Supplementary Information
A network-based method for mechanistic investigation of Shexiang Baoxin Pill's treatment of cardiovascular diseases Hai-Yang Fang1§, Hua-Wu Zeng2§, Li-Mei Lin1, Xing Chen1, Xiao-Na Shen1, Peng Fu2, Chao Lv2, Qun Liu2, Run-Hui Liu*2, Wei-Dong Zhang*2 and Jing Zhao*1,2
1
Department of Mathematics, Logistical Engineering University, Chongqing, China
2
Department of Natural Medicinal Chemistry, Second Military Medical University, Shanghai, China
§
These authors contributed equally to this work
*
Corresponding
author:
Jing
Zhao:
[email protected],
Wei-dong
Zhang:
[email protected], and Run-hui Liu:
[email protected]
Contents Table S1. Genes associated with CVD Table S2. Chemical compounds of SBP Table S3. SBP’s target proteins Table S4. SBP’s plasma absorbed compounds and their targets Table S5. Significantly expressed genes and corresponding fold change values Table S6. Content of the 26 bioactive compounds in the SBPpc solution Table S7. The 63 experimentally validated CVD pathways regulated by both SBPac and SBPpc
Table S1 Genes associated with CVD
Entrez ID 26298 338 197 114805 3553 390174 4837 7980
GENE Symbol EHF APOB AHSG GALNT13 IL1B OR9G1 NNMT TFPI2
441911 5465 283189 2646 5139 339479 9201 57698 118 51083 56259 6364 151 1907 1524 5743 4023 57761 2696 5791 2161 54873 10911 2688 84059 3479 1401 9619 6696 9955 10221 2876 8858 120406 3992 3569 3784 116519 2894 4313 337 7450 221692
OR10J3 PPARA OR9G4 GCKR PDE3A FAM5C DCLK1 KIAA1598 ADD1 GAL CTNNBL1 CCL20 ADRA2B EDN2 CX3CR1 PTGS2 LPL TRIB3 GIPR PTPRE F12 PALMD UTS2 GH1 GPR98 IGF1 CRP ABCG1 SPP1 HS3ST3A1 TRIB1 GPX1 PROZ FAM55B FADS1 IL6 KCNQ1 APOA5 GRID1 MMP2 APOA4 VWF PHACTR1
2695 11132 91137 63826 7124 7054 22926 3484 54769 285195 2243 2099 348 9365 153241 10891 6462 10257 2056 4288 3557 81833 1435 3673 4153 26059 6774 22843 585 1559 167465 5169 183 4852 4056 128821 5950 5739 1002 7412 2852 1813 3600
GIP CAPN10 SLC25A46 SRR TNF TH ATF6 IGFBP1 DIRAS2 SLC9A9 FGA ESR1 APOE KL CEP120 PPARGC1A SHBG ABCC4 EPO MKI67 IL1RN SPACA1 CSF1 ITGA2 MBL2 ERC2 STAT3 PPM1E BBS4 CYP2C9 ZNF366 ENPP3 AGT NPY LTC4S CST9L RBP4 PTGIR CDH4 VCAM1 GPER DRD2 IL15
9575 814 5328 128822 129684 60412 4524 2159 9415 6144 1113 5480 7048 23310 4016 4878 3667 79001 1234 2212 2897 255520 6403 4881 53942 2152 5891 5144 57580 2786 23118 2784 1012 152330 1278 3039 91074 5142 376497 1585 3576 8091 7351
CLOCK CAMK4 PLAU CST9 CNTNAP5 EXOC4 MTHFR F10 FADS2 RPL21 CHGA PPIC TGFBR2 NCAPD3 LOXL1 NPPA IRS1 VKORC1 CCR5 FCGR2A GRIK1 ELMOD2 SELP NPR1 CNTN5 F3 MOK PDE4D PREX1 GNG4 TAB2 GNB3 CDH13 CNTN4 COL1A2 HBA1 ANKRD30A PDE4B SLC27A1 CYP11B2 IL8 HMGA2 UCP2
284040 5627 1952 222553 104 6347 5468 51741 57531 55720 2100 23345 3630 6720 54332 4208 6401 3123 185 1557 7040 3586 9745 55247 25924 213 26047 154 2138 1404 6331 127385 2168 57863 79068 1805 325 3084 2244 23671 3240 9370 257194
CDRT4 PROS1 CELSR2 SLC35F1 ADARB1 CCL2 PPARG WWOX HACE1 TSR1 ESR2 SYNE1 INS SREBF1 GDAP1 MEF2C SELE HLA-DRB1 AGTR1 CYP2C19 TGFB1 IL10 ZNF536 NEIL3 MYRIP ALB CNTNAP2 ADRB2 EYA1 HAPLN1 SCN5A OR10J5 FABP1 CADM3 FTO DPT APCS NRG1 FGB TMEFF2 HP ADIPOQ NEGR1
7881 177 56606 54914 7839 133 22795 8792 3297 3952 10060 948 23263 1471 4018 9771 55703 2200 4846 160777 3690 23293 7143 7421 4982 9388 5327 153 2952 5314 9962 54212 84236 345 3753 7391 5350 2878 6262 6558 10516 875 387119
KCNAB1 AGER SLC2A9 KIAA1797 LSL ADM NID2 TNFRSF11A HSF1 LEP ABCC9 CD36 MCF2L CST3 LPA RAPGEF5 POLR3B FBN1 NOS3 CCDC60 ITGB3 SMG6 TNR VDR TNFRSF11B LIPG PLAT ADRB1 GSTT1 PKHD1 SLC23A2 SNTG1 RHBDD1 APOC3 KCNE1 USF1 PLN GPX3 RYR2 SLC12A2 FBLN5 CBS CEP85L
58191 7099 26476 5054 219493 2155 7941 2266 8600 64241 9312 1906 5444 3762 84722 6532 9353 3383 3077 3329 6288 79991 2053 3075 6638 9631 726 341 5742 2169 2205 54504 3757 79698 55668 27303 5445 137492 5992 1573 192343 7486 1071
CXCL16 TLR4 OR10J1 SERPINE1 OR5AR1 F7 PLA2G7 FGG TNFSF11 ABCG8 KCNB2 EDN1 PON1 KCNJ5 PSRC1 SLC6A4 SLIT2 ICAM1 HFE HSPD1 SAA1 OBFC1 EPHX2 CFH SNRPN NUP155 CAPN5 APOC1 PTGS1 FABP2 FCER1A CPVL KCNH2 ZMAT4 C14orf118 RBMS3 PON2 VPS37A RFX4 CYP2J2 NEWENTRY WRN CETP
3481 164781 7408 5781 7139 1047 9948 161357 7422 131096 3570 64410 10217 1356 4314 54433 1636 335 11107 10082 1277 4318 6843 3606 9722 255738 1520 9905 338675 10003 6894 3949 6649 56729 4879
IGF2 WDR69 VASP PTPN11 TNNT2 CLGN WDR1 MDGA2 VEGFA KCNH8 IL6R KLHL25 CTDSPL CP MMP3 GAR1 ACE APOA1 PRDM5 GPC6 COL1A1 MMP9 VAMP1 IL18 NOS1AP PCSK9 CTSS SGSM2 OR5AP2 NAALAD2 TARBP1 LDLR SOD3 RETN NPPB
Table S2. SBP’s medicinal materials and chemical compounds
Medicinal material Moschus
Chemical compound Muscone Normuscone Muscopyridine Muscol
Total gingenoside ginseng root
Bufonis Venenum
Muscopyran Hydroxymuscopyridine A Hydroxymuscopyridine B 3-Methylcyclotridecan-1-One Cyclotetradecanone Cholest-4-En-3-One Cholesterol Testosterone Estradiol 5 Alpha-Androstan-3,17-Dione Panaxadiol Panaxatrio1 Oleanolic Acid Ginsenoside Fc Ginsenoside Ra1 Ginsenoside Ra2 Ginsenoside Ra3 Ginsenoside Rb1 Ginsenoside Rb2(20-[(6-O-Alpha-L-Arabinopyranosyl-Beta-D-Glucop yranosyl)Oxy]-12Beta-Hydroxydammar-24-En-3Beta-Yl 2-O-Beta-D-Glucopyranosyl-Beta-D-Glucopyranoside) Ginsenoside Rb3(Dammarane,B-D-Glucopyranoside Deriv) Ginsenoside Rd Ginsenoside Rc Ginsenoside Re Ginsenoside Rf(Dammarane,B-D-Glucopyranoside Deriv) Ginsenoside Rg1 Ginsenoside Rg2 Ginsenoside Rg3 Ginsenoside Rh1 Ginsenoside Rh2 Ginsenoside Ro Ginsenoside Rs1 Ginsenoside Rs2 Notoginsenoside R1 Notoginsenoside R2 Notoginsenoside Fa Quinquenoside R1 Cinobufagin 3-Acetate Resibufogenin Resibufagin
Bovis Calculus Artifactus
Cinobufagin 1-Hydroxy-Cinobufagin Gamabufotalin(Gamabufogenin) Arenobufagin Bufalin 1Β-Hydroxybufalin Bufotalin Bufarenogin Ψ-Bufarenogin(Psi-Bufarenogin) Desacetylbufotalin Telocinobufagin Cinobufotalin 19-Oxo-Desacetyl-Cinobufotalin Resibufogenol Cinobufaginol 19-Oxo-Cinobufotalin Marinobufagenin Desacetyl-Cinobufagin Desacetylcinobufaginol Bufotalidin(Hellebrigenin) Bufotalinin Marinobufagin Nicotinamide Butanoic Acid Bufoserotonins A Bufoserotonins B Bufoserotonins C 2-Piperidinecarboxylic Acid 6-Oxo-Methylester Adenine Uracil 5-Hydroxyindoleacetic Acid (5-Hiaa)(5-Hydroxyindole-3-Acetic Acid) Bufothionine Ursodeoxycholic Acid Cholic Acid Deoxycholic Acid Chenodeoxycholic Acid Hyodeoxycholic Acid Taurocholic Acid Glycocholic Acid Cholesterol Bilirubin
Styrax
Cinnamomi Cortex
Benzyl Benzoate(Ascabin) Oleanonic Acid 3-Epioleanolic Acid Pimaric Acid Isopimaric Acid Dehydroabietic Acid Abietatriene-3Β-Ol Methyl 4-Hydroxycinnamate(Methyl P-Couma) Vanillin Vanillic Acid 5-Hydroxymethyl-2-Furaldehyde Cinnamyl Acetate Benzyl Cinnamate Alpha-Pinene Beta-Pinene Myrcene Camphene Limonene L, 8-Cineole P-Cymene Terpinolene Linalool 4-Terpineol A-Terpineol Cinnamaldehyde 4-Ethyphenol 2-Ethyphenol 3-Ethyphenol Allylphenol N-Propyl Cinnamate Β-Phenylpropionic Acid L-Benzoyl-3-Phenylpropyne Benzoic Acid Palmitic Acid Linoleic Acid Dihydrocoumarone Epoxycinnamyl Cinnamate Cis-Cinnamic Acid Cis-Cinnamylcinnamate Cinnamaldehyde Cinnamyl Acetate Ethylcinnamate Benzyl Benzoate
Borneolum Syntheticum
Benzaldehyde Coumarin Β-Cadinene Calamenene Β-Elemane Protocatechuic Acid Transcinnamic Acid 3'-○-Methyl-(-)-Epicatechin 5,3'-Di-O-Methylate-(-)-Epicatechin 5,7,3'-Tri-O-Methylate-(-)-Epicatechin (4'-○-Methyl-(+)-Catechin) (7,4'-Di-O-Methylate-(+)-Catechin) (5,7,4'-Tri-O-Methylate-(+)-Catechin) ((-)-Epicatechin 3-O-Β-D-Glucopyranoside) ((-)-Epicatechin 8-C-Β-D-Glucopyranoside) ((-)-Epicatechin 6-C-Β-D-Glucopyranoside) (-)-Epicatechin Cinnamtannin A2 Cinnamtannin A3 Procyanidin (Procyanidin B-2 6-C-Β-D-Glucopyranoside) Cinnzeylanine Cinncassiols Cinncassiols A Cinncassiols B Cinncassiols C3 Cinncassiols D1 Cinncassiols D3 Cinncassiols D4 Lyoniresinol-3Α-O-Β-D-Glucopyranoside 3,4,5-Trimethoxyphenol-Β-D-Apiofuranosyl(1→6)-Β-DGlucopyranoside Syringaresinol 5,7-Dimethyl-3',4'-Di-○-Methylene-(±)-Epicatechin Cinnamic Aldehydecyclicglycerol-1,3-Acetal(9,2'-Trans) Cinnamic Aldehydecyclicglycerol-1,3-Acetal(9,2'-Cis) Cassioside Cinnamoside D-Borneol Isoborneol
Table S3. SBP’s target proteins Compounds β-phenylpropionic acid β-phenylpropionic acid β-phenylpropionic acid β-phenylpropionic acid β-phenylpropionic acid β-phenylpropionic acid β-phenylpropionic acid β-elemane β-cadinene β-cadinene β-cadinene Vanillin,Vanillic acid,cis-cinnamic acid,cis-cinnamylcinnamate,3'-○-methyl -(-)-epicatechin,5,3'-di-O-methylate-(-)epicatechin,5,7,3'-tri-O-methylate-(-)-ep icatechin,〔4'-○-methyl-(+)-catechin〕, （7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin Vanillin,cis-cinnamic acid,cis-cinnamylcinnamate,3'-○-methyl -(-)-epicatechin,5,3'-di-O-methylate-(-)epicatechin,5,7,3'-tri-O-methylate-(-)-ep icatechin,〔4'-○-methyl-(+)-catechin〕, （7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin Vanillin Vanillin Ursodeoxycholic acid,Cholic acid,Glycocholic acid Ursodeoxycholic acid Ursodeoxycholic acid uracil uracil uracil uracil uracil uracil
Gene Symbol GOT1 GOT2 HADHA LPO MPO EPX GOT1L1 LTA4H TRIO KALRN ARHGEF25
Entrez 2805 2806 3030 4025 4353 8288 137362 4048 7204 8997 115557
Database STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
CA2
760
STITCH
CA1
759
STITCH
OR1G1 TRPV3
8390 162514
STITCH STITCH
FABP6
2172
HIT,STITCH
E2F1 NCOA1 CD69 CDA DPYD DPYS TYMP GPR17
1869 8648 969 978 1806 1807 1890 2840
HIT HIT STITCH STITCH STITCH STITCH STITCH STITCH
uracil uracil uracil uracil uracil uracil uracil uracil uracil uracil uracil uracil Testosterone,estradiol,Ginsenoside Fc,Ginsenoside Ra1,Ginsenoside Ra2,Ginsenoside Ra3,Ginsenoside Rb2(20-[(6-O-alpha-L-arabinopyranosyl -beta-D-glucopyranosyl)oxy]-12beta-hy droxydammar-24-en-3beta-yl 2-O-beta-D-glucopyranosyl-beta-D-gluc opyranoside),Ginsenoside Rb3(Dammarane,b-D-glucopyranoside deriv),Ginsenoside Rs1,Ginsenoside Rs2,Notoginsenoside Fa,Quinquenoside R1,(-)-epicatechin,cinnamtannin A2,cinnamtannin A3,（procyanidin B-2 6-C-β-D-glucopyranoside）,cinncassiols C3,cinnamoside Testosterone,estradiol,(-)-epicatechin Testosterone,estradiol,(-)-epicatechin Testosterone,estradiol Testosterone,estradiol Testosterone,estradiol Testosterone,estradiol Testosterone,Bufoserotonins A,Bufoserotonins B Testosterone,bilirubin,D-borneol Testosterone,bilirubin Testosterone Testosterone Testosterone Taurocholic acid,(-)-epicatechin Taurocholic acid Taurocholic acid
TDG TYMS UNG UPP1 CCNO SMUG1 UCKL1 AICDA PUS3 UPRT TRUB1 UPP2
6996 7298 7374 7378 10309 23583 54963 57379 83480 139596 142940 151531
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
AKT1
207
STITCH,HIT
CYP19A1 ABCG2 IGF1 IGFBP3 PRL SHBG
1588 9429 3479 3486 5617 6462
STITCH,HIT STITCH,HIT STITCH STITCH STITCH STITCH
POMC
5443
STITCH
UGT1A1 UGT1A6 HSD3B1 HSD17B3 HSD17B6 JUN GSR NR3C2
54658 54578 3283 3293 8630 3725 2936 4306
STITCH STITCH STITCH STITCH STITCH HIT,HIT HIT HIT
Taurocholic acid syringaresinol Sulfadiazine resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo talinin resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo talinin resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo talinin resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo talinin resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo talinin resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo talinin resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo
VEGFA NOS1 BRD2
7422 4842 6046
HIT STITCH STITCH
SERPINA6
866
STITCH
DRG1
4733
STITCH
PGK1
5230
STITCH
PHKA1
5255
STITCH
RPS12
6206
STITCH
TAF1
6872
STITCH
ECEL1
9427
STITCH
talinin resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo talinin resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo talinin resibufogenin,Resibufagin,gamabufotali n(Gamabufogenin),1β-Hydroxybufalin,b ufotalin,19-oxo-desacetyl-cinobufotalin, resibufogenol,cinobufaginol,Desacetyl-c inobufagin,Desacetylcinobufaginol,Bufo talinin protocatechuic acid,transcinnamic acid protocatechuic acid protocatechuic acid protocatechuic acid protocatechuic acid procyanidin procyanidin Pimaric Acid? Pimaric Acid? Pimaric Acid? Pimaric Acid? p-cymene（thymol） panaxadiol,panaxatrio1,oleanolic acid,3-epioleanolic acid,cinnzeylanine,cinncassiols A,cinncassiols B panaxadiol,panaxatrio1,Ginsenoside Rg3,bufalin,Vanillin palmitic acid palmitic acid palmitic acid palmitic acid palmitic acid oleanonic
GCN1L1
10985
STITCH
RWDD1
51389
STITCH
ZC3H15
55854
STITCH
MGA PRKACA PRKCA PRKCG PRKCZ CDK1 FOXO1 FCER1G KCNMA1 KCNMB1 SART1 ELANE
23269 5566 5578 5582 5590 983 2308 2207 3778 3779 9092 1991
HIT HIT HIT HIT HIT STITCH STITCH STITCH STITCH STITCH STITCH HIT
NR3C1
2908
HIT,STITCH
MMP9
4318
HIT,STITCH
IL10 PCYT1A PTEN SLC22A5 TEP1 GPBAR1
3586 5130 5728 6584 7011 151306
HIT HIT HIT HIT HIT STITCH
acid,Normuscone,3-methylcyclotridecan -2-one,cyclotetradecanone,oleanolic acid,Cholic acid,3-epioleanolic acid oleanolic acid,Ginsenoside Rf(Dammarane,b-D-glucopyranoside deriv),Ginsenoside Rg3,Ginsenoside Rh2,Deoxycholic acid,3-epioleanolic acid,linalool,cinnamaldehyde oleanolic acid,Ginsenoside Fc,Ginsenoside Ra1,Ginsenoside Ra2,Ginsenoside Ra3,Ginsenoside Rb2(20-[(6-O-alpha-L-arabinopyranosyl -beta-D-glucopyranosyl)oxy]-12beta-hy droxydammar-24-en-3beta-yl 2-O-beta-D-glucopyranosyl-beta-D-gluc opyranoside),Ginsenoside Rb3(Dammarane,b-D-glucopyranoside deriv),Ginsenoside Rs1,Ginsenoside Rs2,Notoginsenoside Fa,Quinquenoside R1,3-epioleanolic acid,cinnamaldehyde,cinnamoside oleanolic acid,5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid),3-epioleanolic acid oleanolic acid,3-epioleanolic acid,epoxycinnamyl cinnamate,cinnamtannin A2,cinnamtannin A3,（procyanidin B-2 6-C-β-D-glucopyranoside）,cassioside oleanolic acid,3-epioleanolic acid,dehydroabietic acid,linoleic acid oleanolic acid,3-epioleanolic acid oleanolic acid,3-epioleanolic acid oleanolic acid,3-epioleanolic acid oleanolic acid,3-epioleanolic acid oleanolic acid,3-epioleanolic acid oleanolic acid,3-epioleanolic acid Notoginsenoside R1 Normuscone,3-methylcyclotridecan-3-o ne,cyclotetradecanone,Testosterone Normuscone,3-methylcyclotridecan-1-o ne,cyclotetradecanone nicotinamide,cinncassiols C3
PTGS2
5743
STITCH,HIT,HIT
NFE2L2
4780
STITCH,HIT
TOP1
7150
STITCH
TOP2A
7153
STITCH
PPARA
5465
STITCH
CASP8 MAPK14 PTGIR PTGIS PTPN1 AKR1B10 SELE
841 1432 5739 5740 5770 57016 6401
STITCH STITCH STITCH STITCH STITCH STITCH HIT
AR
367
STITCH
HACL1
26061
STITCH
PARP1
142
STITCH
nicotinamide,adenine,uracil nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide nicotinamide myrcene myrcene myrcene myrcene myrcene myrcene myrcene myrcene myrcene myrcene myrcene Muscopyridine,Hydroxymuscopyridine A,Hydroxymuscopyridine B,beta-pinene Muscopyridine,Hydroxymuscopyridine A,Hydroxymuscopyridine B,beta-pinene Muscopyridine,Hydroxymuscopyridine A,Hydroxymuscopyridine B Muscopyran,Testosterone Muscopyran,Cholic acid,benzoic acid Muscol,estradiol,oleanolic acid,3-epioleanolic acid Muscol,Deoxycholic acid Muscol,Butanoic acid,4-terpineol Muscol Muscol
PNP PARP4 ART3 BST1 CD38 NNMT PARP3 NAMPT SIRT5 SIRT1 SIRT6 NMNAT1 TNKS2 PARP9 NAPRT1 ART5 PARP15 NMNAT3 ATP6V1E1 HOXA9 HOXD9 IPP RPS3A ZNF224 GGPS1 PDSS1 SAGE1 PDSS2 SDR16C5
4860 143 419 683 952 4837 10039 10135 23408 23411 51548 64802 80351 83666 93100 116969 165631 349565 529 3205 3235 3652 6189 7767 9453 23590 55511 57107 195814
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
CNGA2
1260
STITCH
CNGA3
1261
STITCH
OR8D1
283159
STITCH
CYP17A1 CES1
1586 1066
STITCH STITCH
CYP1A2
1544
STITCH
VCAM1 BCHE ACHE CD63
7412 590 43 967
STITCH,HIT STITCH STITCH STITCH
Muscol Muscol Muscol Muscol Methyl 4-hydroxycinnamate(methyl p-couma) marinobufagenin,Marinobufagin marinobufagenin,Marinobufagin marinobufagenin,Marinobufagin marinobufagenin,Marinobufagin marinobufagenin,Marinobufagin marinobufagenin,Marinobufagin marinobufagenin,Marinobufagin marinobufagenin,Marinobufagin marinobufagenin,Marinobufagin marinobufagenin,Marinobufagin lyoniresinol-3α-o-β-D-glucopyranoside linoleic acid linoleic acid linoleic acid linoleic acid linoleic acid linoleic acid linoleic acid linoleic acid linoleic acid linoleic acid linoleic acid linoleic acid linalool linalool limonene leucine L-cis-Diltiazem HCl l-benzoyl-3-phenylpropyne l，8-cineole l，8-cineole Isopimaric acid isoborneol isoborneol isoborneol isoborneol isoborneol
CFTR CYP2B6 CYP2C19 CYP2E1
1080 1555 1557 1571
STITCH STITCH STITCH STITCH
AKR1B1
231
STITCH
ATP4B CTSS DNAH8 ERG FGF10 FLI1 GNB3 REN SRC ATP11A MAP2K1 ALOX15 ALOX15B ACSL1 GPX2 FADS1 PLA2G1B FADS2 ELOVL2 ELOVL5 ACSBG2 PLA2G12B PLA2G4D ADORA2A KATNA1 BAD DROSHA CNGA1 NUCB1 IL5 PRODH PTGER2 SLC7A1 SLC7A2 SLC7A4 DICER1 SLC7A14
496 1520 1769 2078 2255 2313 2784 5972 6714 23250 5604 246 247 2180 2877 3992 5319 9415 54898 60481 81616 84647 283748 135 11104 572 29102 1259 4924 3567 5625 5732 6541 6542 6545 23405 57709
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH HIT HIT HIT STITCH STITCH STITCH HIT HIT STITCH STITCH STITCH STITCH STITCH STITCH
isoborneol Hyodeoxycholic acid,bilirubin Hyodeoxycholic acid Glycocholic acid,cinncassiols D4 Glycocholic acid Glycocholic acid Glycocholic acid Glycocholic acid Glycocholic acid Glycocholic acid Glycocholic acid Glycocholic acid Glycocholic acid Ginsenoside Ro Ginsenoside Rh2,cinnamaldehyde Ginsenoside Rh2 Ginsenoside Rh2 Ginsenoside Rh2 Ginsenoside Rh2 Ginsenoside Rh2 Ginsenoside Rh1,Ginsenoside Rh2 Ginsenoside Rh1,Ginsenoside Rh2 Ginsenoside Rg3,5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) Ginsenoside Rg3 Ginsenoside Rg3 Ginsenoside Rg2,Notoginsenoside R2 Ginsenoside Rg2,Notoginsenoside R2 Ginsenoside Rg2,Notoginsenoside R2 Ginsenoside Rg1,protocatechuic acid Ginsenoside Rg1,palmitic acid Ginsenoside Rg1,Butanoic acid,(-)-epicatechin Ginsenoside Rg1 ginsenoside rg1 Ginsenoside Rg1 Ginsenoside Rg1 Ginsenoside Rg1 Ginsenoside Rg1 Ginsenoside Rg1 Ginsenoside
SLC7A3 UGT2B4 GHDC CLPS BAAT CEL ODC1 PNLIP SCP2 SLCO1A2 ABCC3 SLCO1B1 SLCO1B3 AKTIP NFKBIA ADCYAP1 CASP1 MAP2K4 SLC2A4 PSMG1 BCL2A1 RHAG
84889 7363 84514 1208 570 1056 4953 5406 6342 6579 8714 10599 28234 64400 4792 116 834 6416 6517 8624 597 6005
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH HIT,HIT HIT HIT HIT HIT HIT STITCH STITCH
PPARG
5468
HIT,STITCH
HTR3A PRKAG2 GSK3B STK11 NR0B2 PRKCB COL1A1
3359 51422 2932 6794 8431 5579 1277
HIT HIT STITCH STITCH STITCH HIT,HIT HIT,HIT
IL2
3558
HIT,STITCH,HIT
ACTA2 ADRB2 CDH1 FN1 SMAD2 TGFB1 THBS1 IFNG
59 154 999 2335 4087 7040 7057 3458
HIT HIT HIT HIT HIT HIT HIT HIT,HIT
Rf(Dammarane,b-D-glucopyranoside deriv),Ginsenoside Rg3,Ginsenoside Rh2,limonene Ginsenoside Rf(Dammarane,b-D-glucopyranoside deriv),Ginsenoside Rg3,Ginsenoside Rh2,l，8-cineole,palmitic acid,(-)-epicatechin Ginsenoside Rf(Dammarane,b-D-glucopyranoside deriv),Ginsenoside Rg3,Ginsenoside Rh2,l，8-cineole Ginsenoside Rf(Dammarane,b-D-glucopyranoside deriv),Ginsenoside Rg1,Ginsenoside Rg3,limonene,l，8-cineole Ginsenoside Re,oleanolic acid,Ginsenoside Rd,Ginsenoside Rh2,bufalin,Butanoic acid,3-epioleanolic acid,(-)-epicatechin,cinncassiols C3 Ginsenoside Re,Ginsenoside Rg3,Ginsenoside Rh2,linalool Ginsenoside Re Ginsenoside Rd,Ginsenoside Re,Ursodeoxycholic acid,limonene,palmitic acid Ginsenoside Rd,Ginsenoside Re,Ginsenoside Rh2,bufalin,cinncassiols C3 Ginsenoside Rd Ginsenoside Rc,Ginsenoside Re Ginsenoside Rc Ginsenoside Rb1,Ginsenoside Rg1 ethylcinnamate estradiol,Ginsenoside Rg1,Bufoserotonins A,Bufoserotonins B,Benzyl cinnamate estradiol,Ginsenoside Rb1 estradiol,Bufoserotonins B,Abietatriene-3β-ol,4-ethyphenol estradiol,Abietatriene-3β-ol estradiol,?5-Hydroxymethyl-2-furaldehy de
TNF
7124
HIT,HIT
IL1B
3553
HIT,HIT
IL4
3565
HIT,HIT
CASP3
836
HIT,STITCH,HIT
NOS2
4843
HIT,HIT
NOS3
4846
HIT
BCL2
596
HIT,HIT
BAX
581
HIT,STITCH
PSMD3 FOS CYP2C9 AHR PDCL2
5709 2353 1559 196 132954
HIT HIT HIT HIT STITCH
CYP1A1
1543
STITCH,HIT
ESR2
2100
STITCH,HIT
ESR1
2099
STITCH
HSD17B1
3292
STITCH
SULT1A1
6817
STITCH
estradiol estradiol estradiol estradiol estradiol estradiol estradiol dihydrocoumarone dihydrocoumarone dihydrocoumarone desacetylbufotalin Deoxycholic acid,procyanidin,cinncassiols C3 Deoxycholic acid,limonene Deoxycholic acid Deoxycholic acid Deoxycholic acid Deoxycholic acid Deoxycholic acid Deoxycholic acid Deoxycholic acid Deoxycholic acid Deoxycholic acid Deoxycholic acid D-borneol D-borneol D-borneol D-borneol D-borneol D-borneol coumarin cinobufagin,Muscone,Muscol,Testoster one,oleanolic acid,Ginsenoside Rf(Dammarane,b-D-glucopyranoside deriv),bufalin,Ursodeoxycholic acid,Hyodeoxycholic acid,3-epioleanolic acid cinobufagin 3-acetate,1-hydroxy-cinobufagin,Cinobu fotalin,19-oxo-Cinobufotalin cinobufagin 3-acetate,1-hydroxy-cinobufagin,Cinobu fotalin,19-oxo-Cinobufotalin
GLUL OXTR ABCB1 SULT1E1 TFF1 NCOA3 HSD17B7 PON1 PON2 PON3 POLI
2752 5021 5243 6783 7031 8202 51478 5444 5445 5446 11201
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
TP53
7157
HIT,STITCH
HMGCR BIRC2 BAK1 EGFR GPT ICAM1 L1CAM MCL1 MUC2 PTPRG BAG3 OXT PPA1 RB1 ULK1 CAMKK2 CAMKK1 CYP2A13
3156 329 578 1956 2875 3383 3897 4170 4583 5793 9531 5020 5464 5925 8408 10645 84254 1553
HIT,HIT HIT HIT HIT HIT HIT HIT HIT HIT HIT HIT STITCH STITCH STITCH STITCH STITCH STITCH STITCH
CYP3A4
1576
STITCH,HIT
GLRA1
2741
STITCH
RRM2
6241
STITCH
cinnzeylanine,cinncassiols D1 cinnzeylanine,cinncassiols D1 cinnzeylanine,cinncassiols D1 cinnzeylanine,cinncassiols D1 cinnzeylanine,cinncassiols D1 cinnzeylanine,cinncassiols D1 cinnzeylanine,cinncassiols D1 cinnzeylanine,cinncassiols D1 cinnzeylanine,cinncassiols D1 cinnzeylanine,cinncassiols A,cinncassiols B cinncassiols,cinncassiols D3 cinncassiols,cinncassiols D3 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols D4 cinncassiols C3 Cinnamyl acetate,myrcene,cinnamyl acetate Cinnamyl acetate,myrcene,cinnamyl acetate Cinnamyl acetate,myrcene,cinnamyl acetate Cinnamyl acetate,cinnamyl acetate Cinnamyl acetate,cinnamyl acetate Cinnamyl acetate,cinnamyl acetate Cinnamyl acetate,cinnamyl acetate cinnamaldehyde cinnamaldehyde cinnamaldehyde cinnamaldehyde cinnamaldehyde
ACADL TBL1X CDK5RAP1 EXOSC4 IFT80 TBL1XR1 TBL1Y WDR17 EXOSC6
33 6907 51654 54512 57560 79718 90665 116966 118460
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
ADCY1
107
STITCH
MT1X DOCK4 AGA CHIT1 HEXA HEXB RAB27A SI RPL23 SF3B4 CHIA SIAE TASP1 ASRGL1 OVCA2 ASPG CCND1
4501 9732 175 1118 3073 3074 5873 6476 9349 10262 27159 54414 55617 80150 124641 374569 595
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
TKT
7086
STITCH
TKTL1
8277
STITCH
TKTL2
84076
STITCH
CPT1A CPT1B ARL5A CPT1C C5AR1 IFNB1 IRF3 RELA TLR4
1374 1375 26225 126129 728 3456 3661 5970 7099
STITCH STITCH STITCH STITCH HIT HIT HIT HIT HIT
cinnamaldehyde cinnamaldehyde cinnamaldehyde Cholic acid,Glycocholic acid Cholic acid,Glycocholic acid Cholic acid,Glycocholic acid Cholic acid,Glycocholic acid Cholic acid,Chenodeoxycholic acid,Glycocholic acid Cholic acid Cholic acid Cholic acid Cholic acid Cholic acid Cholic acid Cholic acid Cholic acid Cholesterol,Notoginsenoside R2 Cholesterol,Glycocholic acid Cholesterol,Deoxycholic acid Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol Cholesterol cholest-4-en-4-one,Testosterone cholest-4-en-3-one ,Cholesterol,Cholic acid,Deoxycholic acid cassioside cassioside cassioside cassioside cassioside cassioside
TXNRD1 TRPV1 TRPV4 SLC10A1 SLC10A2 ABCB11 SLC27A5
7296 7442 59341 6554 6555 8647 10998
HIT HIT HIT STITCH STITCH STITCH STITCH
NR1H4
9971
STITCH,HIT
COX5B COX6A2 COX6B1 COX7A1 COX7C ESRRG FECH COX5A SREBF2 ALB LDLR ABCA1 APOA1 APOB APOE CAV1 CETP CYP11A1 CYP27A1 LCAT LPA LPL SOAT1 SCAP ABCG8 AKR1D1
1329 1339 1340 1346 1350 2104 2235 9377 6721 213 3949 19 335 338 348 857 1071 1583 1593 3931 4018 4023 6646 22937 64241 6718
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH,HIT STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
CYP7A1
1581
STITCH,HIT
FDFT1 LSS RPE65 BCMO1 BCO2 ZNF644
2222 4047 6121 53630 83875 84146
STITCH STITCH STITCH STITCH STITCH STITCH
cassioside camphene calamenene Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Butanoic acid Bufoserotonins B,5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) Bufoserotonins A,Bufoserotonins B,5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) Bufoserotonins A,Bufoserotonins B Bufoserotonins A,Bufoserotonins B Bufoserotonins A,Bufoserotonins B Bufoserotonins A,Bufoserotonins B Bufoserotonins A,Bufoserotonins B Bufoserotonins A Bufoserotonins A bufalin,cinnamtannin A2,cinnamtannin A3,（procyanidin B-2 6-C-β-D-glucopyranoside） bufalin,cinnamtannin A2,cinnamtannin A3,（procyanidin B-2 6-C-β-D-glucopyranoside） bufalin,cinnamtannin A2,cinnamtannin A3,（procyanidin B-2 6-C-β-D-glucopyranoside）
ISPD CNR1 HTR1A CCK GAST GCG GCGR FFAR1 FFAR2 GSN NTS PTAFR TAC1 TACR2 TACR1 TACR3 TRH LPAR2 NPS
729920 1268 3350 885 2520 2641 2642 2864 2867 2934 4922 5724 6863 6865 6869 6870 7200 9170 594857
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
SPR
6697
STITCH
ASMT
438
STITCH
AANAT IDO1 MTNR1A MTNR1B NQO2 HTR1D HTR2A
15 3620 4543 4544 4835 3352 3356
STITCH STITCH STITCH STITCH STITCH STITCH STITCH
CASP9
842
STITCH
MAPK1
5594
STITCH
MAPK3
5595
STITCH
bufalin bufalin bufalin bufalin bufalin bufalin bilirubin,Vanillin,Vanillic acid,β-phenylpropionic acid bilirubin,Vanillin,Vanillic acid,β-phenylpropionic acid bilirubin,Vanillin,Vanillic acid,β-phenylpropionic acid bilirubin,D-borneol bilirubin,D-borneol bilirubin,D-borneol bilirubin,D-borneol bilirubin,coumarin bilirubin bilirubin bilirubin bilirubin bilirubin bilirubin bilirubin bilirubin bilirubin beta-pinene,myrcene beta-pinene,myrcene beta-pinene,myrcene beta-pinene beta-pinene Benzyl cinnamate Benzyl cinnamate Benzyl cinnamate Benzyl cinnamate Benzyl cinnamate Benzyl cinnamate Benzyl cinnamate benzoic acid benzoic acid benzoic acid benzoic acid benzoic acid
GNRH1 MAPK8 MAPK9 TF EIF2AK3 ZNF263
2796 5599 5601 7018 9451 10127
STITCH STITCH STITCH STITCH STITCH STITCH
UGT1A10
54575
STITCH
UGT1A8
54576
STITCH
UGT1A7
54577
STITCH
UGT1A5 UGT1A9 UGT1A4 UGT1A3 UGT2B15 ALPL ALPP ALPPL2 BLVRA HMOX1 HMOX2 UGT2B7 UGT2B10 UGT2B11 COLQ SPEN TPSD1 ALAS1 ST3GAL3 AKR1C2 NQO1 MT1A MT2A TXN MAFF FAM60A RAB9A HRSP12 GLYAT PRDX5 ACSM1
54579 54600 54657 54659 7366 249 250 251 644 3162 3163 7364 7365 10720 8292 23013 23430 211 6487 1646 1728 4489 4502 7295 23764 58516 9367 10247 10249 25824 116285
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
benzoic acid benzaldehyde benzaldehyde a-terpineol,(-)-epicatechin arenobufagin,Bufarenogin,Ψ-bufarenogi n （psi-bufarenogin),telocinobufagin,Buf otalidin(Hellebrigenin) alpha-pinene adenine,uracil adenine,cassioside adenine adenine adenine adenine adenine adenine adenine adenine adenine adenine adenine adenine adenine adenine adenine adenine adenine Abietatriene-3β-ol Abietatriene-3β-ol 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid),calamenene 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid
ACSM2B ALDH1A2 ALDH8A1 IL6
348158 8854 64577 3569
STITCH STITCH STITCH HIT
SDF4
51150
STITCH
LHFPL5 SLC29A2 SLC29A3 ACACB ACP1 ACVR2B ADA APRT HSP90AA1 MTAP PNMT PYGM SRPK2 STK24 SF3B1 SF3B14 CHFR PECR MRI1 ADAT3 STS RXRA
222662 3177 55315 32 52 93 100 353 3320 4507 5409 5837 6733 8428 23451 51639 55743 55825 84245 113179 412 6256
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
TH
7054
STITCH
ALDH2
217
STITCH
ALDH1B1
219
STITCH
ALDH9A1
223
STITCH
ALDH3A2
224
STITCH
(5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 4-ethyphenol 3-ethyphenol,β-phenylpropionic acid 3'-○-methyl-(-)-epicatechin,5,3'-di-O-me thylate-(-)-epicatechin,5,7,3'-tri-O-meth ylate-(-)-epicatechin, 〔4'-○-methyl-(+)-catechin〕, （7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin 3'-○-methyl-(-)-epicatechin,5,3'-di-O-me thylate-(-)-epicatechin,5,7,3'-tri-O-meth ylate-(-)-epicatechin, 〔4'-○-methyl-(+)-catechin〕, （7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin
AOX1
316
STITCH
CBR1
873
STITCH
DDC
1644
STITCH
GCH1
2643
STITCH
MAOA
4128
STITCH
MAOB
4129
STITCH
SLC6A4
6532
STITCH
TPH1
7166
STITCH
GPATCH1 TYR
55094 7299
STITCH STITCH
CA3
761
STITCH
CA4
762
STITCH
3'-○-methyl-(-)-epicatechin,5,3'-di-O-me thylate-(-)-epicatechin,5,7,3'-tri-O-meth ylate-(-)-epicatechin, 〔4'-○-methyl-(+)-catechin〕, （7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin 3'-○-methyl-(-)-epicatechin,5,3'-di-O-me thylate-(-)-epicatechin,5,7,3'-tri-O-meth ylate-(-)-epicatechin, 〔4'-○-methyl-(+)-catechin〕, （7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin 3'-○-methyl-(-)-epicatechin,5,3'-di-O-me thylate-(-)-epicatechin,5,7,3'-tri-O-meth ylate-(-)-epicatechin, 〔4'-○-methyl-(+)-catechin〕, （7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin 3'-○-methyl-(-)-epicatechin,5,3'-di-O-me thylate-(-)-epicatechin,5,7,3'-tri-O-meth ylate-(-)-epicatechin, 〔4'-○-methyl-(+)-catechin〕, （7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin 3'-○-methyl-(-)-epicatechin,5,3'-di-O-me thylate-(-)-epicatechin,5,7,3'-tri-O-meth ylate-(-)-epicatechin, 〔4'-○-methyl-(+)-catechin〕, （7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin 3'-○-methyl-(-)-epicatechin,5,3'-di-O-me thylate-(-)-epicatechin,5,7,3'-tri-O-meth ylate-(-)-epicatechin, 〔4'-○-methyl-(+)-catechin〕,
CA5A
763
STITCH
CA6
765
STITCH
CA7
766
STITCH
CA9
768
STITCH
CA12
771
STITCH
CA5B
11238
STITCH
（7,4'-di-O-methylate-(+)-catechin）, （5,7,4'-tri-O-methylate-(+)-catechin）, 5，7-dimethyl-3'， 4'-di-○-methylene-(±)-epicatechin 3，4， 5-trimethoxyphenol-β-D-apiofuranosyl( 1→6)-β-D-glucopyranoside 3，4， 5-trimethoxyphenol-β-D-apiofuranosyl( 1→6)-β-D-glucopyranoside 3，4， 5-trimethoxyphenol-β-D-apiofuranosyl( 1→6)-β-D-glucopyranoside 3，4， 5-trimethoxyphenol-β-D-apiofuranosyl( 1→6)-β-D-glucopyranoside 2-piperidinecarboxylic acid,benzoic acid 2-piperidinecarboxylic acid,5-Hydroxyindoleacetic acid (5-HIAA)(5-Hydroxyindole-3-acetic Acid) 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-piperidinecarboxylic acid 2-ethyphenol ?benzyl benzoate（Ascabin）,benzyl benzoate ?5-Hydroxymethyl-2-furaldehyde ?5-Hydroxymethyl-2-furaldehyde ?5-Hydroxymethyl-2-furaldehyde ?5-Hydroxymethyl-2-furaldehyde
AMY2A
279
STITCH
GANC
2595
STITCH
TGM4
7047
STITCH
GANAB
23193
STITCH
DAO
1610
STITCH
ALDH7A1
501
STITCH
ATP5A1 ATP5B ATP5C1 CAT F2 PEX1 PHYH PIN1 PREP CLPP GNPAT PREPL AASS PIPOX PEX26 FTL
498 506 509 847 2147 5189 5264 5300 5550 8192 8443 9581 10157 51268 55670 2512
STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH STITCH
LIPE
3991
STITCH
DCX HBA2 HBB SULT1A2
1641 3040 3043 6799
STITCH STITCH STITCH STITCH
（?(-)-epicatechin 3-O-β-D-glucopyranoside） （?(-)-epicatechin 3-O-β-D-glucopyranoside） （?(-)-epicatechin 3-O-β-D-glucopyranoside） （?(-)-epicatechin 3-O-β-D-glucopyranoside） （?(-)-epicatechin 3-O-β-D-glucopyranoside） （?(-)-epicatechin 3-O-β-D-glucopyranoside） (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin (-)-epicatechin （(-)-epicatechin 8-C-β-D-glucopyranoside ） （ (-)-epicatechin 6-C-β-D-glucopyranoside ）
RPL8
6132
STITCH
SLC5A1
6523
STITCH
TBP
6908
STITCH
TBPL1
9519
STITCH
MRPL2
51069
STITCH
TBPL2
387332
STITCH
COMT CREB1 ACE GCLC GRIA2 GRIN1 GSS HAS2 IL1A PLAT PLAU POR CCL2 DUOX2 CRTC2
1312 1385 1636 2729 2891 2902 2937 3037 3552 5327 5328 5447 6347 50506 200186
HIT HIT HIT HIT HIT HIT HIT HIT HIT HIT HIT HIT HIT HIT HIT
MANBA
4126
STITCH
SLC5A2
6524
STITCH
Table S4. SBP’s plasma absorbed compounds and their targets Component Muscone
Medicinal materials Moschus
Ginsenoside Rb1
Total ginsenoside ginseng root
Ginsenoside Rb2(20-[(6-O-alpha-L-arabinopyran
Total ginsenoside ginseng root
Target CYP3A4 AHR BHLHE76 ESR2 ESTRB NR3A2 NFE2L2 AKT1
Database STITCH
HIT
STITCH
osyl-beta-D-glucopyranosyl)oxy]-12 beta-hydroxydammar-24-en-3beta-yl 2-O-beta-D-glucopyranosyl-beta-Dglucopyranoside) Ginsenoside Rb3(Dammarane,b-D-glucopyranosi de deriv)
Total ginsenoside ginseng root
NFE2L2 AKT1
STITCH
CASP3
Ginsenoside Rd
Total ginsenoside ginseng root
Ginsenoside Rc
Total ginsenoside ginseng root
Ginsenoside Re
Total ginsenoside ginseng root
Ginsenoside Rg1
Total ginsenoside ginseng root
CPP32 PSMD3 BCL2 BCL2L4 BAX FOS G0S7 CYP2C9 CYP2C10 NOS3 BAX BCL2L4 NOS2 NOS2A CASP3 CPP32 BCL2 FOS G0S7 AHR BHLHE76 CYP1A1 ACTA2 ACTSA ACTVS GIG46 TGFB1 TGFB SMAD2 MADH2 MADR2 THBS1 TSP TSP1 CDH1
HIT
HIT
HIT
HIT
resibufogenin
Bufonis Venenum
gamabufotalin(Gamabufogenin)
Bufonis Venenum
arenobufagin
Bufonis Venenum
bufalin
Bufonis Venenum
CDHE UVO COL1A1 FN1 FN PRKCB PKCB PRKCB1 IL2 IL4 PHKA1 ECEL1 TAF1 ZC3H15 DRG1 SERPINA6 RPS12 PGK1 RWDD1 GCN1L1 PHKA1 ECEL1 TAF1 ZC3H15 DRG1 SERPINA6 RPS12 PGK1 RWDD1 GCN1L1 SDF4 CYP3A4 CASP3 BAX CASP9 EIF2AK3 GNRH1 TF ZNF263 MMP9 MAPK8 MAPK9 MAPK3
STITCH
STITCH
STITCH
STITCH
1β-Hydroxybufalin
Bufonis Venenum
bufotalin
Bufonis Venenum
telocinobufagin
Bufonis Venenum
Cinobufotalin
Bufonis Venenum
Ursodeoxycholic acid
Cholic acid
Bovis Calculus Artifactus
Bovis Calculus Artifactus
MAPK1 PHKA1 ECEL1 TAF1 ZC3H15 DRG1 SERPINA6 RPS12 PGK1 RWDD1 GCN1L1 PHKA1 ECEL1 TAF1 ZC3H15 DRG1 SERPINA6 RPS12 PGK1 RWDD1 GCN1L1 SDF4 RRM2 GLRA1 CYP3A4 CYP3A3 FABP6 ILBP ILLBP NCOA1 BHLHE74 SRC1 BCL2 E2F1 RBBP3 ABCB11 FABP6 CES1 FECH NR1H4 ESRRG MT-CO2 COX5A
STITCH
STITCH
STITCH STITCH HIT
HIT
HIT HIT HIT
STITCH
Deoxycholic acid
Bovis Calculus Artifactus
COX7A1 COX6A2 MT-CO3 MT-CO1 GPBAR1 COX5B COX6B1 CYP7A1 SLC10A2 COX7C SLC10A1 SLC27A5 BAG3 BIS BIRC2 API1 IAP2 MIHB RNF48 MCL1 BCL2L3 BAK1 BAK BCL2L7 CDN1 TP53 P53 MUC2 SMUC ICAM1 VCAM1 L1CAM PTGS2 COX2 PTPRG PTPG EGFR ERBB1 CYP7A1 CYP7 LDLR GPT AAT1
HIT
Chenodeoxycholic acid
Bovis Calculus Artifactus
Hyodeoxycholic acid
Bovis Calculus Artifactus
cinnamaldehyde
Styrax
cis-cinnamic acid
Styrax
benzyl benzoate
Styrax
D-borneol
Borneolum Syntheticum
GPT1 HMGCR NR1H4 BAR FXR HRR1 RIP14 UGT2B4 CYP3A4 GHDC C5AR1 C5AR C5R1 TRPV1 VR1 TRPV4 VRL2 VROAC NFKBIA IKBA MAD3 NFKBI NFE2L2 NRF2 TXNRD1 GRIM12 KDRF RELA NFKB3 IRF3 TLR4 PTGS2 COX2 IFNB1 IFB IFNB CA1 CA2 LIPE RB1 UGT1A5 UGT1A4 CAMKK2
HIT
STITCH
HIT
STITCH STITCH
STITCH
Borneolum Syntheticum
isoborneol
CAMKK1 UGT1A3 UGT1A9 PPA1 UGT1A1 ULK1 OXT SLC7A2 SLC7A4 SLC7A1 ENSG000001 88666 SLC7A3 SLC7A14 DICER1 RNASEN
STITCH
Table S5. Significant expressed genes and corresponding fold change values Gene_Symbol TRAF3IP3 GAD2 CYLC1 SYNGR1 NLGN4Y MME TACC1 TOX3 PRKDC LCN2 ZKSCAN8 C3orf18 LAMA4 HEXA-AS1 LOXL2 RBMXL2 TNIP3 ELTD1 KRT83 TNFSF14 EPS15L1 PRX
Entrez_Gene 80342 2572 1538 9145 22829 4311 6867 27324 5591 3934 7745 51161 3910 80072 4017 27288 79931 64123 3889 8740 58513 57716
foldchange 0.049808 18.57932 18.10809 0.061548 0.063076 15.64419 15.50599 15.42795 0.065013 14.43118 0.069429 0.06987 0.073016 0.074715 13.0397 13.02746 0.078097 12.73362 0.079213 0.079748 12.24958 0.082222
ZC2HC1C TEX13A MBL2 ANXA13 Igk PELO BAI3 CFI IGFBP7 CDH20 ECM2 SPAM1 EFCAB1 DIAPH3 SLC7A8 SAP30 PTPRT DPEP3 CDH15 ATXN3 MUSK XYLB LAMP3 BHMT MCM3AP ZNF135 MMP1 ISG20L2 OPRL1 DOCK5 CAMK1D ANGPTL2 TTLL7 PTK2B SEMA3D GABRA5 ELF5 EPM2A TLL1 ERV9-1 PPP1R3A PARVB TTC22
79696 56157 4153 312 243469 53918 577 3426 3490 28316 1842 6677 79645 81624 23428 8819 11122 64180 1013 4287 4593 9942 27074 635 8888 7694 4312 81875 4987 80005 57118 23452 79739 2185 223117 2558 2001 7957 7092 1.01E+08 5506 29780 55001
0.084623 11.79943 0.086092 11.44103 0.088902 0.088978 0.089595 0.093251 0.093929 0.094785 10.5127 0.095205 0.095469 10.46563 10.42589 10.38012 10.37189 10.33414 10.28328 0.097484 0.099133 0.10109 0.101299 9.857221 9.822597 0.10245 9.705378 9.703212 0.104977 0.105559 0.106208 0.106298 0.106309 0.107349 9.211773 0.109001 9.153281 0.109313 0.109628 9.060175 0.110831 0.110934 0.111884
RASL12 ELL2 FGF20 C14orf105 DSC2 CIB2 MIR1257///TAF4 PRKG1 ENTPD3 CASR TTTY2///TTTY2B ADAM22 PCCA TRPC6 UGT2B4 LZTS1 CD4 AQP4 CRHR1 FGB PDLIM4 NFATC4 GABRG2 MSR1 CCIN FAM65B CALD1 GCM2 SPOCK3 SOCS1 CDKN1C SIRPB1 IGH///IGHA1///IGHG1///IGHG2///IGHG3/// IGHM ADH1B ARPP21 CAMP RECK PLA2R1 SCG3
51285 22936 26281 55195 1824 10518 6874///100302 168 5592 956 846 60439///10010 1117 53616 5095 7225 7363 11178 920 361 1394 2244 8572 4776 2566 4481 881 9750 800 9247 50859 8651 1028 10326 3492///3493/// 3500///3501/// 3502///3507 125 10777 820 8434 22925 29106
0.112133 8.895335 0.112481 0.112763 8.817805 8.79141 8.785914 0.113837 8.776766 8.762664 8.760013 0.114552 0.115014 8.684741 8.669116 0.115721 0.116837 0.116923 0.11697 8.526688 0.11729 0.117306 0.117487 0.117944 8.473448 0.11856 0.118984 8.381394 0.119771 0.120055 8.310353 0.12066 8.282598 0.120986 0.122065 0.12253 8.156001 0.123234 0.123401
SPON1 HAL CCDC134 SELPLG LINC00965 PDPN DYRK3 CCDC102B IL5RA TIAM2 TEK PAK3 MST1L LOC101060620///MAPK8IP1 PDLIM5 HGF TNKS TAZ PCLO CD69 VSNL1 PTN CWH43 PSMB9 ABCB11 DCX TCF21 PTRF ECRP CDH6 CGA CALY C16orf70 ASTN1 SMARCA4 IGHD SMG7-AS1 DCHS2 CYP1B1 LOC100507388 LOC100996400///NOL4
10418 3034 79879 6404 349196 10630 8444 79839 3568 26230 7010 5063 11223 9479///101060 620 10611 3082 8658 6901 27445 969 7447 5764 80157 5698 8647 1641 6943 284119 643332 1004 1081 50632 80262 460 6597 3495 284649 54798 1545 1.01E+08 8715///100996 400
0.12396 0.124515 0.125059 7.97903 0.125383 0.127127 0.127329 0.127625 0.128061 7.80199 0.129225 0.129631 0.129675 7.70517 0.130006 7.691901 7.673146 0.130691 0.130696 7.629999 7.629885 7.629177 7.613785 0.131491 7.597977 7.581249 7.553765 0.132907 7.508783 7.48641 0.133665 7.472534 0.133868 7.46684 7.460428 7.406807 0.135044 0.13511 7.394989 0.135247 0.135313
EDA PTPN20A///PTPN20B MAGI2 CASP1 CCL23 SCGB1D1 CYP1A1 GPR98 DAB2 PTCD2 ADAM28 CCDC85B ALB MYF5 ENG IGF2BP3 PTGS2 CDKN2A HBA1///HBA2 DUSP1 PER2 CDKL5 IGHA1///IGHG1///IGHM///IGHV3-23///IGH V4-31 EMX2 MORN1 GIMAP1-GIMAP5///GIMAP5 GPLD1 PCSK5 APOB BAIAP3 ANKRD2 SLC23A2 RTDR1 MAP2K2 SLC16A4 AURKC BGN CMKLR1 LHCGR
1896 26095///65312 9 9863 834 6368 10648 1543 84059 1601 79810 10863 11007 213 4617 2022 10643 5743 1029 3039///3040 1843 8864 6792 3493///3500/// 3507///28396// /28442 2018 79906 55340///10052 7949 2822 5125 338 8938 26287 9962 27156 5605 9122 6795 633 1240 3973
0.13577 0.137094 0.137344 7.280741 7.246165 7.220643 7.197823 0.139598 0.139781 0.139878 0.139939 7.123477 0.140735 0.142132 0.142194 6.975194 0.144067 0.144933 0.144972 6.875058 6.858962 0.146056 0.146131 0.146491 0.146525 6.815763 6.783258 6.767327 0.148074 0.148099 6.744425 0.148304 0.148858 0.148968 6.709282 0.149083 0.149102 0.14968 0.149763
GRIP1 APOBEC3F///APOBEC3G GYPA CYP4F12 MAGEB4 EDNRA BIN1 KAT6A LINC00939 SLC4A7 LOC100130331 SV2B PPFIA2 NEFL TMEM257 CXCL14 SYNE1 NBLA00301 LOC441666 SOSTDC1 KRT33B FUT7 SRPX2 SEMA3G CCL5 GHSR SCN7A UTS2 SLCO2B1 PNPLA3 BRDT P2RX1 ABCA6 GNA15 PICK1 CFHR5 CD44 IGF1 KCNJ4 PARVB PLN CCR9
23426 60489///20031 6 2993 66002 4115 1909 274 7994 400084 9497 1E+08 9899 8499 4747 9142 9547 23345 79804 441666 25928 3884 2529 27286 56920 6352 2693 6332 10911 11309 80339 676 5023 23460 2769 9463 81494 960 3479 3761 29780 5350 10803
6.671348 0.150016 6.663177 6.642306 6.626046 6.608504 6.601771 6.595417 0.151836 6.584317 6.582577 0.151986 0.152439 6.548001 0.152855 0.153303 6.508186 0.153963 6.490143 6.488516 6.470345 6.454396 6.446732 0.156687 0.156795 0.157019 6.367043 0.157085 6.36024 6.345309 6.342818 0.157827 6.322789 0.158296 6.311152 6.305242 6.300612 0.158977 0.159144 6.283343 0.15949 6.262108
TCF4 ICAM2 TM6SF2 PTGES SLC39A9 MRC1 GFI1 SEC14L4 GFAP CACNG2 MAF ZNF132 CDK5R1 MLXIP CSAG2///CSAG3 HCP5 HSD17B2 C4BPB LRRN3 EPHB1 KIAA1045 GMFG CHM EFNA5 CHI3L1 FGF2 SMPX GPR17 MEG3 FGF2 RHCE KNG1 SPATA31C2 LALBA ACTL6B C9orf38 RAG1 CMKLR1 POPDC3 FKRP MTSS1 VCAN
6925 3384 53345 9536 55334 4360 2672 284904 2670 10369 4094 7691 8851 22877 389903///7284 61 10866 3294 725 54674 2047 23349 9535 1121 1946 1116 2247 23676 2840 55384 2247 6006 3827 645961 3906 51412 29044 5896 1240 64208 79147 9788 1462
0.159695 6.212491 0.162673 0.162882 6.133942 0.16316 0.164101 0.164126 0.164137 0.164205 0.164989 6.059267 0.165179 6.039835 5.990051 0.167732 5.949833 5.945282 0.168342 0.168436 0.168494 5.918256 0.169363 0.169618 0.16966 0.170339 5.85365 0.171199 5.825222 0.171904 0.172181 0.172281 0.172453 5.784084 0.173061 5.759905 5.756218 0.173813 0.173852 5.747948 5.745005 5.739205
6-Sep FABP7 ELK1 LGALS7///LGALS7B SNAP91 LOC100506403///RUNX1 LEF1 ESR1 CIITA GTPBP10 HPR FBXO17 GPX1 SCN3A DDC HLF B3GALT2 F13B PRDM10 VCAN PRPF31 FSHR CDA F2RL3 RECQL5 TAT MGC4294 PECAM1 TRIM31 NPL CES1///LOC100653057 IL7 CYP4F2 CEACAM21 TLL2 PRKAA2 SMOX FAM5B AVPR2 U2AF2 FAM5C
23157 2173 2002 3963///653499 9892 861///1005064 03 51176 2099 4261 85865 3250 115290 2876 6328 1644 3131 8707 2165 56980 1462 26121 2492 978 9002 9400 6898 79160 5175 11074 80896 1066///100653 057 3574 8529 90273 7093 5563 54498 57795 554 11338 339479
0.174491 0.174907 0.174992 5.706515 5.696224 5.69353 5.689237 5.678731 5.671998 0.176417 5.653687 5.649747 0.177258 0.177369 5.629318 0.177756 0.177996 0.178002 0.178138 0.178211 5.603477 5.597511 0.178766 5.582876 0.179167 5.571299 5.565525 0.179789 0.179794 0.179887 0.180399 0.180538 5.532467 5.530934 0.180842 0.181181 0.181637 0.181702 0.182131 0.182384 5.482328
B3GALT1 KIAA1661 PDCD1LG2 KCNB2 CEACAM1 KMT2A NEUROD2 COPE POLDIP3 BGN UGT1A1///UGT1A10///UGT1A3///UGT1A4 ///UGT1A5///UGT1A6///UGT1A7///UGT1A 8///UGT1A9 JAK3 PPFIA4 GPR3 ZAP70 CADM4 CACNA1I CXCL11 ACTL7B PTGER1 ADCYAP1 HDAC9 KIAA1967 AP4E1 CLUL1 CDKN1C PLCB2 RAB40A KCNG1 MLLT4 DAGLA LAPTM5 IGLC1 CLCN7 PCDHGA10///PCDHGA11///PCDHGA12/// PCDHGA3///PCDHGA5///PCDHGA6///PC DHGC3
8708 85375 80380 9312 634 4297 4761 11316 84271 633 54575///54576 ///54577///545 78///54579///5 4600///54657// /54658///5465 9 3718 8497 2827 7535 199731 8911 6373 10880 5731 116 9734 57805 23431 27098 1028 5330 142684 3755 4301 747 7805 3537 1186 5098///26025// /56105///5610 6///56109///56 110///56112
0.182514 0.182538 0.182757 0.182843 5.46452 5.464303 0.183135 0.18324 0.183289 5.452267
5.444446
0.184047 5.424242 5.391927 5.377475 5.371842 0.186231 5.368142 0.186855 5.345205 5.335639 5.333859 5.332472 5.318138 5.315793 5.312103 5.302396 5.299368 0.188731 5.294704 0.188877 5.291987 5.288474 5.285575 5.281698
PSG5 C14orf1 BCL11A TRPC3 ANGPT2 PLXNC1 BTN2A2 DNASE1 ATP2A3 STAB2 HOXA7 GRIP2 DNAJB5 CRYBA1 MC2R FAM182B///FAM27A///FAM27B///FAM27 C SPRR1A MYH4 MUC4 FOLH1 MPPE1 LAMA4 GRM8 NOTCH3 SLC6A6 NR2F6 BUB1 MFAP3L PSG2 TRIM15 CCL20 GPA33 C1orf186///LOC100505650 TNMD CBLN1 LOC101060181///ZNF44 KIR3DL2///LOC727787 ADAM3A SCGB1D2
5673 11161 53335 7222 285 10154 10385 1773 489 55576 3204 80852 25822 1411 4158 548321///7288 82///10013294 8///100133121 6698 4622 4585 2346 65258 3910 2918 4854 6533 2063 699 9848 5670 89870 6364 10223 440712///1005 05650 64102 869 51710///10106 0181 3812///727787 1587 10647
5.277557 5.253942 0.190902 0.191277 5.227882 0.191511 0.191971 5.195785 0.19254 0.192576 0.192689 5.174947 0.193616 5.153648 5.150732 0.194155 0.194298 5.137494 0.194662 5.133513 0.194899 0.195065 5.126296 5.126225 5.123775 0.195601 0.195997 0.196999 5.065988 5.064375 0.198221 5.039552 0.198569 0.198714 0.198716 5.031502 0.199451 5.011363 0.199663
SLC26A3 LTC4S VGLL1 LRRC32 N4BP2L1 IFNB1 LOC100506124///TTC21B FCER2 NCKIPSD TACR1 CRTAM IGHV5-78 CSN3 ZNF154 FLT1 PDPN FUT3 LOC100507472///PCSK6 CPM GPR132 PCDHGB6 XCL1 HIC2 MYCN PKD2L2 MOGAT2 GALR2 CEACAM3 ID2B SLC24A1 CDH6 HBE1 HCRP1 LIPE SLC15A1 GPR85 SLC7A8 TNIK KLK7 MASP1 WNT5B
1811 4056 51442 2615 90634 3456 79809///10050 6124 2208 51517 6869 56253 28387 1448 7710 2321 10630 2525 5046///100507 472 1368 29933 56100 6375 23119 4613 27039 80168 8811 1084 84099 9187 1004 3046 387535 3991 6564 54329 23428 23043 5650 5648 81029
5.007883 0.199985 0.200052 0.200356 0.200382 0.200548 0.200596 4.984489 0.200682 0.200781 0.20086 0.200963 4.949852 0.202151 0.202276 4.940035 4.931013 0.203107 4.922866 4.922575 4.913877 0.203546 4.90501 0.203975 4.901526 0.204024 4.897788 0.204564 0.205304 0.205461 0.20581 4.844616 4.842431 0.206557 0.206567 0.206874 0.207573 4.814631 0.207762 4.812777 0.208045
ERC2-IT1 KCNAB1 CDY1 AJAP1 C6orf15 MTNR1B ESRRG HOXA11 CDC42EP3 GATA4 KCNH1 DPT C20orf195 DPYSL4 DNMT3L MUC7 FOXO3///FOXO3B PDE4A TIE1 ZNF204P KIR2DL3 GULP1 BTN3A2 CEL F10 FEZF2 HS3ST1 KANSL3 CXCR2 WNT7B NRXN1 CACNA1H NFE2 HLA-DRA YME1L1 MAP4K2 MAGEA10-MAGEA5///MAGEA5 TSHZ2 IGH///IGHA2///IGHD///IGHG1 OR3A1 TRIM46
711 7881 9085 55966 29113 4544 2104 3207 10602 2626 3756 1805 79025 10570 29947 4589 2309///2310 5141 7075 7754 3804 51454 11118 1056 2159 55079 9957 55683 3579 7477 9378 8912 4778 3122 10730 5871 4104///100533 997 128553 3492///3494/// 3495///3500 4994 80128
0.208058 0.2081 0.208255 0.208435 0.208688 0.208781 4.777049 4.77543 4.774433 4.774418 4.765713 4.764085 0.210178 4.747357 0.210937 0.211101 4.736416 0.211139 4.73281 0.211383 0.211516 0.211794 0.211922 0.211981 4.717063 0.212006 4.712031 0.212244 0.212573 4.703215 4.698906 0.212866 0.212897 4.695531 0.21345 0.213893 0.214282 0.214409 0.21443 4.661118 4.656649
SLC7A8 GAGE1 CD1D GRIN1 SLC34A2 GNRHR ADD3-AS1 MS4A1 STAT2 TRIM3 ENTPD1 CELF2 KLHL35 INPP5D COL4A4 IPW///LOC100506948///SNORD107///SNO RD115-13///SNORD115-26///SNORD115-7/ //SNORD116-28///SNRPN MCHR1 PARVB PHYHIP INSL6 RFPL1 CCL13 NR0B2 CST1 IGFBP3 NRG2 PDYN CYP4F8 GPR12 ITGA8 VCX2 SUGP1 ATP8A1 KLK14 CLCA2 CXCR3 FBLN1 FOXE1
23428 2543 912 2902 10568 2798 1.01E+08 931 6773 10612 953 10659 283212 3635 1286 3653///6638/// 91380///10003 3444///100033 450///1000338 02///10003382 0///100506948 2847 29780 9796 11172 5988 6357 8431 1469 3486 9542 5173 11283 2835 8516 51480 57794 10396 43847 9635 2833 2192 2304
0.214914 0.215561 4.623247 0.216345 0.216387 4.61118 0.217093 4.600435 0.217624 4.59444 4.591823 4.587314 0.218049 4.582542 0.218448
4.575452
4.573281 4.570383 0.21885 4.56706 0.219027 0.219075 4.563859 0.220249 0.220257 4.53621 4.534907 4.531935 0.220786 0.220864 0.221083 0.221275 0.22131 0.221328 4.514545 4.512124 4.502183 4.492598
OPN1SW RPL35A DCHS1 GALR1 MNDA ICAM1 PPP1R3A LTF SAFB2 FGFR2 ACAA2 CHP2 KCNJ13 CCDC28B MDFIC CLCA1 SLC52A1 HMGCS2 LOC100129973 G6PC ZNF862 PNMA2 FCAR JAM2 CALD1 TRIM29 SNPH TCF7L2 DSCR4 TPSAB1 CDHR5 HFE GFRA2 LINC00652 GPM6B LZTS1 CD5L PDE4A CYTIP CLCN4 CD84 PON3 NEK9
611 6165 8642 2587 4332 3383 5506 4057 9667 2263 10449 63928 3769 79140 29969 1179 55065 3158 1E+08 2538 643641 10687 2204 58494 800 23650 9751 6934 10281 7177 53841 3077 2675 29075 2824 11178 922 5141 9595 1183 8832 5446 91754
4.487854 4.486049 0.223215 4.476715 0.223473 4.473712 0.22368 0.223887 4.466275 4.455691 0.22453 4.451845 4.448025 4.447669 4.438573 0.225814 0.226566 0.226632 4.406954 0.227037 0.22724 0.227415 0.227796 4.379757 4.376271 0.228748 4.360747 4.359842 4.354692 0.229838 0.230038 0.230202 4.34122 4.333482 4.324861 4.323023 0.231402 4.318118 0.231725 0.232038 0.23233 0.232415 0.23262
SNX29 IGHA1///IGHA2///IGHG1///IGHG4///IGHM ///IGHV4-31 CDC42EP4 APOL3 CDHR5 PAX3 GART TRIO MYH6 MS4A5 AHSG METTL10 LAMB4 DOC2B ADRBK1 CASR TAS2R8 OR2B6 OR12D3///OR5V1 ALDOB OSM ADAMTS8 SNN MAPK8IP3 EFCAB6 HMOX1 SLC6A6 ANXA10 KLF8 BANK1 KLRF1 HAO1 EIF2S2 PRMT2 HP///HPR LPAR1 HRH1 FBN1 PLIN1 CXCL2 LCMT2
92017 3493///3494/// 3500///3503/// 3507///28396 23580 80833 53841 5077 2618 7204 4624 64232 197 399818 22798 8447 156 846 50836 26212 81696///81797 229 5008 11095 8303 23162 64800 3162 6533 11199 11279 55024 51348 54363 8894 3275 3240///3250 1902 3269 2200 5346 2920 9836
0.232661 4.297695 0.232809 0.232852 4.29162 0.233321 4.282222 4.27639 4.272645 0.234066 4.268815 4.26673 0.234445 4.254913 0.235038 0.235447 0.235545 0.235546 0.235565 0.23574 0.235816 0.235901 0.235994 4.231425 0.236646 4.208924 4.208891 4.208301 0.237918 0.237967 0.238122 0.238156 0.238174 4.197706 0.238402 0.238816 0.238876 4.183925 0.239106 0.23943 0.239463
ADAM29 AFF3 SMARCA1 POU2F3 OR6A2 KMT2A ASIC1 KRT4 TGM2 PZP MYH13 CYLD C22orf43 TGFA SCN2B HGD C1S WISP1 ERGIC3 SLAMF7 BAALC HGD TONSL CELA3A COL13A1 SOX18 ZNF221 NID2 ALDH1A1 NCDN NRP2 RND1 CACNA1E CRYAB ALDH3B1 COL4A1 IGLJ3 TRMT1 IL2RA OSBPL10 IL5RA BPY2 TRAC///TRAJ17///TRAV20
11086 3899 6594 25833 8590 4297 41 3851 7052 5858 8735 1540 51233 7039 6327 3081 716 8840 51614 57823 79870 3081 4796 10136 1305 54345 7638 22795 216 23154 8828 27289 777 1410 221 1282 28831 55621 3559 114884 3568 9083 28663///28738
0.239472 4.172102 4.169445 0.239999 0.240191 4.162907 0.240353 4.158364 0.240736 4.153531 0.241222 0.241303 4.139056 0.241808 4.133081 4.127912 0.242311 4.126851 0.242881 4.112216 4.11185 0.243276 4.109574 0.243468 0.243818 0.244025 0.244298 0.244729 0.245012 4.073453 0.245619 0.245666 0.245667 4.070503 0.245739 0.246131 0.246152 0.246197 4.060918 0.246424 0.246707 4.053234 0.246803
///28755 10075 26108 10891 9567 2838 55086 27324 56926 6559 30849 4320 32 27178 6037 55753 4885 800
HUWE1 PYGO1 PPARGC1A GTPBP1 GPR15 CXorf57 TOX3 NCLN SLC12A3 PIK3R4 MMP11 ACACB IL37 RNASE3 OGDHL NPTX2 CALD1
4.048871 0.24699 0.247075 4.039788 4.032832 0.248201 4.016068 0.249145 4.010562 0.249425 0.249503 0.249538 4.006777 4.005261 0.249677 4.003965 4.001629
Table S6. Content of the 26 bioactive compounds in the SBPpc solution
NO.
Compound
Content (mg)
S-1
Muscone
1.05
S-2
Bufalin
4.95
S-3
Resibufogenin
3.33
S-4
Cinobufogenin/cinobufagin
0.64
S-5
Gamabufagin
0.63
S-6
Arenobufagin
0.62
S-7
Telocinobufagin
0.09
S-8
Bufotalin
0.23
S-9
Cinbufotalin
0.15
S-10
Cholic acid
5.1
S-11
Deoxycholic acid
0.88
S-12
Chenodeoxycholic acid
0.57
S-13
Hyodeoxycholic acid
0.44
S-14
Ursodeoxycholic acid
1.48
S-15
Cinnamic aldehyde
1.43
S-16
Cinnamic acid
0.36
S-17
Ginsenoside Rb1
7.65
S-18
Ginsenoside Rb2
4.64
S-19
Ginsenoside Rb3
2.43
S-20
Ginsenoside Rc
7.26
S-21
Ginsenoside Rd
4.73
S-22
Ginsenoside Re
7.27
S-23
Ginsenoside Rg1
8.75
S-24
Borneol
82.37
S-25
(+)-Borneol
31.63
S-26
Benzyl benzonate
8.37
Table S7. The 63 experimentally validated CVD pathways regulated by both SBPac and SBPpc Pathway ID
Pathway name
Pathway url
636
PID_LYMPHANGIOGENESIS_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_LYMPHANGIOGENESIS_PATHWAY
630
PID_S1P_S1P2_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_S1P_S1P2_PATHWAY
613
PID_SYNDECAN_2_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_SYNDECAN_2_PATHWAY
601
PID_VEGFR1_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_VEGFR1_PATHWAY
595
PID_AR_NONGENOMIC_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_AR_NONGENOMIC_PATHWAY
574
PID_ECADHERIN_KERATINOCYTE_PAT http://www.broadinstitute.org/gsea/msigdb/cards/PID_ECADHERIN_KERATINOCYTE_PATHWAY
HWAY
567
PID_ERBB2ERBB3PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_ERBB2ERBB3PATHWAY
548
PID_IL2_PI3KPATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_IL2_PI3KPATHWAY
536
PID_ERBB1_RECEPTOR_PROXIMAL_PAT http://www.broadinstitute.org/gsea/msigdb/cards/PID_ERBB1_RECEPTOR_PROXIMAL_PATHWAY
HWAY
533
PID_IL2_1PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_IL2_1PATHWAY
521
PID_S1P_S1P1_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_S1P_S1P1_PATHWAY
515
PID_ANGIOPOIETINRECEPTOR_PATHW http://www.broadinstitute.org/gsea/msigdb/cards/PID_ANGIOPOIETINRECEPTOR_PATHWAY
AY
493
PID_AVB3_OPN_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/PID_AVB3_OPN_PATHWAY
409
SA_B_CELL_RECEPTOR_COMPLEXES
http://www.broadinstitute.org/gsea/msigdb/cards/SA_B_CELL_RECEPTOR_COMPLEXES
TCGA_GLIOBLASTOMA_MUTATED
http://www.broadinstitute.org/gsea/msigdb/cards/TCGA_GLIOBLASTOMA_MUTATED
4030 4028
DING_LUNG_CANCER_MUTATED_RECU http://www.broadinstitute.org/gsea/msigdb/cards/DING_LUNG_CANCER_MUTATED_RECURRENTLY
RRENTLY
398
BIOCARTA_ARF_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_ARF_PATHWAY
397
BIOCARTA_TRKA_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_TRKA_PATHWAY
396
BIOCARTA_TFF_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_TFF_PATHWAY
394
BIOCARTA_CREB_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_CREB_PATHWAY
393
BIOCARTA_TPO_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_TPO_PATHWAY
381
BIOCARTA_TGFB_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_TGFB_PATHWAY
366
BIOCARTA_MET_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_MET_PATHWAY
353
BIOCARTA_ERK5_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_ERK5_PATHWAY
3521
BIERIE_INFLAMMATORY_RESPONSE_T http://www.broadinstitute.org/gsea/msigdb/cards/BIERIE_INFLAMMATORY_RESPONSE_TGFB1
GFB1
352
BIOCARTA_HER2_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_HER2_PATHWAY
351
BIOCARTA_CARDIACEGF_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_CARDIACEGF_PATHWAY
331
BIOCARTA_PTEN_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_PTEN_PATHWAY
321
BIOCARTA_CCR5_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_CCR5_PATHWAY
WU_HBX_TARGETS_3_DN
http://www.broadinstitute.org/gsea/msigdb/cards/WU_HBX_TARGETS_3_DN
311
BIOCARTA_NTHI_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_NTHI_PATHWAY
308
BIOCARTA_NGF_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_NGF_PATHWAY
299
BIOCARTA_EGFR_SMRTE_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_EGFR_SMRTE_PATHWAY
298
BIOCARTA_PYK2_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_PYK2_PATHWAY
292
BIOCARTA_INSULIN_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_INSULIN_PATHWAY
291
BIOCARTA_GLEEVEC_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_GLEEVEC_PATHWAY
290
BIOCARTA_RACCYCD_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_RACCYCD_PATHWAY
282
BIOCARTA_IL6_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_IL6_PATHWAY
280
BIOCARTA_IL4_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_IL4_PATHWAY
276
BIOCARTA_IGF1_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_IGF1_PATHWAY
275
BIOCARTA_HIF_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_HIF_PATHWAY
273
BIOCARTA_HCMV_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_HCMV_PATHWAY
250
BIOCARTA_EPO_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_EPO_PATHWAY
246
BIOCARTA_EGF_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_EGF_PATHWAY
2288
GALIE_TUMOR_ANGIOGENESIS
http://www.broadinstitute.org/gsea/msigdb/cards/GALIE_TUMOR_ANGIOGENESIS
214
BIOCARTA_CDMAC_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_CDMAC_PATHWAY
AGARWAL_AKT_PATHWAY_TARGETS
http://www.broadinstitute.org/gsea/msigdb/cards/AGARWAL_AKT_PATHWAY_TARGETS
3118
2083 207
BIOCARTA_BCELLSURVIVAL_PATHWA http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_BCELLSURVIVAL_PATHWAY
Y
204
BIOCARTA_SPPA_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_SPPA_PATHWAY
199
BIOCARTA_AT1R_PATHWAY
http://www.broadinstitute.org/gsea/msigdb/cards/BIOCARTA_AT1R_PATHWAY
DEBOSSCHER_NFKB_TARGETS_REPRES
http://www.broadinstitute.org/gsea/msigdb/cards/DEBOSSCHER_NFKB_TARGETS_REPRESSED_BY_GLU
SED_BY_GLUCOCORTICOIDS
COCORTICOIDS
SCHEIDEREIT_IKK_TARGETS
http://www.broadinstitute.org/gsea/msigdb/cards/SCHEIDEREIT_IKK_TARGETS
1956 1954 1942 1941
BAKER_HEMATOPOIESIS_STAT3_TARG http://www.broadinstitute.org/gsea/msigdb/cards/BAKER_HEMATOPOIESIS_STAT3_TARGETS
ETS BAKER_HEMATOPOESIS_STAT1_TARGE http://www.broadinstitute.org/gsea/msigdb/cards/BAKER_HEMATOPOESIS_STAT1_TARGETS
TS
1932
TURJANSKI_MAPK14_TARGETS
http://www.broadinstitute.org/gsea/msigdb/cards/TURJANSKI_MAPK14_TARGETS
1930
TURJANSKI_MAPK7_TARGETS
http://www.broadinstitute.org/gsea/msigdb/cards/TURJANSKI_MAPK7_TARGETS
1929 1928 1891
TURJANSKI_MAPK8_AND_MAPK9_TAR http://www.broadinstitute.org/gsea/msigdb/cards/TURJANSKI_MAPK8_AND_MAPK9_TARGETS
GETS TURJANSKI_MAPK1_AND_MAPK2_TAR http://www.broadinstitute.org/gsea/msigdb/cards/TURJANSKI_MAPK1_AND_MAPK2_TARGETS
GETS MARKS_HDAC_TARGETS_DN
http://www.broadinstitute.org/gsea/msigdb/cards/MARKS_HDAC_TARGETS_DN
1851
BUSA_SAM68_TARGETS_DN
http://www.broadinstitute.org/gsea/msigdb/cards/BUSA_SAM68_TARGETS_DN
172
KEGG_BLADDER_CANCER
http://www.broadinstitute.org/gsea/msigdb/cards/KEGG_BLADDER_CANCER
165
KEGG_PANCREATIC_CANCER
http://www.broadinstitute.org/gsea/msigdb/cards/KEGG_PANCREATIC_CANCER
REACTOME_ACTIVATION_OF_THE_AP1
1088
http://www.broadinstitute.org/gsea/msigdb/cards/REACTOME_ACTIVATION_OF_THE_AP1_FAMILY_OF
_FAMILY_OF_TRANSCRIPTION_FACTOR _TRANSCRIPTION_FACTORS
S
