	8.13	[M-H]- 631.1628	-5.55	465.1419; 313.1419; 271.0459; 169.0121	632.1741	C30H32O15	Galloylpaeoniflorin or its isomer	BS
103	8.2	[M-H]- 723.2156	2.77	631.1628	724.2215	C33H40O18	Arillanin A	YZ
104	8.5	[M+H]+ 481.1678	-6.65	105.0323; 436.1096	480.1632	C23H28O11	Mudanpioside I	BS
105	8.52	[M-H]- 503.1763	-0.4	209.0763; 485.1499	504.1843	C22H32O13	Polygalatenosides E	YZ
106	8.64	[M-H]- 651.1879	-7.06	137.0225; 281.0656; 443.1159	652.2003	C30H36O16	Tenuifoliside-652	YZ
107	8.7	[M-H]- 1453.4358	-6.81	145.0315; 1039.3169; 1119.3817; 1161.3540	1454.4535	C65H82O37	Tenuifoliose Q	YZ
108	8.74	[M-H]- 509.1694	6.87	479.1472; 169.0121; 121.0279	510.1737	C24H30O12	Mudanpioside D	BS
109	8.78	[M+H]+ 481.1678	-6.65	77.0374	480.1632	C23H28O11	Albiflorin R1	BS
110	8.79	[M-H]- 647.1489	8.34	121.0279; 213.0223; 259.0247; 525.0979	648.1513	C30H32O14S	Benzoylpaeoniflorin sulfonate	BS
111	8.81	[M-H]- 283.0826	2.83	255.8088	284.0894	C13H16O7	Benzyl glucoside	BS
112	9.18	[M-H]-783.1761	-1.53	169.0121; 465.1325; 631.1519	784.1851	C37H36O19	3’-6’-D-O-galloylpaeoniflorin	BS
113	9.25	[M-H]- 681.2019	-1.76	179.0349; 281.0656; 443.1159	682.2109	C31H38O17	Tenuifoliside A	YZ
114	9.61	[M+H]+ 271.0609	1.11	95.0152; 207.0684	270.0528	C15H10O5	Galangin	SCP
115	9.65	[M-H]- 269.0438	-4.46	251.0329	270.0528	C15H10O5	Baicalein	BS
116	9.66	[M-H]- 599.1808	7.18	137.0276	600.1843	C30H32O13	Benzoyloxypaeoniflorin	BS
117	9.71	[M-H]- 1525.4702	2.23	1379.4265	1526.4746	C68H86O39	Tenuifoliose F	YZ
118	9.74	[M-H]- 1495.4609	3.14	1161.3540; 1203.3713; 1349.4047	1496.4641	C67H84O38	Tenuifoliose L	YZ
119	9.82	[M-H]- 1253.3766	-0.48	753.2396; 809.2495; 955.3134; 1077.3359	1254.385	C56H70O32	Tenuifoliose T	YZ
120	9.85	[M+H]+ 314.1379	-4.14	93.0645	313.1314	C18H19NO4	N-trans-Feruloyltyramine	TM
121	9.88	[M-H]- 312.1232	-1.28	281.2414	313.1314	C18H19NO4	Feruloyl tyramine	SCP
122	10.01	[M-H]- 447.2253	5.14	59.0121; 89.0244	448.2308	C21H36O10	Geraniol-primeveroside	BS
123	10.12	[M-H]- 767.2444	5.87	223.0672; 237.0764; 529.1638	768.2477	C35H44O19	Tenuifoliside C	YZ
124	10.17	[M-H]- 1223.3766	8.17	145.0315; 307.0751; 955.2988; 1077.3217; 1101.3361	1224.3745	C55H68O31	Tenuifoliose S	YZ
125	10.43	[M-H]- 1295.3929	3.94	997.3134; 1119.3524	1296.3956	C58H72O33	Tenuifoliose C/tenuifoliose E	YZ
126	10.57	[M-H]- 237.0761	-0.84	206.0752; 222.0520	238.0841	C12H14O5	4-hydroxy-3,5-dimethoxylcinnamate	YZ
127	10.67	[M-H]- 1397.621	-1.07	-	1398.6303	C64H102O33	Arillatanoside C	YZ
128	10.79	[M-H]- 445.2051	-5.17	311.0902	446.2152	C21H34O10	Β-pinen-10-yl-β-vicianoside	BS
129	10.83	[M-H]- 1307.3984	8.11	307.0827; 653.1922; 1161.3689	1308.3956	C59H72O33	Tenuifoliose J/tenuifoliose I	YZ
130	10.88	[M-H]- 1265.5903	7.9	425.3125; 455.3217; 499.1701; 585.1967; 1235.5663	1266.5881	C59H94O29	Desacylsenegasaponin B	YZ
131	10.96	[M-H]- 1541.6667	-8.63	425.3125; 1317.3502	1542.6879	C74H110O34	Onjisaponin H	YZ
132	10.98	[M-H]- 1411.6322	-4.25	-	1412.646	C65H104O33	Desacylsenegasaponin III	YZ
133	11.2	[M-H]- 1235.5818	9.79	337.1186; 455.3217; 555.1955	1236.5775	C58H92O28	Arillatanoside A	YZ
134	11.29	[M-H]- 1381.6334	4.2	701.1796; 1157.5767; 1351.6196	1382.6354	C64H102O32	Polygalasaponin XIX	YZ
135	11.36	[M-H]- 711.2166	4.22	694.1769	712.2215	C32H40O18	Telephiose C	SCP
136	11.47	[M-H]- 1249.5913	4.8	425.3125; 455.3217; 1025.5084; 1219.5607	1250.5932	C59H94O28	Onjisaponin Tf	YZ
137	11.5	[M-H]- 1525.6748	3.21	1157.5618; 1351.6196; 1463.7104	1526.6777	C70H110O36	Onjisaponin Te	YZ
138	11.53	[M-H]- 1379.6213	6.81	425.3125; 455.3217; 1235.5817	1380.6198	C64H100O32	Onjisaponin TG	YZ
139	11.54	[M-H]- 1103.5229	-4.08	455.3146	1104.5353	C53H84O24	Polygalasaponin XXVIII	YZ
140	11.55	[M-H]- 1307.3984	8.11	307.0827; 653.1922; 1161.3689	1308.3956	C59H72O33	Tenuifoliose J/tenuifoliose I	YZ
141	11.71	[M-H]- 741.2241	-0.13	179.0583; 684.2599	742.232	C33H42O19	Parishin K	TM
142	11.9	[M-H]- 1367.4008	-5.92	1027.3135; 1191.3721	1368.4167	C61H76O35	Tenuifoliose O	YZ
143	11.91	[M-H]- 1265.3884	8.85	631.1901; 753.2276; 1143.3408; 1223.3461	1266.385	C57H70O32	Tenuifoliose K	YZ
144	11.97	[M-H]- 1349.4048	4.82	1039.3309; 1161.3689; 1203.3713	1350.4061	C61H74O34	Tenuifoliose H	YZ
145	12.18	[M-H]- 583.1800	-2.74	553.1725; 121.0279	584.1894	C30H32O12	Benzoylpaeoniflorin	BS
146	12.18	[M-H]- 629.1896	4.13	121.0279	630.1949	C31H34O14	Mudanpioside B/mudanpioside J	BS
147	12.19	[M-H]- 1379.4103	1.01	347.0917; 1161.3540	1380.4167	C62H76O35	Tenuifoliose A	YZ
148	12.22	[M-H]- 1409.418	-1.06	825.3434; 1069.3090; 1111.3448; 1173.3512; 1191.3871	1410.4273	C63H78O36	Tenuifoliose N	YZ
149	12.22	[M-H]- 1325.3993	0.75	661.2083; 1149.3740; 1203.3866	1326.4061	C59H74O34	Senegose B/C	YZ
150	12.38	[M+H]+ 585.1997	4.27	77.0375; 105.0323	584.1894	C30H32O12	Benzoylalbiflorin	BS
151	12.4	[M-H]- 629.1896	4.13	121.0279	630.1949	C31H34O14	Mudanpioside B/mudanpioside J	BS
152	12.46	[M-H]- 1307.3984	8.11	307.0827; 653.1922; 1161.3689	1308.3956	C59H72O33	Tenuifoliose J/tenuifoliose I	YZ
153	12.51	[M-H]- 327.2147	-7.33	171.1021	328.225	C18H32O5	(12Z, 15Z) -9,10,11-trihydroxy-12,15-octadecadienoic acid	TM
154	12.62	[M+H]+ 303.0843	-8.58	245.0417; 261.0185	302.079	C16H14O6	Onjixanthone I	YZ
155	12.76	[M-H]- 677.355	1.92	629.0362	678.3615	C36H54O12	Sibiricasaponin A	YZ
156	12.83	[M-H]- 679.3682	-1.77	425.3086; 455.3146	680.3772	C36H56O12	Tenuifolin	YZ
157	12.89	[M+H]+ 295.2275	0.68	221.0807	294.2195	C18H30O3	13(S)-HOTrE	BS
158	12.9	[M-H]- 329.2322	-1.82	171.1021; 211.1272; 229.1422	330.2406	C18H34O5	9,12,13-TriHOME	BS
159	13	[M-H]- 1703.7188	-8.22	157.1910; 1479.7279	1704.7407	C80H120O39	Onjisaponin A	YZ
160	13.09	[M-H]- 1631.7034	-5.09	425.3125; 455.3123; 567.1970; 1601.6403	1632.7195	C77H116O37	Onjisaponin O	YZ
161	13.18	[M-H]- 1571.6836	-4.45	567.1865; 1347.6085; 1541.6838	1572.6984	C75H112O35	Onjisaponin B/onjisaponin D	YZ
162	13.23	[M-H]- 1617.6907	-3.34	425.3035; 455.3123; 1393.8030	1618.7039	C76H114O37	Polygalasaponin XLIV	YZ
163	13.26	[M-H]- 1673.7109	-6.81	425.3035; 1617.6730	1674.7301	C79H118O38	Z-polygalasaponin XXXII	YZ
164	13.26	[M+H]+ 347.1114	-4.9	289.0669; 331.1214	346.1053	C18H18O7	1,2,3,6,7-pentamethoxyxanthone	YZ
165	13.33	[M-H]- 1469.6482	3.13	1439.6489	1470.6515	C67H106O35	Polygalasaponin XXXXII	YZ
166	13.34	[M-H]- 1469.6482	-7.28	405.1388	1470.6667	C71H106O32	Onjisaponin Z	YZ
167	13.42	[M-H]- 1485.6475	-4.24	425.3125; 1455.6677	1486.6616	C71H106O33	Onjisaponin E	YZ
168	13.45	[M-H]- 1409.6310	-4.82	425.3125; 455.3217; 1185.6506; 1379.6375	1410.6456	C69H102O30	Onjisaponin Y	YZ
169	13.52	[M-H]- 1587.6880	1.57	155.3035; 583.1805; 1455.6344	1588.6933	C75H112O36	Onjisaponin F	YZ
170	13.52	[M-H]- 1455.6344	-6.05	237.0832; 425.3125; 455.3123; 1425.36638	1456.6511	C70H104O32	Onjisaponin G/onjisaponin J	YZ
171	13.58	[M-H]- 1733.7567	7.67	455.3217; 669.2285	1734.7512	C81H122O40	Onjisaponin S	YZ
172	13.62	[M-H]- 1599.6833	-1.38	1455.6344; 1537.7080	1600.6933	C76H112O36	Onjisaponin Gg/onjisaponin K	YZ
173	13.66	[M-H]- 1425.6309	-1.26	425.3035; 455.3123; 1395.6298; 1426.6205	1426.6405	C69H102O31	Senegasaponin B	YZ
174	13.72	[M-H]- 1323.6033	1.74	425.3035; 455.3217; 1293.5858	1324.6088	C65H96O28	Onjisaponin TH	YZ
175	13.99	[M-H]- 1263.5869	5.54	425.3125; 455.3123; 1233.6174	1264.5877	C63H92O26	Onjisaponin MF	YZ
176	14.31	[M-H]- 317.0649	-3.78	259.0338	318.074	C16H14O7	6,8-dihydroxy-1,2,4-trimethyoxyxanthone	YZ
177	15.66	[M-H]- 455.3146	-3.29	441.2885; 427.2561	456.324	C29H44O4	30-demethylated hederagenin	BS
178	16.3	[M+H]+ 373.2014	-0.27	331.0904	372.1937	C22H28O5	Pyrethrin II	BS
179	16.57	[M-H]- 471.3503	6.15	393.3143	472.3553	C30H48O4	Hederagenin or its isomer	BS
180	16.65	[M+H]+ 520.3367	-6.92	86.0983; 184.0721	519.3325	C26H50NO7P	2-dioleoyl-sn-glycero-3-phosphocholine	TM
181	16.99	[M-H]- 471.3503	6.15	393.3143	472.3553	C30H48O4	23-hydroxybetulinic acid	BS
182	17.29	[M-H]- 233.1523	-8.15	218.8748; 197.9078	234.162	C15H22O2	Acoronene	SCP
183	18.5	[M+H]+ 301.1426	8.63	127.0094; 132.9692	300.1321	C13H20N2O6	5-butyluridine	SCP
184	18.69	[M-H]- 293.1782	9.89	245.8978	294.1831	C17H26O4	6-gingerol	TM
185	20.34	[M+H]+ 297.2404	-8.75	253.1753; 261.0256	296.2351	C18H32O3	13-HODE	TM
186	20.57	[M-H]- 455.3519	-1.32	441.7197; 355.7012	456.3603	C30H48O3	Oleanolic acid or its isomer	BS
187	21.12	[M-H]- 455.3519	-1.32	441.7197; 355.7012	456.3603	C30H48O3	Oleanolic acid or its isomer	BS

¹Identification by comparison with reference material.

TM: Tianma; BS: Baishao; ZZM: Zhenzhumu; YZ: Yuanzhi; SCP: Shichangpu.

Table 2 Blood component information of Changmaxifeng granules

No.	tR/minute	Ion mode	Deviation (ppm)	Fragment ions	Theoretical value	Molecular formula	Ingredient name	Note
1	0.83	[M-H]- 215.0329	-6.98	149.0457	216.0423	C12H8O4	1-Furan-2-yl-2-(4-hydroxy-phenyl)ethane-1,2-dione	P
2	0.85	[M-H]- 195.0516	5.64	165.0439; 179.0590	195.0583	C6H12O7	Gluconic acid	P
3	1.46	[M-H]- 191.0206	7.33	111.0066	192.027	C6H8O7	Citric acid	P
4	1.75	[M-H]-243.0651	-2.47	107.9124	244.0736	C14H12O4	Gastrodibenzin B/C	P
5	1.9	[M-H]- 375.1257	-9.06	341.1122; 300.9911	376.1369	C16H24O10	8-Debenzoylpaeoniflorin	P
6	2.4	[M-H]- 169.0121	9.47	125.0244; 107.1245	170.0215	C7H6O5	Gallic acid	P
7	2.59	[M-H]- 285.0973	-0.35	268.0276	286.1053	C13H18O7	Gastrodin	P
8	2.81	[M-H]- 137.0243	2.92	109.0268	138.0317	C7H6O3	The product of gallic acid takes off two oxygen atoms or its isomer	M
9	2.81	[M-H]- 299.0766	-0.33	175.0088; 283.0656; 285.0088	300.0845	C13H16O8	Gastrodin hydrolysis of pyranose, glucuronidation	M
10	3.01	[M+H]+ 265.0752	2.26	218.0879	264.0668	C10H16O6S	C10H14O3 sulfate	M
11	3.12	[M-H]- 199.0981	5.52	137.0908; 162.8295; 181.0398	200.1049	C10H16O4	Paeonimetabolin II	M
12	3.18	[M-H]- 493.1193	0	169.0118; 313.0659	494.1272	C19H26O15	1'-O-Galloylsucrose	P
13	3.43	[M-H]- 389.1425	-5.91	375.0822	390.1526	C17H26O10	The product of paeoniflorin loses C7H4O and methylation	M
14	3.92	[M-H]- 262.9856	-2.28	125.0146; 168.0027; 183.0244	263.994	C8H8O8S	Methyl gallate sulfate	M
15	3.97	[M-H]- 183.0300	3.82	125.0287; 167.0704	184.0372	C8H8O5	Methyl gallate	M
16	4.34	[M-H]- 461.1273	-4.77	175.0088; 285.0088	462.1373	C19H26O13	Gastrodin glucuronidation	M
17	4.34	[M-H]- 461.1273	-4.77	93.0382; 137.0294	462.1373	C19H26O13	Sibiricose A3	P
18	4.39	[M-H]- 705.1751	7.09	259.0203; 121.0329	706.1779	C29H38O18S	Sulfitation of isomaltosyl paeoniflorin	M
19	4.51	[M-H]- 261.0062	-2.68	171.0163; 215.0649	262.0147	C9H10O7S	3,4-dihydroxyphenylpropionic acid sulfate	M
20	4.54	[M-H]- 459.1132	-1.52	400.9565	460.1217	C19H24O13	Parishin E/Parishin G	P
21	4.56	[M-H]- 543.1189	3.13	121.0281; 259.0273	544.1251	C23H28O13S	Paeoniflorin sulfite	P/M
22	4.74	[M-H]- 345.1527	-6.37	169.1254; 175.0088	346.1628	C16H26O8	C10H18O2-glucuronidation	M
23	4.8	[M-H]- 495.1483	-4.04	137.0345	496.1581	C23H28O12	Oxypaeoniflora	P/M
24	4.87	[M-H]- 223.0607	0.45	164.0299; 176.0824; 208.0458	224.0685	C11H12O5	Sinapinic acid	M
25	4.91	[M-H]- 517.1567	1.93	160.0218; 175.0377; 193.0743	518.1636	C22H30O14	Sibiricose A5	P
26	4.95	[M-H]- 289.071	-0.69	123.0399; 205.0580	290.079	C15H14O6	L-Epicatechin	P
27	5.16	[M-H]- 193.0500	-0.52	133.0153; 151.0411	194.0579	C10H10O4	Ferulic acid	M
28	5.39	[M-H]- 727.2063	-3.16	111.0058	728.2164	C32H40O19	Parishin B	P
29	5.44	[M-H]- 373.0803	8.58	197.0426; 359.0924	374.0849	C15H18O11	Dimethylgallic acid glucuronidation	M
30	5.44	[M-H]- 547.1671	1.46	175.0319; 190.0279; 205.0330; 223.0607	548.1741	C23H32O15	Sibiricose A1	P/M
31	5.67	[M-H]- 727.2062	-3.3	129.0162	728.2164	C32H40O19	Parishin C	P
32	5.68	[M+H]+ 197.0800	-7.1	151	196.0736	C10H12O4	Paeonilactone B	P
33	5.69	[M-H]- 525.1628	3.81	165.0551; 363.1675	526.1686	C24H30O13	Mudanpioside E	P
34	5.7	[M-H]- 479.1568	2.09	525.1579	480.1632	C23H28O11	Albiflorin	P
35	5.72	[M+H]+ 319.1173	-2.82	301.1047	318.1103	C17H18O6	Evofolin B	P
36	5.99	[M-H]- 537.1202	-7.82	315.0473 387.0947	538.1323	C24H26O14	Albiflorin B	P
37	6.03	[M-H]- 449.1454	1.34	77.0388; 197.0390	450.1526	C22H26O10	Paeoniflorin dehydroxymethylene	M
38	6.05	[M-H]- 479.1569	2.3	121.0281; 77.0388	480.1632	C23H28O11	Paeoniflorin	P
39	6.09	[M-H]- 165.0551	-0.61	121.0329	166.063	C9H10O3	Paeonol	P
40	6.16	[M-H]- 276.9997	-7.58	197.0451	278.0096	C9H10O8S	Sulfation of dimethylgallic acid	M
41	6.17	[M-H]- 567.1345	-0.88	315.055	568.1428	C25H28O15	Polygalaxanthone VIII	P
42	6.18	[M+H]+ 569.3103	-7.9	525.3032	568.307	C30H48O8S	Oxidized-23-hydroxybetulinic acid sulfate	M
43	6.5	[M-H]- 197.0451	0.51	151.0840; 167.0474	198.0528	C9H10O5	Dimethylgallic acid	M
44	6.56	[M-H]- 995.3008	-2.41	423.0817; 728.2076	996.3111	C45H56O25	Parishin A	P
45	6.88	[M-H]- 291.0198	7.9	197.0329; 211.0615	292.0253	C10H12O8S	Trimethyl gallate sulfate	M
46	7.15	[M-H]- 631.1572	-1.43	121.0281; 589.0381	632.1659	C30H33O13P	Benzoylpaeoniflorin lost oxygen and oxidative phosphorylation	M
47	7.18	[M-H]- 631.1682	3.01	465.0559; 313.0582; 271.0066; 169.0118	632.1741	C30H32O15	Galloylpaeoniflorin	P
48	7.43	[M-H]- 939.1154	5.32	769.0880; 617.0786; 447.0591; 169.0121	940.1182	C41H32O26	Pentagalloylglucose	P
49	7.91	[M-H]- 753.2276	4.51	205.0518; 223.0541; 529.1585; 547.1569	754.232	C34H42O19	3,6'-Disinapoyl sucrose	P
50	8.09	[M+H]+ 333.0979	1.5	303.0536	332.0896	C17H16O7	Oxypaeoniflorin loses C6H10O6 andketonisation	M
51	8.9	[M-H]- 137.0243	2.92	109.0268	138.0317	C7H6O3	The product of gallic acid takes off two oxygen atoms or its is isomer	M
52	9.12	[M+H]+ 241.1073	-1.24	227.1124	240.0998	C12H16O5	Sinapic acid methylation	M
53	10.52	[M-H]- 237.0764	0.42	103.0904; 163.0302; 193.0258; 222.0247	238.0841	C12H14O5	3,4,5-Trimethoxycinnamic acid	M
54	10.66	[M-H]- 1397.6211	-1	-	1398.6303	C64H102O33	Arillatanoside C	P
55	10.84	[M-H]- 1307.3827	-3.9	307.1561; 1161.3540	1308.3956	C59H72O33	Tenuifoliose J	P
56	10.9	[M-H]- 1265.5747	-4.42	425.3125; 455.3123; 499.1799; 585.2072; 1235.5510	1266.5881	C59H94O29	desacylsenegasaponin B	P
57	11.11	[M-H]- 1367.6119	0.88	425.3035; 687.2446; 1143.5181; 1137.5907	1368.6198	C63H100O32	Onjisaponin F-C12H12O4	M
58	11.23	[M-H]- 1235.5663	-2.75	337.2389; 455.3123; 555.1955	1236.5775	C58H92O28	Arillatanoside A	P
59	11.44	[M-H]- 1103.5256	-1.63	455.3123	1104.5353	C53H84O24	Polygalasaponin XXVIII	P
60	11.5	[M-H]- 1249.5913	4.8	425.3125; 455.3123; 1025.5084	1250.5932	C59H94O28	Onjisaponin Tf	P
61	11.54	[M-H]- 1525.6748	3.21	1157.4280; 1351.5072; 1463.5935	1526.6777	C70H110O36	Onjisaponin Te	P
62	11.56	[M-H]- 1307.3827	-3.9	307.1561; 1161.3540	1308.3956	C59H72O33	Tenuifoliose I	P
63	12.16	[M-H]- 1379.4103	1.01	1161.3391	1380.4167	C62H76O35	Tenuifoliose A	P
64	12.8	[M-H]- 679.3673	-3.09	425.3035; 455.3123	680.3772	C36H56O12	Tenuifolin	P
65	12.9	[M-H]- 329.2345	5.16	171.0906; 211.0615; 229.2078	330.2406	C18H34O5	9,12,13-TriHOME	P
66	13	[M-H]- 1703.7188	-8.22	157.0906; 1479.6775	1704.7407	C80H120O39	Onjisaponin A	P
67	13.1	[M-H]- 1631.7034	-5.09	425.3125; 455.3217; 567.2073; 1601.6753	1632.7195	C77H116O37	Onjisaponin O	P
68	13.21	[M-H]- 1571.6836	-4.45	567.1970; 1347.6245; 1541.6838	1572.6984	C75H112O35	Onjisaponin B	P
69	13.25	[M-H]- 1617.6938	-1.42	425.3035; 455.3123; 1393.6237	1618.7039	C76H114O37	Polygalasaponin XLIV	P
70	13.28	[M-H]- 1673.7109	-6.81	425.3125; 1617.6731	1674.7301	C79H118O38	Z-polygalasaponin XXXII	P
71	13.33	[M-H]- 1469.6482	-7.28	405.1388	1470.6667	C71H106O32	Onjisaponin Z	P
72	13.33	[M-H]- 1469.6482	3.13	1439.566	1470.6515	C67H106O35	Polygalasaponin XXXXII	P
73	13.48	[M-H]- 1409.6310	-4.82	425.3125; 455.3217; 1379.7347	1410.6456	C69H102O30	Onjisaponin Y	P
74	17.29	[M-H]- 233.1522	-8.58	218.8733; 197.8061	234.162	C15H22O2	Acoronene	P
75	19.22	[M-H]- 293.1770	5.8	245.899	294.1831	C17H26O4	6-Gingerol	P

P: Prototypical components ; M: Metabolites.

Table 3 Significantly enriched Gene Ontology biological processes of the target genes

GO term	Subgroup	-log10 (P value)	Count	-log10 (q value)
Modulation of chemical synaptic transmission	Biological process	31.3	47	28.23
Regulation of trans-synaptic signaling	Biological process	31.3	47	28.23
Response to xenobiotic stimulus	Biological process	28.8	44	26.4
Regulation of membrane potential	Biological process	27.1	43	24.8
Signal release	Biological process	23.0	40	21.0
Cellular divalent inorganic cation homeostasis	Biological process	21.6	40	19.7
Cellular calcium ion homeostasis	Biological process	21.9	39	19.9
Calcium ion homeostasis	Biological process	21.5	39	19.6
Calcium ion transport	Biological process	21.0	37	19.2
Muscle system process	Biological process	19.2	36	17.5
Synaptic membrane	Cellular component	31.4	44	29.0
Postsynaptic membrane	Cellular component	29.8	38	27.8
Presynapse	Cellular component	20.3	38	18.7
Neuronal cell body	Cellular component	19.7	37	18.2
Membrane raft	Cellular component	19.2	31	17.8
Membrane microdomain	Cellular component	19.2	31	17.8
Intrinsic component of synaptic membrane	Cellular component	19.6	24	18.1
Distal axon	Cellular component	14.2	24	13.0
Transmembrane transporter complex	Cellular component	11.1	24	10.0
Transporter complex	Cellular component	10.6	24	9.6
Neurotransmitter receptor activity	Molecular function	36.5	33	34.0
Metal ion transmembrane transporter activity	Molecular function	10.9	26	9.3
Ion channel activity	Molecular function	10.6	26	9.1
Channel activity	Molecular function	9.7	26	8.3
Passive transmembrane transporter activity	Molecular function	9.6	26	8.3
Gated channel activity	Molecular function	11.5	24	9.8
Amide binding	Molecular function	10.0	24	8.5
Cation channel activity	Molecular function	10.5	23	9.0
G protein-coupled amine receptor activity	Molecular function	25.0	20	22.8
Peptide binding	Molecular function	8.7	20	7.4

GO: Gene Ontology.

Table 4 Results of Kyoto Encyclopedia of Genes and Genomes enrichment

Description	Gene ratio	Count	-log10 (P value)	-log10 (q value)
Neuroactive ligand-receptor interaction	52/203	52	25.8	23.78
Pathways of neurodegeneration - multiple diseases	43/203	43	13.7	12.38
Alzheimer disease	36/203	36	11.9	10.68
cAMP signaling pathway	32/203	32	15.7	14.18
Calcium signaling pathway	27/203	27	10.8	9.7
Serotonergic synapse	26/203	26	17.9	16.2
MAPK signaling pathway	24/203	24	6.6	6.1
Estrogen signaling pathway	21/203	21	10.9	9.8
Chemical carcinogenesis - reactive oxygen species	21/203	21	7.1	6.5
Ras signaling pathway	20/203	20	6	5.6
Cholinergic synapse	18/203	18	9.8	8.8
Chemokine signaling pathway	18/203	18	6.1	5.7
T cell receptor signaling pathway	17/203	17	9.47	8.5
Neurotrophin signaling pathway	17/203	17	8.5	7.7
Phospholipase D signaling pathway	17/203	17	7	6.5
Thyroid hormone signaling pathway	16/203	16	7.5	6.9
Dopaminergic synapse	16/203	16	7	6.4
Apoptosis	16/203	16	6.8	6.3
C-type lectin receptor signaling pathway	15/203	15	7.6	6.9
Sphingolipid signaling pathway	15/203	15	6.7	6.2
B cell receptor signaling pathway	14/203	14	8	7.3
TNF signaling pathway	14/203	14	6.3	5.8
Endocrine resistance	13/203	13	6.2	5.8
VEGF signaling pathway	12/203	12	7.9	7.2
Gap junction	12/203	12	5.9	5.5
IL-17 signaling pathway	12/203	12	5.6	5.3
Toll-like receptor signaling pathway	12/203	12	5.1	4.9
Fc epsilon RI signaling pathway	11/203	11	6.2	5.8
Longevity regulating pathway - multiple species	10/203	10	5.7	5.34

Table 5 The results of molecular docking of positive control molecules

Receptor-ligand	VEGFA-Ginsenoside Rg3	ESR1-Tamoxifen	AKT1-MK2206	FOS-224	TNF-SPD304	IL-6-LMT-28
Binding energies (kcal/mol)	-9.3	-10.3	-10.0	-8.6	-9.8	-8.8