Supplementary Material a Network Pharmacology Analysis to Explore the Effect of Astragali Radix-Radix Angelica Sinensis on Traumatic Brain Injury

Supplementary Material A network pharmacology analysis to explore the effect of Astragali Radix-Radix Angelica Sinensis on traumatic brain injury

Correspondence: Yang Wang: [email protected]; Zhihua Xing: [email protected]. Supplementary Table S1 Detailed information of all compounds in AR-RAS collected from the TCMSP database and literature, including 87 components of AR and 125 components of RAS. Herb Name MOL ID Molecule Name OB (%) DL Astragali Radix MOL000114 vanillic acid 35.47 0.04 Astragali Radix MOL000131 EIC 41.9 0.14 Astragali Radix MOL000211 Mairin 55.38 0.78 Astragali Radix MOL001955 Heriguard 11.93 0.33 Astragali Radix MOL000239 Jaranol 50.83 0.29 Astragali Radix MOL000251 Rhamnocitrin 12.9 0.27 Astragali Radix MOL000295 alexandrin 20.63 0.63 Astragali Radix MOL000296 hederagenin 36.91 0.75 (3S,8S,9S,10R,13R,14S,17R)-10,1 3-dimethyl-17-[(2R,5S)-5-propan-2 Astragali Radix MOL000033 -yloctan-2-yl]-2,3,4,7,8,9,11,12,14, 36.23 0.78 15,16,17-dodecahydro-1H-cyclope nta[a]phenanthren-3-ol Astragali Radix MOL000354 isorhamnetin 49.6 0.31 Astragali Radix MOL000356 lupeol 12.12 0.78 Astragali Radix MOL000371 3,9-di-O-methylnissolin 53.74 0.48 Astragali Radix MOL000372 3-Hydroxy-2-picoline 62.47 0.02 Astragali Radix MOL000373 (2S)-4-methoxy-7-methyl-2-[1-met 5.38 0.81 hyl-1-[(2S,3R,4S,5S,6R)-3,4,5-trih ydroxy-6-methylol-tetrahydropyran -2-yl]oxy-ethyl]-2,3-dihydrofuro[3, 2-g]chromen-5-one 5'-hydroxyiso-muronulatol-2',5'-di- Astragali Radix MOL000374 41.72 0.69 O-glucoside 5'-hydroxyiso-muronulatol-2',5'-di- Astragali Radix MOL000375 3.65 0.8 O-glucoside_qt 7,2'-dihydroxy-3',4'-dimethoxyisofl Astragali Radix MOL000376 16.16 0.86 avone-7-O-β-D-glucoside 7-hydroxy-3-(2-hydroxy-3,4-dimet Astragali Radix MOL000377 5.45 0.3 hoxy-phenyl)chromone Astragali Radix MOL000378 7-O-methylisomucronulatol 74.69 0.3 9,10-dimethoxypterocarpan-3-O-β- Astragali Radix MOL000379 36.74 0.92 D-glucoside (6aR,11aR)-9,10-dimethoxy-6a,11a Astragali Radix MOL000380 -dihydro-6H-benzofurano[3,2-c]chr 64.26 0.42 omen-3-ol 13-hydroxy-9,11-octadecadienoic Astragali Radix MOL000381 35.6 0.17 acid Astragali Radix MOL000382 Arabinose,d 1.87 0.02 Astragali Radix MOL000383 D-Galacturonic acid, homopolymer 29.75 0.04 Astragali Radix MOL000384 DL-Glucuronic acid 3.35 0.04 Astragali Radix MOL005928 isoferulic acid 50.83 0.06 Astragali Radix MOL000386 Fucopyranose, L- 42.51 0.03 Astragali Radix MOL000387 Bifendate 31.1 0.67 Astragali Radix MOL000388 gamma-aminobutyric acid 24.09 0.01 Astragali Radix MOL000389 FERULIC ACID (CIS) 54.97 0.06 Astragali Radix MOL000390 daidzein 19.44 0.19 Astragali Radix MOL000391 Ononin 11.52 0.78 Astragali Radix MOL000392 formononetin 69.67 0.21 Astragali Radix MOL000393 Soyasaponin I 2.06 0.05 Astragali Radix MOL000394 choline 0.47 0.01 Astragali Radix MOL000395 GGB 54.95 0.03 Astragali Radix MOL000396 (+)-Syringaresinol 3.29 0.72 Astragali Radix MOL000397 cis-p-Coumarate 45.98 0.04 Astragali Radix MOL000398 isoflavanone 109.99 0.3 Astragali Radix MOL000399 Docosanoate 15.69 0.26 Astragali Radix MOL000400 Flavaxin 18.18 0.5 Astragali Radix MOL000401 astragalosideI 46.79 0.11 Astragali Radix MOL000402 astragalosideI_qt 12.34 0.2 Astragali Radix MOL000403 astragalosideII 46.06 0.13 Astragali Radix MOL000404 astragalosideII_qt 11.55 0.25 Astragali Radix MOL000405 astragalosideⅢ 31.83 0.1 Astragali Radix MOL000406 astragalosideⅢ_qt 5.35 0.32 Astragali Radix MOL000407 astragalosideⅣ 22.5 0.15 Astragali Radix MOL000408 astragalosideⅣ_qt 7.07 0.32 Astragali Radix MOL000409 AstragalosideIV 17.74 0.15 Astragali Radix MOL000410 AstragalosideIV_qt 7.07 0.32 Astragali Radix MOL000411 Astraisoflavanin 18.37 0.86 Astragali Radix MOL000412 Mucronulatol 4.22 0.26 Astragali Radix MOL000413 astrachrysoside A 24.55 0.1 Astragali Radix MOL000414 Caffeate 54.97 0.05 Astragali Radix MOL000415 rutin 3.2 0.68 Astragali Radix MOL000416 Lariciresinol 5.53 0.38 Astragali Radix MOL000417 Calycosin 47.75 0.24 3'-Hydroxy-4'-methoxyisoflavone-7 Astragali Radix MOL000418 10.05 0.81 -O-beta-D-glucoside Astragali Radix MOL000419 astrasieversianin XV 11.19 0.07 Astragali Radix MOL000420 XLS 51.08 0.02 Astragali Radix MOL000421 nicotinic acid 47.65 0.02 Astragali Radix MOL000422 kaempferol 41.88 0.24 Astragali Radix MOL000423 rhamnocitrin-3-O-glucoside 2.87 0.76 Astragali Radix MOL000424 RAM 50.5 0.04 Astragali Radix MOL000425 asernestioside A 11.07 0.03 Astragali Radix MOL000426 asernestioside A_qt 24.55 0.1 Astragali Radix MOL000427 asernestioside B 12.54 0.03 Astragali Radix MOL000428 asernestioside B_qt 14.03 0.09 Astragali Radix MOL000429 Crystal VI 83.96 0.02 Astragali Radix MOL000430 betaine 40.92 0.01 Astragali Radix MOL000431 coumarin 29.17 0.04 Astragali Radix MOL000432 linolenic acid 45.01 0.15 Astragali Radix MOL000433 FA 68.96 0.71 Astragali Radix MOL000434 acetylastragaloside I 43.54 0.09 Astragali Radix MOL000435 acetylastragaloside I_qt 30.75 0.17 (Z)-1-(2,4-dihydroxyphenyl)-3-(4-h Astragali Radix MOL000436 87.51 0.15 ydroxyphenyl)prop-2-en-1-one Astragali Radix MOL000437 Hirsutrin 1.86 0.77 (3R)-3-(2-hydroxy-3,4-dimethoxyp Astragali Radix MOL000438 67.67 0.26 henyl)chroman-7-ol isomucronulatol-7,2'-di-O-glucosiol Astragali Radix MOL000439 49.28 0.62 e isomucronulatol-7,2'-di-O-glucosiol Astragali Radix MOL000440 23.42 0.79 e_qt Astragali Radix MOL000441 LUPENONE 11.66 0.78 1,7-Dihydroxy-3,9-dimethoxy Astragali Radix MOL000442 39.05 0.48 pterocarpene Astragali Radix MOL000054 L- 47.64 0.03 Astragali Radix MOL000061 Prolinum 77.57 0.01 Astragali Radix MOL000069 palmitic acid 19.3 0.1 Astragali Radix MOL000098 quercetin 46.43 0.28 Radix Angelica MOL000116 Nonanal 40.28 0.02 Sinensis Radix Angelica MOL000117 Cymol 27.2 0.02 Sinensis Radix Angelica MOL000121 Decanal 29.81 0.02 Sinensis Radix Angelica MOL001212 Loxanol V 14.19 0.05 Sinensis Radix Angelica MOL001224 Tridecylene 17.69 0.03 Sinensis Radix Angelica MOL000125 (-)-alpha-Pinene 46.25 0.05 Sinensis Radix Angelica MOL001273 80-57-9 50.63 0.06 Sinensis Radix Angelica MOL001302 Usaf hc-1 16.23 0.05 Sinensis Radix Angelica MOL001306 o-Acetyl-p-cresol 24.96 0.03 Sinensis Radix Angelica MOL001314 Azelex 16.9 0.04 Sinensis Radix Angelica MOL001388 (+)-Ledol 16.96 0.12 Sinensis Radix Angelica MOL001578 Hypnon 48.19 0.02 Sinensis Radix Angelica MOL000162 beta-Chamigrene 31.99 0.08 Sinensis Radix Angelica MOL001640 NON 26.74 0.03 Sinensis Radix Angelica MOL001788 adenine 62.81 0.03 Sinensis Radix Angelica MOL000197 Myrcene 24.96 0.02 Sinensis Radix Angelica MOL000199 Safrol 45.34 0.05 Sinensis Radix Angelica MOL000201 p-Ocimene 15.06 0.02 Sinensis Radix Angelica MOL000202 Moslene 33.02 0.02 Sinensis Radix Angelica MOL002029 ()-Cuparene 38.26 0.07 Sinensis Radix Angelica MOL002033 cis-Thujopsene 56.43 0.12 Sinensis Radix Angelica MOL000206 isoeugenol 70.1 0.04 Sinensis Radix Angelica MOL002098 3-Butylidene-7-hydroxyphthalide 62.68 0.08 Sinensis Radix Angelica MOL002102 Levistolid A 2.15 0.82 Sinensis Radix Angelica MOL002110 Allocymene 14.89 0.02 Sinensis Radix Angelica MOL002111 BdPh 42.44 0.07 Sinensis Radix Angelica MOL002143 senkyunolide-C 46.8 0.08 Sinensis Radix Angelica MOL002144 senkyunolide-D 79.13 0.1 Sinensis Radix Angelica MOL002145 senkyunolide-E 34.4 0.08 Sinensis Radix Angelica MOL002180 4-Octanone 19.37 0.01 Sinensis Radix Angelica MOL002184 (6R)-6-butylcyclohepta-1,4-diene 31.69 0.02 Sinensis Radix Angelica MOL002201 cis-ligustilide 51.3 0.07 Sinensis Radix Angelica MOL000023 Hemo-sol 39.84 0.02 Sinensis Radix Angelica MOL000232 ()-alpha-Terpineol 46.3 0.03 Sinensis Radix Angelica MOL002480 Methylbutenol 54.58 0.01 Sinensis Radix Angelica MOL000259 o-Thymol 43.28 0.03 Sinensis Radix Angelica MOL000270 CHEBI:7 45.2 0.04 Sinensis Radix Angelica MOL002830 PCR 51.99 0.01 Sinensis Radix Angelica (4S)-1-methyl-4-(6-methylhepta-1, MOL002972 20.3 0.06 Sinensis 5-dien-2-yl)cyclohexene Radix Angelica MOL002983 Guasol 51.6 0.02 Sinensis Radix Angelica MOL002998 IPH 36.05 0.01 Sinensis Radix Angelica MOL000346 succinic acid 29.62 0.01 Sinensis Radix Angelica MOL000035 beta-Selinene 24.39 0.08 Sinensis Radix Angelica MOL003534 CADINENE 17.12 0.08 Sinensis Radix Angelica MOL000357 Sitogluside 20.63 0.62 Sinensis Radix Angelica MOL000358 beta-sitosterol 36.91 0.75 Sinensis Radix Angelica MOL003587 Acoradiene 36.73 0.07 Sinensis Radix Angelica MOL000360 FER 39.56 0.06 Sinensis Radix Angelica MOL000383 D-Galacturonic acid, homopolymer 29.75 0.04 Sinensis Radix Angelica MOL000389 FERULIC ACID (CIS) 54.97 0.06 Sinensis Radix Angelica MOL000040 Scopoletol 27.77 0.08 Sinensis Radix Angelica MOL000421 nicotinic acid 47.65 0.02 Sinensis Radix Angelica MOL004474 Maruzen M 48.44 0.02 Sinensis Radix Angelica MOL004479 o-cresol 62.45 0.02 Sinensis Radix Angelica MOL004613 6,7,3',8'-diligustilide 9.83 0.7 Sinensis Radix Angelica MOL004723 beta-Terpinene 42.29 0.02 Sinensis Radix Angelica MOL004734 Butal 68.66 0 Sinensis Radix Angelica MOL000478 Eucarvone 53.14 0.03 Sinensis Radix Angelica MOL000479 Farnesene 17.42 0.05 Sinensis Radix Angelica MOL004791 Ethol 13.32 0.08 Sinensis Radix Angelica (1S,4aR,8aR)-1-isopropyl-7-methyl Sinensis MOL000489 -4-methylene-2,3,4a,5,6,8a-hexahy 19.8 0.08 dro-1H-naphthalene Radix Angelica MOL005125 ANN 29.69 0.03 Sinensis Radix Angelica MOL005449 h-Met-h 70.87 0.01 Sinensis Radix Angelica MOL000449 Stigmasterol 43.83 0.76 Sinensis Radix Angelica 3,4-DIMETHYLBENZALDEHYD MOL005589 39.99 0.02 Sinensis E Radix Angelica MOL005590 ETHYLBENZALDEHYDE 40.95 0.02 Sinensis Radix Angelica MOL005608 TMHYDROP 54.42 0.03 Sinensis Radix Angelica MOL000635 vanillin 52 0.03 Sinensis Radix Angelica MOL006440 bicycloelemene 20.89 0.08 Sinensis Radix Angelica MOL006869 WLN: QR CQ DV1 36.49 0.03 Sinensis Radix Angelica MOL000069 palmitic acid 19.3 0.1 Sinensis Radix Angelica MOL000705 WLN: VH6 19.59 0.01 Sinensis Radix Angelica MOL007745 WLN: QVR BVQ 17.74 0.04 Sinensis Radix Angelica (1R,2S,4R)-1-ethyl-1-methyl-2,4-bi MOL008244 15.01 0.06 Sinensis s(1-methylethyl)cyclohexane Radix Angelica MOL008245 DODECENE 17.74 0.02 Sinensis Radix Angelica MOL008246 phosphatdic acid 19.32 0.05 Sinensis Radix Angelica MOL008247 L-beta,gamma-Dimyristoyl-alpha-c 20.69 0.47 Sinensis ephalin Radix Angelica MOL008248 phosphatidylinositol 4.63 0.29 Sinensis Radix Angelica MOL008249 phosphatidylinositol_qt 12.66 0.05 Sinensis Radix Angelica MOL008250 ESEN 47.31 0.04 Sinensis Radix Angelica MOL008251 sedanolide 62.46 0.07 Sinensis Radix Angelica MOL008252 senkyunolide 68.28 0.07 Sinensis Radix Angelica MOL008253 sphingomyelin 0.31 0.51 Sinensis Radix Angelica MOL008254 Isotetandrine 10.42 0.1 Sinensis Radix Angelica MOL008255 α-acoradiene 40.98 0.07 Sinensis Radix Angelica InChI=1/C15H24/c1-10-7-8-15-9-1 Sinensis MOL008256 2(10)14(3,4)13(15)6-5-11(15)2/h7, 55.56 0.1 11-13H,5-6,8-9H2,1-4H Radix Angelica MOL008257 α-copaene 29.33 0.12 Sinensis Radix Angelica (1R,4R,5S)-4-isopropenyl-1,8-dime MOL008258 40.65 0.07 Sinensis thylspiro[4.5]dec-8-ene Radix Angelica MOL008259 2,6-di(phenyl)thiopyran-4-thione 69.13 0.15 Sinensis Radix Angelica MOL008260 o-Xylenol 53.13 0.02 Sinensis Radix Angelica MOL008261 2,4,6-trimethyl-Octane 29.14 0.02 Sinensis Radix Angelica MOL008262 Mesitaldehyde 37.8 0.03 Sinensis Radix Angelica MOL008263 Isoxylaldehyde 38.85 0.02 Sinensis Radix Angelica MOL008264 (E)-octadec-3-ene 19.5 0.09 Sinensis Radix Angelica MOL008265 2-valerylbenzoic acid 78.26 0.06 Sinensis Radix Angelica MOL008266 (Z)-2-Hexenyl hexanoate 19.39 0.04 Sinensis Radix Angelica MOL008267 2-Methylhexadecanoic acid 20.23 0.11 Sinensis Radix Angelica MOL008268 cis-Isoeugenol 20.73 0.04 Sinensis Radix Angelica MOL008269 2-methyl-5-decanone 20.4 0.11 Sinensis Radix Angelica MOL008270 2-methyldodecan-5-one 13.16 0.04 Sinensis Radix Angelica MOL008271 3,7-dimethyl-nonane 16.97 0.02 Sinensis Radix Angelica 1,1,5-trimethyl-2-formylcyclohexa- MOL008272 48.94 0.04 Sinensis 2,5-diene-4-one Radix Angelica MOL008273 4-Methyl-6-hepten-3-one 78.38 0.01 Sinensis Radix Angelica MOL008274 6-Ethylresorcinol 46.45 0.03 Sinensis Radix Angelica MOL008275 5-Indolol 63.14 0.03 Sinensis Radix Angelica MOL008276 Undecanol-6 25.77 0.02 Sinensis Radix Angelica 7,10-PENTADECADIYNOIC MOL008277 41.5 0.09 Sinensis ACID Radix Angelica 4-chloro-N-[1-methyl-5-[[1-methyl MOL008278 7.18 0.31 Sinensis -5-[[1-methyl-5-(2-morpholinoethyl carbamoyl)pyrrol-3-yl]carbamoyl]p yrrol-3-yl]carbamoyl]pyrrol-3-yl]-5 -[2-(2-pyridyl)ethylamino]isothiazo le-3-carboxamide Radix Angelica MOL008279 Amyl ketone 18.65 0.02 Sinensis Radix Angelica MOL008280 Isoamylbenzene 35.69 0.03 Sinensis Radix Angelica (Z)-2-[[(Z)-2-methylbut-2-enoyl]ox MOL008281 77.1 0.04 Sinensis ymethyl]but-2-enoic acid Radix Angelica MOL008282 Tropone 47.41 0.01 Sinensis Radix Angelica MOL008283 aromadendrene 18.21 0.1 Sinensis Radix Angelica MOL008284 BUA 21.62 0 Sinensis Radix Angelica (3S)-3-butyl-3H-isobenzofuran-1-o MOL008285 55.05 0.07 Sinensis ne Radix Angelica MOL008286 ()-Camphoric acid 99.13 0.07 Sinensis Radix Angelica (3E)-3-butylidene-7-hydroxy-2-ben MOL008287 42.17 0.08 Sinensis zofuran-1-one Radix Angelica MOL008288 Coniferyl ferulate 4.54 0.39 Sinensis Radix Angelica MOL008290 lecithin 0.31 0.4 Sinensis Radix Angelica MOL008291 2,4-Xylylaldehyde 39.33 0.03 Sinensis Radix Angelica MOL008292 m-Ethylphenol 51.3 0.02 Sinensis Radix Angelica MOL008293 1,5,5,6-tetramethyl-1,3-Cyclohexad 39.22 0.03 Sinensis iene Radix Angelica MOL000885 Dodekan 17.74 0.02 Sinensis Radix Angelica MOL000967 bergamotene 28.51 0.09 Sinensis Radix Angelica MOL000974 cuminal 38.29 0.03 Sinensis

Supplementary Table S2 19 compounds and 226 target proteins of AR-RAS. Ingredients Related Targets Gene names 7-O-Methylisomucronulatol Nitric oxide synthase, inducible NOS2 7-O-Methylisomucronulatol Prostaglandin G/H synthase 1 PTGS1 7-O-Methylisomucronulatol Dopamine D1 receptor DRD1 Muscarinic acetylcholine 7-O-Methylisomucronulatol CHRM3 receptor M3 7-O-Methylisomucronulatol Thrombin F2 Potassium voltage-gated channel 7-O-Methylisomucronulatol KCNH2 subfamily H member 2 Muscarinic acetylcholine 7-O-Methylisomucronulatol CHRM1 receptor M1 7-O-Methylisomucronulatol Estrogen receptor ESR1 7-O-Methylisomucronulatol Androgen receptor AR 7-O-Methylisomucronulatol Beta-1 adrenergic receptor ADRB1 Sodium channel protein type 5 7-O-Methylisomucronulatol SCN5A subunit alpha Peroxisome proliferator activated 7-O-Methylisomucronulatol PPARG receptor gamma 7-O-Methylisomucronulatol Coagulation factor Xa F10 Muscarinic acetylcholine 7-O-Methylisomucronulatol CHRM5 receptor M5 7-O-Methylisomucronulatol Prostaglandin G/H synthase 2 PTGS2 7-O-Methylisomucronulatol Nitric-oxide synthase, endothelial NOS3 7-O-Methylisomucronulatol Alpha-2C adrenergic receptor ADRA2C Muscarinic acetylcholine 7-O-Methylisomucronulatol CHRM4 receptor M4 Retinoic acid receptor 7-O-Methylisomucronulatol RXRA RXR-alpha 7-O-Methylisomucronulatol Delta-type opioid receptor OPRD1 CGMP-inhibited 3',5'-cyclic 7-O-Methylisomucronulatol PDE3A phosphodiesterase A 7-O-Methylisomucronulatol 5-hydroxytryptamine 2A receptor HTR2A 7-O-Methylisomucronulatol Alpha-1A adrenergic receptor ADRA1A Muscarinic acetylcholine 7-O-Methylisomucronulatol CHRM2 receptor M2 7-O-Methylisomucronulatol Alpha-1B adrenergic receptor ADRA1B Sodium-dependent dopamine 7-O-Methylisomucronulatol SLC6A3 transporter 7-O-Methylisomucronulatol Beta-2 adrenergic receptor ADRB2 7-O-Methylisomucronulatol Alpha-1D adrenergic receptor ADRA1D Sodium-dependent serotonin 7-O-Methylisomucronulatol SLC6A4 transporter 7-O-Methylisomucronulatol Estrogen receptor beta ESRRB Gamma-aminobutyric acid 7-O-Methylisomucronulatol GABRA1 receptor subunit alpha-1 7-O-Methylisomucronulatol Dipeptidyl peptidase IV DPP4 Mitogen-activated protein kinase 7-O-Methylisomucronulatol MAPK14 14 7-O-Methylisomucronulatol Glycogen synthase kinase-3 beta GSK3B 7-O-Methylisomucronulatol Heat shock protein HSP 90 HSP 90 7-O-Methylisomucronulatol Cell division protein kinase 2 CDK2 Serine/threonine-protein kinase 7-O-Methylisomucronulatol CHEK1 Chk1 mRNA of PKA Catalytic Subunit 7-O-Methylisomucronulatol PRKACA C-alpha 7-O-Methylisomucronulatol Retinoic acid receptor RXR-beta RXRB 7-O-Methylisomucronulatol Trypsin-1 PRSS1 Proto-oncogene 7-O-Methylisomucronulatol serine/threonine-protein kinase PIM1 Pim-1 7-O-Methylisomucronulatol Cyclin-A2 CCNA2 7-O-Methylisomucronulatol Nuclear receptor coactivator 2 NCOA2 Calcium-activated potassium 7-O-Methylisomucronulatol KCNMA1 channel subunit alpha 1 7-O-Methylisomucronulatol Calmodulin CALM Formononetin Nitric oxide synthase, inducible NOS2 Formononetin Prostaglandin G/H synthase 1 PTGS1 Muscarinic acetylcholine Formononetin CHRM1 receptor M1 Formononetin Estrogen receptor ESR2 Formononetin Androgen receptor AR Peroxisome proliferator activated Formononetin PPARG receptor gamma Formononetin Prostaglandin G/H synthase 2 PTGS2 Retinoic acid receptor Formononetin RXRA RXR-alpha CGMP-inhibited 3',5'-cyclic Formononetin PDE3A phosphodiesterase A Formononetin Alpha-1A adrenergic receptor ADRA1A Sodium-dependent dopamine Formononetin SLC6A3 transporter Formononetin Beta-2 adrenergic receptor ADRB2 Sodium-dependent serotonin Formononetin SLC6A4 transporter Formononetin Estrogen receptor beta MAOB Formononetin Dipeptidyl peptidase IV DPP4 Mitogen-activated protein kinase Formononetin MAPK14 14 Formononetin Glycogen synthase kinase-3 beta GSK3B Formononetin Heat shock protein HSP 90 HSP90 Formononetin Cell division protein kinase 2 CDK2 Amine oxidase Formononetin PKIA [flavin-containing] B Serine/threonine-protein kinase Formononetin CHEK1 Chk1 mRNA of PKA Catalytic Subunit Formononetin PRKACA C-alpha Formononetin Trypsin-1 PRSS1 Proto-oncogene Formononetin serine/threonine-protein kinase PIM1 Pim-1 Formononetin Cyclin-A2 CCNA2 Formononetin Calmodulin CALM cAMP-dependent protein kinase Formononetin ACHE inhibitor alpha Formononetin Thrombin F2 Formononetin Nitric-oxide synthase, endothelial NOS3 Formononetin Acetylcholinesterase LACTB2 Formononetin Beta-lactamase JUN Formononetin Transcription factor AP-1 IL4 Peroxisome proliferator-activated Formononetin PPARG receptor gamma Formononetin Interleukin-4 SIRT1 NAD-dependent deacetylase Formononetin ATP5F1B sirtuin-1 ATP synthase subunit beta, Formononetin MT-ND6 mitochondrial NADH-ubiquinone Formononetin HSD3B2 oxidoreductase chain 6 3 beta-hydroxysteroid Formononetin dehydrogenase/Delta HSD3B1 5-->4-isomerase type 2 3 beta-hydroxysteroid Formononetin dehydrogenase/Delta HTR3A 5-->4-isomerase type 1 FA Cell division protein kinase 2 CDK2 FA Thrombin F2 FA Glycogen synthase kinase-3 beta GSK3B (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Nitric oxide synthase, inducible NOS2 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Prostaglandin G/H synthase 1 PTGS1 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, Muscarinic acetylcholine 11a-dihydro-6H-benzofurano[3, CHRNA7 receptor M3 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Thrombin F2 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, Muscarinic acetylcholine 11a-dihydro-6H-benzofurano[3, CHRM1 receptor M1 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Estrogen receptor ESR1 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, Sodium channel protein type 5 11a-dihydro-6H-benzofurano[3, SCN5A subunit alpha 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Prostaglandin G/H synthase 2 PTGS2 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, 5-hydroxytryptamine receptor 3A NCOA1 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, Retinoic acid receptor 11a-dihydro-6H-benzofurano[3, PGR RXR-alpha 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Acetylcholinesterase LACTB2 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Alpha-1B adrenergic receptor ADRA1B 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, Beta-2 adrenergic receptor ADRB2 11a-dihydro-6H-benzofurano[3, 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Alpha-1D adrenergic receptor ADRA1D 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, Gamma-aminobutyric acid 11a-dihydro-6H-benzofurano[3, GABRA1 receptor subunit alpha-1 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Heat shock protein HSP 90 HSP 90 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, Neuronal acetylcholine receptor 11a-dihydro-6H-benzofurano[3, OPRM1 protein, alpha-7 chain 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Trypsin-1 PRSS1 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Nuclear receptor coactivator 2 NCOA2 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Nuclear receptor coactivator 1 NCOA1 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, 11a-dihydro-6H-benzofurano[3, Calmodulin CALM 2-c]chromen-3-ol (6aR,11aR)-9,10-dimethoxy-6a, Muscarinic acetylcholine 11a-dihydro-6H-benzofurano[3, CHRM4 receptor M4 2-c]chromen-3-ol Mairin Progesterone receptor PGR 3,9-Di-O-methylnissolin Nitric oxide synthase, inducible NOS2 3,9-Di-O-methylnissolin Prostaglandin G/H synthase 1 PTGS1 Muscarinic acetylcholine 3,9-Di-O-methylnissolin CHRNA7 receptor M3 3,9-Di-O-methylnissolin Thrombin F2 Muscarinic acetylcholine 3,9-Di-O-methylnissolin CHRM1 receptor M1 3,9-Di-O-methylnissolin Estrogen receptor ESR1 3,9-Di-O-methylnissolin Beta-1 adrenergic receptor ADRB1 Sodium channel protein type 5 3,9-Di-O-methylnissolin SCN5A subunit alpha 3,9-Di-O-methylnissolin Prostaglandin G/H synthase 2 PTGS2 3,9-Di-O-methylnissolin Nitric-oxide synthase, endothelial NOS3 3,9-Di-O-methylnissolin 5-hydroxytryptamine receptor 3A HTR3A 3,9-Di-O-methylnissolin Alpha-2C adrenergic receptor ADRA2C Retinoic acid receptor 3,9-Di-O-methylnissolin RXRA RXR-alpha 3,9-Di-O-methylnissolin Acetylcholinesterase LACTB2 CGMP-inhibited 3',5'-cyclic 3,9-Di-O-methylnissolin PDE3A phosphodiesterase A 3,9-Di-O-methylnissolin Alpha-1B adrenergic receptor ADRA1B 3,9-Di-O-methylnissolin Beta-2 adrenergic receptor ADRB2 3,9-Di-O-methylnissolin Alpha-1D adrenergic receptor ADRA1D 3,9-Di-O-methylnissolin Mu-type opioid receptor OPRM1 Gamma-aminobutyric acid 3,9-Di-O-methylnissolin GABRA1 receptor subunit alpha-1 3,9-Di-O-methylnissolin Trypsin-1 PRSS1 3,9-Di-O-methylnissolin Nuclear receptor coactivator 2 NCOA2 3,9-Di-O-methylnissolin Calmodulin CALM Jaranol Nitric oxide synthase, inducible NOS2 Jaranol Prostaglandin G/H synthase 1 PTGS1 Jaranol Androgen receptor AR Sodium channel protein type 5 Jaranol SCN5A subunit alpha Jaranol Prostaglandin G/H synthase 2 PTGS2 Jaranol Estrogen receptor beta MAOB Jaranol Dipeptidyl peptidase IV DPP4 Jaranol Heat shock protein HSP 90 HSP 90 Jaranol Cell division protein kinase 2 CDK2 Serine/threonine-protein kinase Jaranol CHEK1 Chk1 Jaranol Trypsin-1 PRSS1 Jaranol Nuclear receptor coactivator 2 NCOA2 Jaranol Calmodulin CALM Isorhamnetin Nitric oxide synthase, inducible NOS2 Isorhamnetin Prostaglandin G/H synthase 1 PTGS1 Isorhamnetin Estrogen receptor ESR1 Isorhamnetin Androgen receptor AR Peroxisome proliferator activated Isorhamnetin PPARG receptor gamma Isorhamnetin Prostaglandin G/H synthase 2 PTGS2 mRNA of Protein-tyrosine Isorhamnetin PTPN1 phosphatase, non-receptor type 1 Isorhamnetin Estrogen receptor beta MAOB Isorhamnetin Dipeptidyl peptidase IV DPP4 Mitogen-activated protein kinase Isorhamnetin MAPK14 14 Isorhamnetin Glycogen synthase kinase-3 beta GSK3B Isorhamnetin Heat shock protein HSP 90 HSP 90 Isorhamnetin Cell division protein kinase 2 CDK2 Phosphatidylinositol-4,5-bisphos Isorhamnetin phate 3-kinase catalytic subunit, PIK3CG gamma isoform mRNA of PKA Catalytic Subunit Isorhamnetin PRKACA C-alpha Isorhamnetin Trypsin-1 PRSS1 Proto-oncogene Isorhamnetin serine/threonine-protein kinase PIM1 Pim-1 Isorhamnetin Cyclin-A2 CCNA2 Isorhamnetin Nuclear receptor coactivator 2 NCOA2 Isorhamnetin Calmodulin CALM Glycogen phosphorylase, muscle Isorhamnetin PYGM form Peroxisome proliferator activated Isorhamnetin PPARD receptor delta Serine/threonine-protein kinase Isorhamnetin CHEK1 Chk1 Isorhamnetin Aldose reductase AKR1B1 Isorhamnetin Nuclear receptor coactivator 1 NCOA1 Isorhamnetin Coagulation factor VII F7 Isorhamnetin Thrombin F2 Isorhamnetin Nitric-oxide synthase, endothelial NOS3 Isorhamnetin Acetylcholinesterase LACTB2 Gamma-aminobutyric acid Isorhamnetin GABRA1 receptor subunit alpha-1 Isorhamnetin Amine oxidase PKIA [flavin-containing] B Isorhamnetin Glutamate receptor 2 GRIA2 Isorhamnetin Cytochrome P450-cam CAMC Isorhamnetin Transcription factor p65 RELA Isorhamnetin Xanthine dehydrogenase/oxidase XDH Isorhamnetin Neutrophil cytosol factor 1 NCOA1 Oxidized low-density lipoprotein Isorhamnetin OLR1 receptor 1 isomucronulatol-7,2'-di-O-gluc DNA topoisomerase II TOP2 osiole Calycosin Nitric oxide synthase, inducible NOS2 Calycosin Prostaglandin G/H synthase 1 PTGS1 Calycosin Estrogen receptor ESR1 Calycosin Androgen receptor AR Peroxisome proliferator activated Calycosin PPARG receptor gamma Calycosin Prostaglandin G/H synthase 2 PTGS2 Retinoic acid receptor Calycosin RXRA RXR-alpha CGMP-inhibited 3',5'-cyclic Calycosin PDE3A phosphodiesterase A Calycosin Estrogen receptor beta MAOB Calycosin Dipeptidyl peptidase IV DPP4 Mitogen-activated protein kinase Calycosin MAPK14 14 Calycosin Glycogen synthase kinase-3 beta GSK3B Calycosin Heat shock protein HSP 90 HSP 90 Calycosin Cell division protein kinase 2 CDK2 Calycosin Serine/threonine-protein kinase CHEK1 Chk1 mRNA of PKA Catalytic Subunit Calycosin PRKACA C-alpha Calycosin Trypsin-1 PRSS1 Proto-oncogene Calycosin serine/threonine-protein kinase PIM1 Pim-1 Calycosin Cyclin-A2 CCNA2 Calycosin Nuclear receptor coactivator 2 NCOA2 Calycosin Calmodulin CALM Calycosin Beta-2 adrenergic receptor ADRB2 quercetin Prostaglandin G/H synthase 1 PTGS1 quercetin Androgen receptor AR Peroxisome proliferator activated quercetin PPARG receptor gamma quercetin Prostaglandin G/H synthase 2 PTGS2 quercetin Heat shock protein HSP 90 HSP 90 Phosphatidylinositol-4,5-bisphos quercetin phate 3-kinase catalytic subunit, PIK3CG gamma isoform quercetin Nuclear receptor coactivator 2 NCOA2 quercetin Dipeptidyl peptidase IV DPP4 quercetin Aldose reductase AKR1B1 quercetin Trypsin-1 PRSS1 quercetin DNA topoisomerase II TOP2 quercetin Thrombin F2 Potassium voltage-gated channel quercetin KCNH2 subfamily H member 2 quercetin Sodium channel protein type 5 SCN5A subunit alpha quercetin Coagulation factor Xa F10 quercetin Beta-2 adrenergic receptor ADRB2 quercetin Stromelysin-1 MMP3 mRNA of PKA Catalytic Subunit quercetin PRKACA C-alpha quercetin Coagulation factor VII F7 quercetin Nitric-oxide synthase, endothelial NOS3 Retinoic acid receptor quercetin RXRA RXR-alpha quercetin Acetylcholinesterase LACTB2 Gamma-aminobutyric acid quercetin GABRA1 receptor subunit alpha-1 Amine oxidase quercetin PKIA [flavin-containing] B quercetin Transcription factor p65 RELA quercetin Epidermal growth factor receptor EGFR RAC-alpha quercetin AKT1 serine/threonine-protein kinase Vascular endothelial growth quercetin VEGFA factor A quercetin G1/S-specific cyclin-D1 CCND1 quercetin Apoptosis regulator Bcl-2 BCL2 quercetin Bcl-2-like protein 1 BCL2L1 quercetin Proto-oncogene c-Fos FOS Cyclin-dependent kinase quercetin CDKN1 inhibitor 1 Eukaryotic translation initiation quercetin EIF6 factor 6 quercetin Apoptosis regulator BAX BAX quercetin Caspase-9 CASP9 Urokinase-type plasminogen quercetin PLAU activator quercetin 72 kDa type IV collagenase MMP2 quercetin Matrix metalloproteinase-9 MMP9 Mitogen-activated protein kinase quercetin MAPK1 1 quercetin Interleukin-10 IL10 quercetin Pro-epidermal growth factor EGF Retinoblastoma-associated quercetin RB1 protein quercetin Tumor necrosis factor TNF quercetin Transcription factor AP-1 IL4 quercetin Interleukin-6 IL6 Cyclin-dependent kinase quercetin CDKN2A inhibitor 2A, isoforms 1/2/3 Activator of 90 kDa heat shock quercetin AHSA1 protein ATPase homolog 1 quercetin Caspase-3 CASP3 quercetin Cellular tumor antigen p53 TP53 ETS domain-containing protein quercetin ELK1 Elk-1 quercetin NF-kappa-B inhibitor alpha NFKBIA NADPH--cytochrome P450 quercetin POR reductase quercetin Ornithine decarboxylase ODC1 quercetin Xanthine dehydrogenase/oxidase XDH quercetin Caspase-8 CASP8 quercetin DNA topoisomerase 1 TOP1 RAF proto-oncogene quercetin RAF1 serine/threonine-protein kinase quercetin Superoxide dismutase [Cu-Zn] SOD1 quercetin Protein kinase C alpha type PRKCA quercetin Interstitial collagenase MMP1 quercetin Hypoxia-inducible factor 1-alpha HIF1A Signal transducer and activator of quercetin STAT1 transcription 1-alpha/beta quercetin Protein CBFA2T1 RUNX1T1 Probable E3 ubiquitin-protein quercetin HERC5 ligase HERC5 Cell division control protein 2 quercetin CDK1 homolog quercetin 78 kDa glucose-regulated protein HSPA5 Receptor tyrosine-protein kinase quercetin ERBB2 erbB-2 Peroxisome proliferator-activated quercetin PPARG receptor gamma quercetin Acetyl-CoA carboxylase 1 ACACA quercetin Heme oxygenase 1 HMOX1 quercetin Cytochrome P450 3A4 CYP3A4 quercetin Cytochrome P450 1A2 CYP1A2 quercetin Caveolin-1 CAV1 quercetin Myc proto-oncogene protein MYC quercetin Tissue factor F3 quercetin Gap junction alpha-1 protein GJA1 quercetin Cytochrome P450 1A1 CYP1A1 quercetin Intercellular adhesion molecule 1 ICAM1 quercetin Interleukin-1 beta IL1B quercetin C-C motif chemokine 2 CCL2 quercetin E-selectin SELE quercetin Vascular cell adhesion protein 1 VCAM1 Prostaglandin E2 receptor EP3 quercetin PTGER3 subtype quercetin Interleukin-8 CXCL8 quercetin Protein kinase C beta type PRKCB Baculoviral IAP quercetin BIRC5 repeat-containing protein 5 quercetin Dual oxidase 2 DUOX2 quercetin Nitric oxide synthase, endothelial NOS3 quercetin Heat shock protein beta-1 HSPB1 Transforming growth factor quercetin TGFB1 beta-1 quercetin Estrogen sulfotransferase SULT1E1 quercetin Maltase-glucoamylase, intestinal MGAM quercetin Interleukin-2 IL2 Nuclear receptor subfamily 1 quercetin NR2C2 group I member 2 quercetin Cytochrome P450 1B1 CYP1B1 quercetin G2/mitotic-specific cyclin-B1 CCNB1 Tissue-type plasminogen quercetin PLAT activator quercetin Thrombomodulin THBD quercetin Plasminogen activator inhibitor 1 SERPINE1 quercetin Collagen alpha-1(I) chain COL1A1 quercetin Interferon gamma IFNG quercetin Arachidonate 5-lipoxygenase ALOX5 Phosphatidylinositol-3,4,5-trisph osphate 3-phosphatase and quercetin PTEN dual-specificity protein phosphatase PTEN quercetin Interleukin-1 alpha IL1A quercetin Myeloperoxidase MPO quercetin DNA topoisomerase 2-alpha TOP2A quercetin Neutrophil cytosol factor 1 NCF1 ATP-binding cassette sub-family quercetin ABCG2 G member 2 quercetin Hyaluronan synthase 2 HAS2 quercetin Glutathione S-transferase P GSTP1 Nuclear factor erythroid 2-related quercetin NFE2L2 factor 2 NAD(P)H dehydrogenase quercetin NQO1 [quinone] 1 quercetin Poly [ADP-ribose] polymerase 1 PARP1 quercetin Aryl hydrocarbon receptor AHR 26S proteasome non-ATPase quercetin PSMD3 regulatory subunit 3 Solute carrier family 2, facilitated quercetin SLC2A4 glucose transporter member 4 quercetin Collagen alpha-1(III) chain COL3A1 quercetin DNA gyrase subunit B GYRB quercetin C-X-C motif chemokine 11 CXCL11 quercetin C-X-C motif chemokine 2 CXCL2 DDB1- and CUL4-associated quercetin DCAF5 factor 5 quercetin Nuclear receptor subfamily 1 NR1I3 group I member 3 Serine/threonine-protein kinase quercetin CHEK2 Chk2 quercetin Insulin receptor INSR quercetin Claudin-4 CLDN4 Peroxisome proliferator-activated quercetin PPARA receptor alpha Peroxisome proliferator-activated quercetin PPARD receptor delta quercetin Heat shock factor protein 1 HSF1 quercetin C-reactive protein CRP quercetin C-X-C motif chemokine 10 CXCL10 Inhibitor of nuclear factor quercetin CHUK kappa-B kinase subunit alpha quercetin Osteopontin SPP1 Runt-related transcription factor quercetin RUNX2 2 Ras association quercetin RASSF1 domain-containing protein 1 quercetin Transcription factor E2F1 E2F1 quercetin Transcription factor E2F2 E2F2 quercetin Prostatic acid phosphatase ACPP quercetin Cathepsin D CTSD Insulin-like growth quercetin IGFBP3 factor-binding protein 3 quercetin Insulin-like growth factor II IGF2 quercetin CD40 ligand CD40LG quercetin Interferon regulatory factor 1 IRF1 quercetin Receptor tyrosine-protein kinase ERBB3 erbB-3 Serum paraoxonase/arylesterase quercetin PON1 1 quercetin Type I iodothyronine deiodinase DIO1 Procollagen C-endopeptidase quercetin PCOLCE enhancer 1 Puromycin-sensitive quercetin NPEPPS aminopeptidase quercetin Hexokinase-2 HK2 quercetin Homeobox protein Nkx-3.1 NKX3-1 quercetin Ras GTPase-activating protein 1 RASA1 quercetin Peroxidase C1A PRXC1A quercetin Glutathione S-transferase Mu 1 GSTM1 quercetin Glutathione S-transferase Mu 2 GSTM2 kaempferol Nitric oxide synthase, inducible NOS2 kaempferol Prostaglandin G/H synthase 1 PTGS1 kaempferol Androgen receptor AR Peroxisome proliferator activated kaempferol PPARG receptor gamma kaempferol Prostaglandin G/H synthase 2 PTGS2 kaempferol Heat shock protein HSP 90 HSP 90 Phosphatidylinositol-4,5-bisphos kaempferol phate 3-kinase catalytic subunit, PIK3CG gamma isoform mRNA of PKA Catalytic Subunit kaempferol PRKACA C-alpha kaempferol Nuclear receptor coactivator 2 NCOA2 kaempferol Dipeptidyl peptidase IV DPP4 kaempferol Trypsin-1 PRSS1 kaempferol Progesterone receptor PGR kaempferol Thrombin F2 Muscarinic acetylcholine kaempferol CHRM1 receptor M1 kaempferol Nitric-oxide synthase, endothelial NOS3 Gamma-aminobutyric-acid kaempferol GABRA2 receptor alpha-2 subunit kaempferol Acetylcholinesterase LACTB2 Sodium-dependent noradrenaline kaempferol SLC6A2 transporter Muscarinic acetylcholine kaempferol CHRM2 receptor M2 kaempferol Alpha-1B adrenergic receptor ADRA1B Gamma-aminobutyric acid kaempferol GABRA1 receptor subunit alpha-1 kaempferol DNA topoisomerase II TOP2 kaempferol Coagulation factor VII F7 kaempferol Calmodulin CALM kaempferol Transcription factor p65 RELA Inhibitor of nuclear factor kaempferol IKBKB kappa-B kinase subunit beta RAC-alpha kaempferol AKT1 serine/threonine-protein kinase kaempferol Apoptosis regulator Bcl-2 BCL2 kaempferol Apoptosis regulator BAX BAX kaempferol Tumor necrosis factor TNF kaempferol Transcription factor AP-1 IL4 Activator of 90 kDa heat shock kaempferol AHSA1 protein ATPase homolog 1 kaempferol Caspase-3 CASP3 Mitogen-activated protein kinase kaempferol MAPK8 8 kaempferol Xanthine dehydrogenase/oxidase XDH kaempferol Interstitial collagenase MMP1 Signal transducer and activator of kaempferol STAT1 transcription 1-alpha/beta Cell division control protein 2 kaempferol CDK1 homolog Peroxisome proliferator-activated kaempferol PPARG receptor gamma kaempferol Heme oxygenase 1 HMOX1 kaempferol Cytochrome P450 3A4 CYP3A4 kaempferol Cytochrome P450 1A2 CYP1A2 kaempferol Cytochrome P450 1A1 CYP1A1 kaempferol Intercellular adhesion molecule 1 ICAM1 kaempferol E-selectin SELE kaempferol Vascular cell adhesion protein 1 VCAM1 Nuclear receptor subfamily 1 kaempferol NR2C2 group I member 2 kaempferol Cytochrome P450 1B1 CYP1B1 kaempferol Arachidonate 5-lipoxygenase ALOX5 kaempferol Hyaluronan synthase 2 HAS2 1,7-Dihydroxy-3,9-dimethoxy Prostaglandin G/H synthase 2 PTGS2 pterocarpene 1,7-Dihydroxy-3,9-dimethoxy Retinoic acid receptor RXRA pterocarpene RXR-alpha 1,7-Dihydroxy-3,9-dimethoxy Heat shock protein HSP 90 HSP 90 pterocarpene 1,7-Dihydroxy-3,9-dimethoxy Trypsin-1 PRSS1 pterocarpene hederagenin Progesterone receptor PGR hederagenin Nuclear receptor coactivator 2 NCOA2 Muscarinic acetylcholine hederagenin CHRNA7 receptor M3 Muscarinic acetylcholine hederagenin CHRM1 receptor M1 Gamma-aminobutyric-acid hederagenin GABRA2 receptor alpha-2 subunit Gamma-aminobutyric-acid hederagenin GABRA3 receptor alpha-3 subunit Muscarinic acetylcholine hederagenin CHRM2 receptor M2 hederagenin Alpha-1B adrenergic receptor ADRA1B Gamma-aminobutyric acid hederagenin GABRA1 receptor subunit alpha-1 hederagenin Glutamate receptor 2 GRIA2 Gamma-aminobutyric-acid hederagenin GABRA6 receptor subunit alpha-6 Gamma-aminobutyric-acid hederagenin GABRA5 receptor alpha-5 subunit hederagenin Ig gamma-1 chain C region IGHG1 hederagenin Alcohol dehydrogenase 1B ALDH1B1 hederagenin Alcohol dehydrogenase 1C ALDH3A1 hederagenin Lysozyme LYZ1 Nicotinate-nucleotide--dimethylb hederagenin enzimidazole COBT phosphoribosyltransferase hederagenin Prostaglandin G/H synthase 1 PTGS1 Sodium channel protein type 5 hederagenin SCN5A subunit alpha hederagenin Prostaglandin G/H synthase 2 PTGS2 Retinoic acid receptor hederagenin RXRA RXR-alpha CGMP-inhibited 3',5'-cyclic hederagenin PDE3A phosphodiesterase A Sodium-dependent noradrenaline hederagenin SLC6A2 transporter hederagenin Cytochrome P450-cam CYP21A2 9,10-dimethoxypterocarpan-3- Prostaglandin G/H synthase 2 PTGS2 O-β-D-glucoside 9,10-dimethoxypterocarpan-3- DNA topoisomerase II TOP2 O-β-D-glucoside 9,10-dimethoxypterocarpan-3- Nuclear receptor coactivator 2 NCOA2 O-β-D-glucoside (3S,8S,9S,10R,13R,14S,17R)-10 ,13-dimethyl-17-[(2R,5S)-5-pro pan-2-yloctan-2-yl]-2,3,4,7,8,9, Progesterone receptor PGR 11,12,14,15,16,17-dodecahydro -1H-cyclopenta[a]phenanthren- 3-ol Bifendate Prostaglandin G/H synthase 2 PTGS2 Vascular endothelial growth Bifendate KDR factor receptor 2 Hepatocyte growth factor Bifendate MET receptor Bifendate Heat shock protein HSP 90 HSP 90 Calcium-activated potassium Bifendate KCNMA1 channel subunit alpha 1 Bifendate Prostaglandin G/H synthase 1 PTGS1 Bifendate DNA topoisomerase II TOP2 beta-sitosterol Progesterone receptor PGR beta-sitosterol Nuclear receptor coactivator 2 NCOA2 beta-sitosterol Prostaglandin G/H synthase 1 PTGS1 beta-sitosterol Prostaglandin G/H synthase 2 PTGS2 beta-sitosterol Heat shock protein HSP 90 HSP 90 Phosphatidylinositol-4,5-bisphos beta-sitosterol phate 3-kinase catalytic subunit, PIK3CG gamma isoform Potassium voltage-gated channel beta-sitosterol KCNH2 subfamily H member 2 mRNA of PKA Catalytic Subunit beta-sitosterol PRKACA C-alpha beta-sitosterol Dopamine D1 receptor DRD1 Muscarinic acetylcholine beta-sitosterol CHRNA7 receptor M3 Muscarinic acetylcholine beta-sitosterol CHRM1 receptor M1 Sodium channel protein type 5 beta-sitosterol SCN5A subunit alpha Gamma-aminobutyric-acid beta-sitosterol GABRA2 receptor alpha-2 subunit Muscarinic acetylcholine beta-sitosterol CHRM4 receptor M4 CGMP-inhibited 3',5'-cyclic beta-sitosterol PDE3A phosphodiesterase A beta-sitosterol 5-hydroxytryptamine 2A receptor HTR2A Gamma-aminobutyric-acid beta-sitosterol GABRA5 receptor alpha-5 subunit beta-sitosterol Alpha-1A adrenergic receptor ADRA1A Gamma-aminobutyric-acid beta-sitosterol GABRA3 receptor alpha-3 subunit Muscarinic acetylcholine beta-sitosterol CHRM2 receptor M2 beta-sitosterol Alpha-1B adrenergic receptor ADRA1B beta-sitosterol Beta-2 adrenergic receptor ADRB2 Neuronal acetylcholine receptor beta-sitosterol CHRNA2 subunit alpha-2 Sodium-dependent serotonin beta-sitosterol SLC6A4 transporter beta-sitosterol Mu-type opioid receptor OPRM1 Gamma-aminobutyric acid beta-sitosterol GABRA1 receptor subunit alpha-1 Neuronal acetylcholine receptor beta-sitosterol OPRM1 protein, alpha-7 chain beta-sitosterol Cytochrome P450-cam CYP21A2 beta-sitosterol Apoptosis regulator Bcl-2 BCL2 beta-sitosterol Apoptosis regulator BAX BAX beta-sitosterol Caspase-9 CASP9 beta-sitosterol Transcription factor AP-1 IL4 beta-sitosterol Caspase-3 CASP3 beta-sitosterol Caspase-8 CASP8 beta-sitosterol Protein kinase C alpha type PRKCA Transforming growth factor beta-sitosterol TGFB1 beta-1 Serum paraoxonase/arylesterase beta-sitosterol PON1 1 beta-sitosterol Microtubule-associated protein 2 MAP2 Stigmasterol Progesterone receptor PGR Stigmasterol Mineralocorticoid receptor NR3C2 Stigmasterol Nuclear receptor coactivator 2 NCOA2 Stigmasterol Alcohol dehydrogenase 1C ADH1C Stigmasterol Ig gamma-1 chain C region IGHG1 Retinoic acid receptor Stigmasterol RXRA RXR-alpha Stigmasterol Nuclear receptor coactivator 1 NCOA1 Stigmasterol Prostaglandin G/H synthase 1 PTGS1 Stigmasterol Prostaglandin G/H synthase 2 PTGS2 Stigmasterol Alpha-2A adrenergic receptor ADRA2A Sodium-dependent noradrenaline Stigmasterol SLC6A2 transporter Sodium-dependent dopamine Stigmasterol SLC6A3 transporter Stigmasterol Beta-2 adrenergic receptor ADRB2 Stigmasterol Aldose reductase AKR1B1 Urokinase-type plasminogen Stigmasterol PLAU activator Stigmasterol Leukotriene A-4 hydrolase LTA4H Amine oxidase Stigmasterol PKIA [flavin-containing] B Amine oxidase Stigmasterol MAOA [flavin-containing] A mRNA of PKA Catalytic Subunit Stigmasterol PRKACA C-alpha Stigmasterol Chymotrypsinogen B CTRB1 Muscarinic acetylcholine Stigmasterol CHRNA7 receptor M3 Muscarinic acetylcholine Stigmasterol CHRM1 receptor M1 Stigmasterol Beta-1 adrenergic receptor ADRB1 Sodium channel protein type 5 Stigmasterol SCN5A subunit alpha Stigmasterol 5-hydroxytryptamine 2A receptor HTR2A Stigmasterol Alpha-1A adrenergic receptor ADRA1A Gamma-aminobutyric-acid Stigmasterol GABRA3 receptor alpha-3 subunit Muscarinic acetylcholine Stigmasterol CHRM2 receptor M2 Stigmasterol Alpha-1B adrenergic receptor ADRA1B Gamma-aminobutyric acid Stigmasterol GABRA1 receptor subunit alpha-1 Neuronal acetylcholine receptor Stigmasterol OPRM1 protein, alpha-7 chain

Supplementary Table S3 Proteins targeted by 17 active compounds of AR-RAS were enrichened in 95 signal pathways(P<0.001).

Term FoldGene Count % P-Value Gene Benjami % P-Value Enrichmen Count ni t hsa05200:Pathways in 27.31958 1.30E-2 5.2947894 53 2.83E-22 cancer 763 4 98 17.52577 3.97E-2 9.2061128 hsa05161:Hepatitis B 34 4.31E-21 32 3 53 hsa05212:Pancreatic 11.34020 1.97E-1 13.288461 22 1.43E-16 cancer 619 8 54 hsa05223:Non-small cell 9.793814 6.70E-1 13.320819 19 3.62E-14 lung cancer 433 6 81 8.762886 8.26E-1 hsa05219:Bladder cancer 17 16.279102 3.38E-14 598 6 11.34020 2.03E-1 9.8153409 hsa05215:Prostate cancer 22 7.23E-14 619 5 09 hsa04668:TNF signaling 11.85567 9.86E-1 8.5189751 23 3.06E-13 pathway 01 5 29 hsa05222:Small cell lung 10.82474 1.34E-1 9.6998663 21 3.64E-13 cancer 227 4 1 hsa05142:Chagas disease 11.34020 7.46E-1 8.3052884 22 1.80E-12 (American trypanosomiasis) 619 4 62 11.34020 1.03E-1 7.3199152 hsa05145:Toxoplasmosis 22 2.23E-11 619 2 54 9.278350 1.05E-1 9.9535851 hsa05140:Leishmaniasis 18 2.07E-11 515 2 47 8.762886 1.43E-1 10.765212 hsa05210:Colorectal cancer 17 2.59E-11 598 2 61 hsa04620:Toll-like receptor 10.30927 1.16E-1 7.4078044 20 1.94E-10 signaling pathway 835 1 6 hsa05220:Chronic myeloid 8.762886 1.73E-1 9.2700441 17 2.68E-10 leukemia 598 1 92 hsa05205:Proteoglycans in 13.40206 2.28E-1 5.1039772 26 3.29E-10 cancer 186 1 73 hsa04066:HIF-1 signaling 9.793814 2.71E-1 7.6118970 19 3.68E-10 pathway 433 1 32 hsa05164:Influenza A 24 12.37113 4.88E-1 5.4153605 6.23E-10 402 1 02 10.82474 9.18E-1 6.1991626 hsa05160:Hepatitis C 21 1.11E-09 227 1 79 14.43298 1.81E-1 4.2942116 hsa05166:HTLV-I infection 28 2.07E-09 969 0 48 hsa05213:Endometrial 7.216494 3.03E-1 10.570367 14 3.29E-09 cancer 845 0 13 hsa04919:Thyroid hormone 9.793814 3.72E-1 6.5435606 19 3.84E-09 signaling pathway 433 0 06 hsa04151:PI3K-Akt 16.49484 4.16E-1 3.6416337 32 4.10E-09 signaling pathway 536 0 29 7.731958 5.26E-1 9.0603146 hsa05214:Glioma 15 4.96E-09 763 0 85 hsa04660:T cell receptor 9.278350 5.77E-1 6.8612091 18 5.22E-09 signaling pathway 515 0 79 hsa04068:FoxO signaling 10.30927 7.87E-1 5.8599050 20 6.83E-09 pathway 835 0 2 hsa04115:p53 signaling 7.731958 8.07E-1 8.7898575 15 6.73E-09 pathway 763 0 31 hsa05169:Epstein-Barr 11.85567 1.77E-0 4.7526913 23 1.42E-08 virus infection 01 9 88 7.216494 3.18E-0 8.8654692 hsa04210:Apoptosis 14 2.47E-08 845 9 08 hsa04380:Osteoclast 9.793814 3.79E-0 5.6943962 19 2.84E-08 differentiation 433 9 53 7.731958 3.87E-0 7.8522727 hsa05133:Pertussis 15 2.80E-08 763 9 27 10.82474 1.57E-0 4.6581278 hsa05152:Tuberculosis 21 1.10E-07 227 8 89 hsa04917:Prolactin 7.216494 1.83E-0 7.7416773 14 1.24E-07 signaling pathway 845 8 37 7.216494 1.83E-0 7.7416773 hsa05218:Melanoma 14 1.24E-07 845 8 37 hsa04020:Calcium 10.82474 1.91E-0 4.6060817 21 1.25E-07 signaling pathway 227 8 67 hsa04010:MAPK signaling 12.88659 2.02E-0 3.8491532 25 1.29E-07 pathway 794 8 98 hsa04080:Neuroactive 13.40206 2.32E-0 3.6851821 26 1.44E-07 ligand-receptor interaction 186 8 46 6.185567 2.54E-0 9.6150278 hsa05144:Malaria 12 1.53E-07 01 8 29 hsa04370:VEGF signaling 6.701030 2.83E-0 8.3671758 13 1.66E-07 pathway 928 8 57 hsa04012:ErbB signaling 7.731958 2.87E-0 6.7692006 15 1.64E-07 pathway 763 8 27 hsa04932:Non-alcoholic 9.793814 3.73E-0 4.9401715 19 2.08E-07 fatty liver disease (NAFLD) 433 8 83 hsa04071:Sphingolipid 8.762886 4.52E-0 5.5620265 17 2.45E-07 signaling pathway 598 8 15 8.247422 5.41E-0 5.9262435 hsa05146:Amoebiasis 16 2.86E-07 68 8 68 8.247422 6.99E-0 5.8164983 hsa04931:Insulin resistance 16 3.61E-07 68 8 16 hsa05143:African 5.154639 7.98E-0 11.897382 10 4.03E-07 trypanosomiasis 175 8 92 hsa04621:NOD-like 6.185567 9.13E-0 8.5661157 12 4.50E-07 receptor signaling pathway 01 8 02 hsa05221:Acute myeloid 12 6.185567 1.11E-0 8.4131493 5.36E-07 leukemia 01 7 51 10.82474 2.03E-0 4.0023720 hsa04510:Focal adhesion 21 9.58E-07 227 7 21 hsa04064:NF-kappa B 7.216494 2.26E-0 6.3179205 14 1.04E-06 signaling pathway 845 7 85 hsa05230:Central carbon 6.185567 4.66E-0 7.3615056 12 2.10E-06 metabolism in cancer 01 7 82 hsa05321:Inflammatory 6.185567 4.66E-0 7.3615056 12 2.10E-06 bowel disease (IBD) 01 7 82 hsa04725:Cholinergic 7.731958 6.56E-0 5.3055896 15 2.91E-06 synapse 763 7 81 hsa05206:MicroRNAs in 12.37113 6.77E-0 3.3062200 24 2.94E-06 cancer 402 7 96 5.670103 7.66E-0 7.9976851 hsa05134:Legionellosis 11 3.26E-06 093 7 85 hsa04014:Ras signaling 10.82474 9.10E-0 3.6481798 21 3.80E-06 pathway 227 7 07 hsa05132:Salmonella 6.701030 9.68E-0 6.1493702 13 3.96E-06 infection 928 7 08 8.247422 1.12E-0 4.7231715 hsa05162:Measles 16 4.48E-06 68 6 65 4.639175 1.17E-0 10.707644 hsa05020:Prion diseases 9 4.60E-06 258 6 63 hsa05323:Rheumatoid 6.701030 1.84E-0 5.7999741 13 7.12E-06 arthritis 928 6 74 hsa04024:cAMP signaling 9.793814 2.25E-0 3.7675045 19 8.57E-06 pathway 433 6 91 7.731958 2.55E-0 4.7493585 hsa04110:Cell cycle 15 9.54E-06 763 6 04 hsa05014:Amyotrophic 5.154639 3.58E-0 7.8522727 10 1.32E-05 lateral sclerosis (ALS) 175 6 27 hsa05202:Transcriptional 8.762886 4.65E-0 3.9728760 17 1.68E-05 misregulation in cancer 598 6 82 hsa05120:Epithelial cell 5.670103 5.97E-0 6.4458955 signaling in Helicobacter 11 2.12E-05 093 6 22 pylori infection hsa04915:Estrogen 6.701030 6.49E-0 5.1555325 13 2.27E-05 signaling pathway 928 6 99 hsa04662:B cell receptor 5.670103 7.84E-0 6.2590579 11 2.70E-05 signaling pathway 093 6 71 hsa04723:Retrograde 6.701030 8.01E-0 5.0534428 13 2.72E-05 endocannabinoid signaling 928 6 44 hsa04920:Adipocytokine 5.670103 8.94E-0 6.1696428 11 2.99E-05 signaling pathway 093 6 57 hsa04722:Neurotrophin 7.216494 9.34E-0 4.5804924 14 3.07E-05 signaling pathway 845 6 24 hsa04914:Progesterone-me 6.185567 1.06E-0 5.4153605 12 3.43E-05 diated oocyte maturation 01 5 02 6.185567 1.18E-0 5.3538223 hsa04540:Gap junction 12 3.77E-05 01 5 14 hsa05168:Herpes simplex 8.762886 1.40E-0 3.6472305 17 4.39E-05 infection 598 5 02 hsa04726:Serotonergic 6.701030 2.13E-0 4.5981777 13 6.59E-05 synapse 928 5 23 hsa05031:Amphetamine 5.154639 3.73E-0 5.9486914 10 1.14E-04 addiction 175 5 6 hsa04910:Insulin signaling 7.216494 4.23E-0 3.9830368 14 1.27E-04 pathway 845 5 91 hsa05231:Choline 6.185567 4.42E-0 4.6647164 12 1.31E-04 metabolism in cancer 01 5 72 hsa04664:Fc epsilon RI 5.154639 4.75E-0 5.7737299 10 1.39E-04 signaling pathway 175 5 47 hsa05203:Viral 8.762886 5.69E-0 3.2558203 17 1.65E-04 carcinogenesis 598 5 99 hsa04622:RIG-I-like 5.154639 6.01E-0 5.6087662 10 1.72E-04 receptor signaling pathway 175 5 34 hsa04060:Cytokine-cytokine 9.278350 6.59E-0 3.0726284 18 1.86E-04 receptor interaction 515 5 58 hsa04062:Chemokine 8.247422 6.76E-0 3.3773216 16 1.88E-04 signaling pathway 68 5 03 3.608247 7.09E-0 9.4768808 hsa05216:Thyroid cancer 7 1.95E-04 423 5 78 hsa04923:Regulation of 4.639175 7.26E-0 6.3098620 9 1.97E-04 lipolysis in adipocytes 258 5 13 hsa04022:cGMP-PKG 7.731958 7.30E-0 3.5477135 15 1.96E-04 signaling pathway 763 5 82 hsa05032:Morphine 5.670103 9.16E-0 4.7458791 11 2.42E-04 addiction 093 5 21 hsa04912:GnRH signaling 5.670103 9.16E-0 4.7458791 11 2.42E-04 pathway 093 5 21 hsa04930:Type II diabetes 4.123711 1.82E-0 6.5435606 8 4.75E-04 mellitus 34 4 06 hsa04913:Ovarian 4.123711 2.07E-0 6.4100185 8 5.36E-04 steroidogenesis 34 4 53 hsa05211:Renal cell 4.639175 2.12E-0 5.4361888 9 5.42E-04 carcinoma 258 4 11 hsa04970:Salivary secretion 10 5.154639 3.00E-0 4.5652748 7.57E-04 175 4 41 hsa04261:Adrenergic 6.701030 3.08E-0 3.4958748 13 7.67E-04 signaling in cardiomyocytes 928 4 44 hsa04728:Dopaminergic 6.185567 3.74E-0 3.6807528 12 9.22E-04 synapse 01 4 41 hsa05033:Nicotine 3.608247 4.54E-0 6.8707386 0.00110 7 addiction 423 4 36 7733 hsa04150:mTOR signaling 4.123711 5.99E-0 5.4153605 0.00144 8 pathway 34 4 02 4647 hsa04921:Oxytocin 6.701030 6.32E-0 3.2303653 0.00150 13 signaling pathway 928 4 62 6912 hsa05204:Chemical 4.639175 8.84E-0 4.4169034 0.00208 9 carcinogenesis 258 4 09 3168

Supplementary Table S4 TBI specific proteins Gene Protein name Gene name Protein name name Nitric oxide synthase, NOS2 Ornithine decarboxylase ODC1 inducible Prostaglandin G/H Xanthine PTGS1 XDH synthase 1 dehydrogenase/oxidase Dopamine D1 receptor DRD1 Caspase-8 CASP8 Muscarinic acetylcholine CHRM3 DNA topoisomerase 1 TOP1 receptor M3 RAF proto-oncogene Thrombin F2 serine/threonine-protein RAF1 kinase Potassium voltage-gated Superoxide dismutase KCNH2 SOD1 channel subfamily H [Cu-Zn] member 2 Muscarinic acetylcholine CHRM1 Protein kinase C alpha type PRKCA receptor M1 Estrogen receptor ESR1 Interstitial collagenase MMP1 Hypoxia-inducible factor Androgen receptor AR HIF1A 1-alpha Signal transducer and Beta-1 adrenergic ADRB1 activator of transcription STAT1 receptor 1-alpha/beta Sodium channel protein SCN5A Protein CBFA2T1 RUNX1T1 type 5 subunit alpha Probable E3 Peroxisome proliferator PPARG ubiquitin-protein ligase HERC5 activated receptor gamma HERC5 Cell division control protein Coagulation factor Xa F10 CDK1 2 homolog Muscarinic acetylcholine 78 kDa glucose-regulated CHRM5 HSPA5 receptor M5 protein Prostaglandin G/H Receptor tyrosine-protein PTGS2 ERBB2 synthase 2 kinase erbB-2 Peroxisome Nitric-oxide synthase, NOS3 proliferator-activated PPARG endothelial receptor gamma Alpha-2C adrenergic ADRA2C Acetyl-CoA carboxylase 1 ACACA receptor Muscarinic acetylcholine CHRM4 Heme oxygenase 1 HMOX1 receptor M4 Retinoic acid receptor RXRA Cytochrome P450 3A4 CYP3A4 RXR-alpha Delta-type opioid receptor OPRD1 Cytochrome P450 1A2 CYP1A2 CGMP-inhibited 3',5'-cyclic PDE3A Caveolin-1 CAV1 phosphodiesterase A 5-hydroxytryptamine 2A Myc proto-oncogene HTR2A MYC receptor protein Alpha-1A adrenergic ADRA1A Tissue factor F3 receptor Muscarinic acetylcholine Gap junction alpha-1 CHRM2 GJA1 receptor M2 protein Alpha-1B adrenergic ADRA1B Cytochrome P450 1A1 CYP1A1 receptor Sodium-dependent Intercellular adhesion SLC6A3 ICAM1 dopamine transporter molecule 1 Beta-2 adrenergic ADRB2 Interleukin-1 beta IL1B receptor Alpha-1D adrenergic ADRA1D C-C motif chemokine 2 CCL2 receptor Sodium-dependent SLC6A4 E-selectin SELE serotonin transporter Vascular cell adhesion Estrogen receptor beta ESRRB VCAM1 protein 1 Gamma-aminobutyric Prostaglandin E2 receptor acid receptor subunit GABRA1 PTGER3 EP3 subtype alpha-1 Dipeptidyl peptidase IV DPP4 Interleukin-8 CXCL8 Mitogen-activated protein MAPK14 Protein kinase C beta type PRKCB kinase 14 Glycogen synthase GSK3B Baculoviral IAP BIRC5 kinase-3 beta repeat-containing protein 5 Heat shock protein HSP HSP 90 Dual oxidase 2 DUOX2 90 Cell division protein Nitric oxide synthase, CDK2 NOS3 kinase 2 endothelial Serine/threonine-protein CHEK1 Heat shock protein beta-1 HSPB1 kinase Chk1 mRNA of PKA Catalytic Transforming growth factor PRKACA TGFB1 Subunit C-alpha beta-1 Retinoic acid receptor RXRB Estrogen sulfotransferase SULT1E1 RXR-beta Maltase-glucoamylase, Trypsin-1 PRSS1 MGAM intestinal Proto-oncogene serine/threonine-protein PIM1 Interleukin-2 IL2 kinase Pim-1 Nuclear receptor subfamily Cyclin-A2 CCNA2 NR2C2 1 group I member 2 Nuclear receptor NCOA2 Cytochrome P450 1B1 CYP1B1 coactivator 2 Calcium-activated G2/mitotic-specific potassium channel subunit KCNMA1 CCNB1 cyclin-B1 alpha 1 Tissue-type plasminogen Calmodulin CALM PLAT activator Nitric oxide synthase, NOS2 Thrombomodulin THBD inducible Prostaglandin G/H Plasminogen activator SERPINE PTGS1 synthase 1 inhibitor 1 1 Muscarinic acetylcholine CHRM1 Collagen alpha-1(I) chain COL1A1 receptor M1 Estrogen receptor ESR2 Interferon gamma IFNG Arachidonate Androgen receptor AR ALOX5 5-lipoxygenase Phosphatidylinositol-3,4,5-t Peroxisome proliferator risphosphate 3-phosphatase PPARG PTEN activated receptor gamma and dual-specificity protein phosphatase PTEN Prostaglandin G/H PTGS2 Interleukin-1 alpha IL1A synthase 2 Retinoic acid receptor RXRA Myeloperoxidase MPO RXR-alpha CGMP-inhibited DNA topoisomerase 3',5'-cyclic PDE3A TOP2A 2-alpha phosphodiesterase A Alpha-1A adrenergic ADRA1A Neutrophil cytosol factor 1 NCF1 receptor Sodium-dependent ATP-binding cassette SLC6A3 ABCG2 dopamine transporter sub-family G member 2 Beta-2 adrenergic ADRB2 Hyaluronan synthase 2 HAS2 receptor Sodium-dependent SLC6A4 Glutathione S-transferase P GSTP1 serotonin transporter Nuclear factor erythroid Estrogen receptor beta MAOB NFE2L2 2-related factor 2 NAD(P)H dehydrogenase Dipeptidyl peptidase IV DPP4 NQO1 [quinone] 1 Mitogen-activated protein MAPK14 Poly [ADP-ribose] PARP1 kinase 14 polymerase 1 Glycogen synthase GSK3B Aryl hydrocarbon receptor AHR kinase-3 beta 26S proteasome Heat shock protein HSP HSP90 non-ATPase regulatory PSMD3 90 subunit 3 Solute carrier family 2, Cell division protein CDK2 facilitated glucose SLC2A4 kinase 2 transporter member 4 Amine oxidase PKIA Collagen alpha-1(III) chain COL3A1 [flavin-containing] B Serine/threonine-protein CHEK1 DNA gyrase subunit B GYRB kinase Chk1 mRNA of PKA Catalytic PRKACA C-X-C motif chemokine 11 CXCL11 Subunit C-alpha Trypsin-1 PRSS1 C-X-C motif chemokine 2 CXCL2 Proto-oncogene DDB1- and serine/threonine-protein PIM1 DCAF5 CUL4-associated factor 5 kinase Pim-1 Nuclear receptor subfamily Cyclin-A2 CCNA2 NR1I3 1 group I member 3 Serine/threonine-protein Calmodulin CALM CHEK2 kinase Chk2 cAMP-dependent protein ACHE Insulin receptor INSR kinase inhibitor alpha Thrombin F2 Claudin-4 CLDN4 Peroxisome Nitric-oxide synthase, NOS3 proliferator-activated PPARA endothelial receptor alpha Peroxisome Acetylcholinesterase LACTB2 proliferator-activated PPARD receptor delta Beta-lactamase JUN Heat shock factor protein 1 HSF1 Transcription factor AP-1 IL4 C-reactive protein CRP Peroxisome proliferator-activated PPARG C-X-C motif chemokine 10 CXCL10 receptor gamma Inhibitor of nuclear factor Interleukin-4 SIRT1 kappa-B kinase subunit CHUK alpha NAD-dependent ATP5F1B Osteopontin SPP1 deacetylase sirtuin-1 ATP synthase subunit Runt-related transcription MT-ND6 RUNX2 beta, mitochondrial factor 2 Ras association NADH-ubiquinone HSD3B2 domain-containing protein RASSF1 oxidoreductase chain 6 1 3 beta-hydroxysteroid dehydrogenase/Delta HSD3B1 Transcription factor E2F1 E2F1 5-->4-isomerase type 2 3 beta-hydroxysteroid dehydrogenase/Delta HTR3A Transcription factor E2F2 E2F2 5-->4-isomerase type 1 Cell division protein CDK2 Prostatic acid phosphatase ACPP kinase 2 Thrombin F2 Cathepsin D CTSD Glycogen synthase Insulin-like growth GSK3B IGFBP3 kinase-3 beta factor-binding protein 3 Nitric oxide synthase, NOS2 Insulin-like growth factor II IGF2 inducible Prostaglandin G/H PTGS1 CD40 ligand CD40LG synthase 1 Muscarinic acetylcholine Interferon regulatory factor CHRNA7 IRF1 receptor M3 1 Receptor tyrosine-protein Thrombin F2 ERBB3 kinase erbB-3 Muscarinic acetylcholine Serum CHRM1 PON1 receptor M1 paraoxonase/arylesterase 1 Type I iodothyronine Estrogen receptor ESR1 DIO1 deiodinase Procollagen Sodium channel protein SCN5A C-endopeptidase enhancer PCOLCE type 5 subunit alpha 1 Prostaglandin G/H Puromycin-sensitive PTGS2 NPEPPS synthase 2 aminopeptidase 5-hydroxytryptamine NCOA1 Hexokinase-2 HK2 receptor 3A Retinoic acid receptor PGR Homeobox protein Nkx-3.1 NKX3-1 RXR-alpha Ras GTPase-activating Acetylcholinesterase LACTB2 RASA1 protein 1 Alpha-1B adrenergic ADRA1B Peroxidase C1A PRXC1A receptor Beta-2 adrenergic Glutathione S-transferase ADRB2 GSTM1 receptor Mu 1 Alpha-1D adrenergic Glutathione S-transferase ADRA1D GSTM2 receptor Mu 2 Gamma-aminobutyric Nitric oxide synthase, acid receptor subunit GABRA1 NOS2 inducible alpha-1 Heat shock protein HSP Prostaglandin G/H synthase HSP 90 PTGS1 90 1 Neuronal acetylcholine receptor protein, alpha-7 OPRM1 Androgen receptor AR chain Peroxisome proliferator Trypsin-1 PRSS1 PPARG activated receptor gamma Nuclear receptor Prostaglandin G/H synthase NCOA2 PTGS2 coactivator 2 2 Nuclear receptor NCOA1 Heat shock protein HSP 90 HSP 90 coactivator 1 Phosphatidylinositol-4,5-bis phosphate 3-kinase Calmodulin CALM PIK3CG catalytic subunit, gamma isoform Muscarinic acetylcholine mRNA of PKA Catalytic CHRM4 PRKACA receptor M4 Subunit C-alpha Nuclear receptor Progesterone receptor PGR NCOA2 coactivator 2 Nitric oxide synthase, NOS2 Dipeptidyl peptidase IV DPP4 inducible Prostaglandin G/H PTGS1 Trypsin-1 PRSS1 synthase 1 Muscarinic acetylcholine CHRNA7 Progesterone receptor PGR receptor M3 Thrombin F2 Thrombin F2 Muscarinic acetylcholine Muscarinic acetylcholine CHRM1 CHRM1 receptor M1 receptor M1 Nitric-oxide synthase, Estrogen receptor ESR1 NOS3 endothelial Beta-1 adrenergic Gamma-aminobutyric-acid ADRB1 GABRA2 receptor receptor alpha-2 subunit Sodium channel protein SCN5A Acetylcholinesterase LACTB2 type 5 subunit alpha Prostaglandin G/H Sodium-dependent PTGS2 SLC6A2 synthase 2 noradrenaline transporter Nitric-oxide synthase, Muscarinic acetylcholine NOS3 CHRM2 endothelial receptor M2 5-hydroxytryptamine Alpha-1B adrenergic HTR3A ADRA1B receptor 3A receptor Alpha-2C adrenergic Gamma-aminobutyric acid ADRA2C GABRA1 receptor receptor subunit alpha-1 Retinoic acid receptor RXRA DNA topoisomerase II TOP2 RXR-alpha Acetylcholinesterase LACTB2 Coagulation factor VII F7 CGMP-inhibited 3',5'-cyclic PDE3A Calmodulin CALM phosphodiesterase A Alpha-1B adrenergic ADRA1B Transcription factor p65 RELA receptor Beta-2 adrenergic Inhibitor of nuclear factor ADRB2 IKBKB receptor kappa-B kinase subunit beta RAC-alpha Alpha-1D adrenergic ADRA1D serine/threonine-protein AKT1 receptor kinase Mu-type opioid receptor OPRM1 Apoptosis regulator Bcl-2 BCL2 Gamma-aminobutyric acid receptor subunit GABRA1 Apoptosis regulator BAX BAX alpha-1 Trypsin-1 PRSS1 Tumor necrosis factor TNF Nuclear receptor NCOA2 Transcription factor AP-1 IL4 coactivator 2 Activator of 90 kDa heat Calmodulin CALM shock protein ATPase AHSA1 homolog 1 Nitric oxide synthase, NOS2 Caspase-3 CASP3 inducible Prostaglandin G/H Mitogen-activated protein PTGS1 MAPK8 synthase 1 kinase 8 Xanthine Androgen receptor AR XDH dehydrogenase/oxidase Sodium channel protein SCN5A Interstitial collagenase MMP1 type 5 subunit alpha Signal transducer and Prostaglandin G/H PTGS2 activator of transcription STAT1 synthase 2 1-alpha/beta Cell division control protein Estrogen receptor beta MAOB CDK1 2 homolog Peroxisome Dipeptidyl peptidase IV DPP4 proliferator-activated PPARG receptor gamma Heat shock protein HSP HSP 90 Heme oxygenase 1 HMOX1 90 Cell division protein CDK2 Cytochrome P450 3A4 CYP3A4 kinase 2 Serine/threonine-protein CHEK1 Cytochrome P450 1A2 CYP1A2 kinase Chk1 Trypsin-1 PRSS1 Cytochrome P450 1A1 CYP1A1 Nuclear receptor Intercellular adhesion NCOA2 ICAM1 coactivator 2 molecule 1 Calmodulin CALM E-selectin SELE Nitric oxide synthase, Vascular cell adhesion NOS2 VCAM1 inducible protein 1 Prostaglandin G/H Nuclear receptor subfamily PTGS1 NR2C2 synthase 1 1 group I member 2 Estrogen receptor ESR1 Cytochrome P450 1B1 CYP1B1 Arachidonate Androgen receptor AR ALOX5 5-lipoxygenase Peroxisome proliferator PPARG Hyaluronan synthase 2 HAS2 activated receptor gamma Prostaglandin G/H Prostaglandin G/H synthase PTGS2 PTGS2 synthase 2 2 mRNA of Protein-tyrosine Retinoic acid receptor phosphatase, PTPN1 RXRA RXR-alpha non-receptor type 1 Estrogen receptor beta MAOB Heat shock protein HSP 90 HSP 90 Dipeptidyl peptidase IV DPP4 Trypsin-1 PRSS1 Mitogen-activated protein MAPK14 Progesterone receptor PGR kinase 14 Glycogen synthase Nuclear receptor GSK3B NCOA2 kinase-3 beta coactivator 2 Heat shock protein HSP Muscarinic acetylcholine HSP 90 CHRNA7 90 receptor M3 Cell division protein Muscarinic acetylcholine CDK2 CHRM1 kinase 2 receptor M1 Phosphatidylinositol-4,5- bisphosphate 3-kinase Gamma-aminobutyric-acid PIK3CG GABRA2 catalytic subunit, gamma receptor alpha-2 subunit isoform mRNA of PKA Catalytic Gamma-aminobutyric-acid PRKACA GABRA3 Subunit C-alpha receptor alpha-3 subunit Muscarinic acetylcholine Trypsin-1 PRSS1 CHRM2 receptor M2 Proto-oncogene Alpha-1B adrenergic serine/threonine-protein PIM1 ADRA1B receptor kinase Pim-1 Gamma-aminobutyric acid Cyclin-A2 CCNA2 GABRA1 receptor subunit alpha-1 Nuclear receptor NCOA2 Glutamate receptor 2 GRIA2 coactivator 2 Gamma-aminobutyric-acid Calmodulin CALM GABRA6 receptor subunit alpha-6 Glycogen phosphorylase, Gamma-aminobutyric-acid PYGM GABRA5 muscle form receptor alpha-5 subunit Peroxisome proliferator PPARD Ig gamma-1 chain C region IGHG1 activated receptor delta Serine/threonine-protein CHEK1 Alcohol dehydrogenase 1B ALDH1B1 kinase Chk1 Aldose reductase AKR1B1 Alcohol dehydrogenase 1C ALDH3A1 Nuclear receptor NCOA1 Lysozyme LYZ1 coactivator 1 Coagulation factor VII F7 Nicotinate-nucleotide--dime COBT thylbenzimidazole phosphoribosyltransferase Prostaglandin G/H synthase Thrombin F2 PTGS1 1 Nitric-oxide synthase, Sodium channel protein NOS3 SCN5A endothelial type 5 subunit alpha Prostaglandin G/H synthase Acetylcholinesterase LACTB2 PTGS2 2 Gamma-aminobutyric Retinoic acid receptor acid receptor subunit GABRA1 RXRA RXR-alpha alpha-1 Amine oxidase CGMP-inhibited 3',5'-cyclic PKIA PDE3A [flavin-containing] B phosphodiesterase A Sodium-dependent Glutamate receptor 2 GRIA2 SLC6A2 noradrenaline transporter Cytochrome P450-cam CAMC Cytochrome P450-cam CYP21A2 Prostaglandin G/H synthase Transcription factor p65 RELA PTGS2 2 Xanthine XDH DNA topoisomerase II TOP2 dehydrogenase/oxidase Neutrophil cytosol factor Nuclear receptor NCOA1 NCOA2 1 coactivator 2 Oxidized low-density OLR1 Progesterone receptor PGR lipoprotein receptor 1 Prostaglandin G/H synthase DNA topoisomerase II TOP2 PTGS2 2 Nitric oxide synthase, Vascular endothelial NOS2 KDR inducible growth factor receptor 2 Prostaglandin G/H PTGS1 Hepatocyte growth factor MET synthase 1 receptor Estrogen receptor ESR1 Heat shock protein HSP 90 HSP 90 Calcium-activated Androgen receptor AR potassium channel subunit KCNMA1 alpha 1 Peroxisome proliferator Prostaglandin G/H synthase PPARG PTGS1 activated receptor gamma 1 Prostaglandin G/H PTGS2 DNA topoisomerase II TOP2 synthase 2 Retinoic acid receptor RXRA Progesterone receptor PGR RXR-alpha CGMP-inhibited Nuclear receptor 3',5'-cyclic PDE3A NCOA2 coactivator 2 phosphodiesterase A Prostaglandin G/H synthase Estrogen receptor beta MAOB PTGS1 1 Prostaglandin G/H synthase Dipeptidyl peptidase IV DPP4 PTGS2 2 Mitogen-activated protein MAPK14 Heat shock protein HSP 90 HSP 90 kinase 14 Phosphatidylinositol-4,5-bis Glycogen synthase phosphate 3-kinase GSK3B PIK3CG kinase-3 beta catalytic subunit, gamma isoform Potassium voltage-gated Heat shock protein HSP HSP 90 channel subfamily H KCNH2 90 member 2 Cell division protein mRNA of PKA Catalytic CDK2 PRKACA kinase 2 Subunit C-alpha Serine/threonine-protein CHEK1 Dopamine D1 receptor DRD1 kinase Chk1 mRNA of PKA Catalytic Muscarinic acetylcholine PRKACA CHRNA7 Subunit C-alpha receptor M3 Muscarinic acetylcholine Trypsin-1 PRSS1 CHRM1 receptor M1 Proto-oncogene Sodium channel protein serine/threonine-protein PIM1 SCN5A type 5 subunit alpha kinase Pim-1 Gamma-aminobutyric-acid Cyclin-A2 CCNA2 GABRA2 receptor alpha-2 subunit Nuclear receptor Muscarinic acetylcholine NCOA2 CHRM4 coactivator 2 receptor M4 CGMP-inhibited 3',5'-cyclic Calmodulin CALM PDE3A phosphodiesterase A Beta-2 adrenergic 5-hydroxytryptamine 2A ADRB2 HTR2A receptor receptor Prostaglandin G/H Gamma-aminobutyric-acid PTGS1 GABRA5 synthase 1 receptor alpha-5 subunit Alpha-1A adrenergic Androgen receptor AR ADRA1A receptor Peroxisome proliferator Gamma-aminobutyric-acid PPARG GABRA3 activated receptor gamma receptor alpha-3 subunit Prostaglandin G/H Muscarinic acetylcholine PTGS2 CHRM2 synthase 2 receptor M2 Heat shock protein HSP Alpha-1B adrenergic HSP 90 ADRA1B 90 receptor Phosphatidylinositol-4,5- PIK3CG Beta-2 adrenergic receptor ADRB2 bisphosphate 3-kinase catalytic subunit, gamma isoform Nuclear receptor Neuronal acetylcholine NCOA2 CHRNA2 coactivator 2 receptor subunit alpha-2 Sodium-dependent Dipeptidyl peptidase IV DPP4 SLC6A4 serotonin transporter Aldose reductase AKR1B1 Mu-type opioid receptor OPRM1 Gamma-aminobutyric acid Trypsin-1 PRSS1 GABRA1 receptor subunit alpha-1 Neuronal acetylcholine DNA topoisomerase II TOP2 receptor protein, alpha-7 OPRM1 chain Thrombin F2 Cytochrome P450-cam CYP21A2 Potassium voltage-gated channel subfamily H KCNH2 Apoptosis regulator Bcl-2 BCL2 member 2 Sodium channel protein SCN5A Apoptosis regulator BAX BAX type 5 subunit alpha Coagulation factor Xa F10 Caspase-9 CASP9 Beta-2 adrenergic ADRB2 Transcription factor AP-1 IL4 receptor Stromelysin-1 MMP3 Caspase-3 CASP3 mRNA of PKA Catalytic PRKACA Caspase-8 CASP8 Subunit C-alpha Coagulation factor VII F7 Protein kinase C alpha type PRKCA Nitric-oxide synthase, Transforming growth factor NOS3 TGFB1 endothelial beta-1 Retinoic acid receptor Serum RXRA PON1 RXR-alpha paraoxonase/arylesterase 1 Microtubule-associated Acetylcholinesterase LACTB2 MAP2 protein 2 Gamma-aminobutyric acid receptor subunit GABRA1 Progesterone receptor PGR alpha-1 Amine oxidase PKIA Mineralocorticoid receptor NR3C2 [flavin-containing] B Nuclear receptor Transcription factor p65 RELA NCOA2 coactivator 2 Epidermal growth factor EGFR Alcohol dehydrogenase 1C ADH1C receptor RAC-alpha serine/threonine-protein AKT1 Ig gamma-1 chain C region IGHG1 kinase Vascular endothelial Retinoic acid receptor VEGFA RXRA growth factor A RXR-alpha Nuclear receptor G1/S-specific cyclin-D1 CCND1 NCOA1 coactivator 1 Prostaglandin G/H synthase Apoptosis regulator Bcl-2 BCL2 PTGS1 1 Prostaglandin G/H synthase Bcl-2-like protein 1 BCL2L1 PTGS2 2 Alpha-2A adrenergic Proto-oncogene c-Fos FOS ADRA2A receptor Cyclin-dependent kinase Sodium-dependent CDKN1 SLC6A2 inhibitor 1 noradrenaline transporter Eukaryotic translation Sodium-dependent EIF6 SLC6A3 initiation factor 6 dopamine transporter Apoptosis regulator BAX BAX Beta-2 adrenergic receptor ADRB2 Caspase-9 CASP9 Aldose reductase AKR1B1 Urokinase-type Urokinase-type PLAU PLAU plasminogen activator plasminogen activator 72 kDa type IV MMP2 Leukotriene A-4 hydrolase LTA4H collagenase Matrix Amine oxidase MMP9 PKIA metalloproteinase-9 [flavin-containing] B Mitogen-activated protein Amine oxidase MAPK1 MAOA kinase 1 [flavin-containing] A mRNA of PKA Catalytic Interleukin-10 IL10 PRKACA Subunit C-alpha Pro-epidermal growth EGF Chymotrypsinogen B CTRB1 factor Retinoblastoma-associate Muscarinic acetylcholine RB1 CHRNA7 d protein receptor M3 Muscarinic acetylcholine Tumor necrosis factor TNF CHRM1 receptor M1 Transcription factor AP-1 IL4 Beta-1 adrenergic receptor ADRB1 Sodium channel protein Interleukin-6 IL6 SCN5A type 5 subunit alpha Cyclin-dependent kinase 5-hydroxytryptamine 2A inhibitor 2A, isoforms CDKN2A HTR2A receptor 1/2/3 Activator of 90 kDa heat Alpha-1A adrenergic shock protein ATPase AHSA1 ADRA1A receptor homolog 1 Gamma-aminobutyric-acid Caspase-3 CASP3 GABRA3 receptor alpha-3 subunit Cellular tumor antigen TP53 Muscarinic acetylcholine CHRM2 p53 receptor M2 ETS domain-containing Alpha-1B adrenergic ELK1 ADRA1B protein Elk-1 receptor NF-kappa-B inhibitor Gamma-aminobutyric acid NFKBIA GABRA1 alpha receptor subunit alpha-1 Neuronal acetylcholine NADPH--cytochrome POR receptor protein, alpha-7 OPRM1 P450 reductase chain

Supplementary Table S5 89 signal pathways related to AR-RAS for treating TBI Fold Term Count % P-Value Enrichmen Benjamini t 34.37 17.473563 hsa05161:Hepatitis B 11 1.73E-10 2.82E-08 5 22 hsa05145:Toxoplasmosi 19.519774 10 31.25 6.83E-10 5.57E-08 s 01 hsa05200:Pathways in 40.62 7.6191687 13 2.08E-08 1.13E-06 cancer 5 87 13.013182 hsa05152:Tuberculosis 10 31.25 2.50E-08 1.02E-06 67 hsa04066:HIF-1 18.802721 8 25 1.12E-07 3.67E-06 signaling pathway 09 28.12 11.913793 hsa05164:Influenza A 9 3.76E-07 1.02E-05 5 1 hsa04071:Sphingolipid 8 25 4.54E-07 15.355555 1.06E-05 signaling pathway 56 hsa04010:MAPK 9.0326797 10 31.25 5.78E-07 1.18E-05 signaling pathway 39 hsa05223:Non-small 24.678571 6 18.75 2.98E-06 5.40E-05 cell lung cancer 43 hsa04150:mTOR 23.827586 6 18.75 3.56E-06 5.80E-05 signaling pathway 21 hsa05142:Chagas 21.87 15.503205 disease (American 7 3.61E-06 5.34E-05 5 13 trypanosomiasis) 22.290322 hsa04210:Apoptosis 6 18.75 4.97E-06 6.75E-05 58 hsa05210:Colorectal 22.290322 6 18.75 4.97E-06 6.75E-05 cancer 58 hsa04725:Cholinergic 21.87 14.525525 7 5.27E-06 6.61E-05 synapse 5 53 hsa05212:Pancreatic 21.261538 6 18.75 6.29E-06 7.32E-05 cancer 46 hsa04380:Osteoclast 21.87 12.307888 7 1.37E-05 1.49E-04 differentiation 5 04 hsa05205:Proteoglycans 9.2133333 8 25 1.39E-05 1.42E-04 in cancer 33 21.87 12.122807 hsa05160:Hepatitis C 7 1.50E-05 1.44E-04 5 02 hsa04012:ErbB 15.885057 6 18.75 2.64E-05 2.39E-04 signaling pathway 47 hsa05215:Prostate 15.704545 6 18.75 2.79E-05 2.39E-04 cancer 45 hsa04014:Ras signaling 8 25 3.08E-05 8.1533923 2.51E-04 pathway 3 hsa04932:Non-alcoholic 21.87 10.677704 fatty liver disease 7 3.09E-05 2.40E-04 5 19 (NAFLD) hsa04660:T cell 13.417475 receptor signaling 6 18.75 5.96E-05 4.42E-04 73 pathway 13.037735 hsa05146:Amoebiasis 6 18.75 6.85E-05 4.85E-04 85 hsa04668:TNF signaling 13.037735 6 18.75 6.85E-05 4.85E-04 pathway 85 hsa04620:Toll-like 13.037735 receptor signaling 6 18.75 6.85E-05 4.85E-04 85 pathway hsa04931:Insulin 12.796296 6 18.75 7.49E-05 5.08E-04 resistance 3 hsa04020:Calcium 21.87 9.0074487 7 8.04E-05 5.24E-04 signaling pathway 5 9 hsa04919:Thyroid 12.122807 hormone signaling 6 18.75 9.69E-05 6.07E-04 02 pathway hsa04370:VEGF 15.62 18.879781 5 1.11E-04 6.68E-04 signaling pathway 5 42 hsa04650:Natural killer 11.327868 cell mediated 6 18.75 1.34E-04 7.78E-04 85 cytotoxicity 15.62 17.717948 hsa05214:Glioma 5 1.42E-04 7.98E-04 5 72 hsa04728:Dopaminergic 6 18.75 1.68E-04 10.796875 9.10E-04 synapse hsa04664:Fc epsilon RI 15.62 16.936274 5 1.69E-04 8.90E-04 signaling pathway 5 51 hsa04510:Focal 21.87 7.8268608 7 1.75E-04 8.89E-04 adhesion 5 41 15.62 16.220657 hsa05140:Leishmaniasis 5 2.00E-04 9.89E-04 5 28 hsa04261:Adrenergic 9.4657534 0.00148579 signaling in 6 18.75 3.10E-04 25 7 cardiomyocytes hsa05143:African 27.919191 0.00155098 4 12.5 3.33E-04 trypanosomiasis 92 7 hsa04151:PI3K-Akt 5.3410628 0.00197887 8 25 4.37E-04 signaling pathway 02 4 15.62 13.087121 hsa04540:Gap junction 5 4.57E-04 0.00201339 5 21 hsa05231:Choline 15.62 11.402640 0.00330393 5 7.71E-04 metabolism in cancer 5 26 3 hsa05168:Herpes 7.5519125 6 18.75 8.73E-04 0.00364565 simplex infection 68 hsa05206:MicroRNAs in 21.87 5.6573099 0.00404379 7 9.94E-04 cancer 5 42 9 hsa05014:Amyotrophic 0.0011410 18.426666 0.00452886 4 12.5 lateral sclerosis (ALS) 97 67 2 hsa05213:Endometrial 0.0012794 17.717948 0.00495621 4 12.5 cancer 18 72 5 hsa04270:Vascular 15.62 0.0014236 9.6778711 0.00538603 smooth muscle 5 5 82 48 8 contraction hsa04722:Neurotrophin 15.62 0.0014685 9.5972222 5 0.00542938 signaling pathway 5 13 22 hsa04621:NOD-like 0.0015060 16.751515 0.00544439 receptor signaling 4 12.5 24 15 1 pathway hsa04068:FoxO 15.62 0.0022042 8.5945273 0.00778895 5 signaling pathway 5 82 63 6 hsa05321:Inflammatory 14.395833 0.00806398 4 12.5 0.0023319 bowel disease (IBD) 33 2 hsa04910:Insulin 15.62 0.0024541 8.3454106 0.00830949 5 signaling pathway 5 75 28 5 hsa05031:Amphetamine 0.0025467 13.959595 0.00844686 4 12.5 addiction 79 96 8 hsa04662:B cell 0.0028914 0.00939550 receptor signaling 4 12.5 13.352657 92 3 pathway hsa04917:Prolactin 0.0031365 12.976525 0.00999017 4 12.5 signaling pathway 49 82 4 hsa05220:Chronic 0.0032637 12.796296 0.01019494 4 12.5 myeloid leukemia 31 3 7 hsa04921:Oxytocin 15.62 0.0040021 7.2890295 0.01225734 5 signaling pathway 5 15 36 5 hsa04022:cGMP-PKG 15.62 0.0047735 6.9377510 0.01433969 5 signaling pathway 5 35 04 8 hsa05010:Alzheimer's 15.62 0.0049810 6.8551587 0.01468990 5 disease 5 37 3 4 hsa04666:Fc gamma 0.0050413 10.968253 0.01460350 R-mediated 4 12.5 99 97 4 phagocytosis hsa04350:TGF-beta 0.0050413 10.968253 0.01460350 4 12.5 signaling pathway 99 97 4 hsa04970:Salivary 0.0053843 10.713178 0.01532051 4 12.5 secretion 97 29 7 hsa04912:GnRH 0.0063025 10.124542 0.01761152 4 12.5 signaling pathway 71 12 3 hsa04062:Chemokine 15.62 0.0071289 6.1917562 0.01957184 5 signaling pathway 5 99 72 4 hsa05169:Epstein-Barr 15.62 0.0076782 6.0614035 0.02072205 5 virus infection 5 62 09 7 hsa04915:Estrogen 0.0079566 9.3063973 0.02111992 4 12.5 signaling pathway 12 06 9 hsa04916:Melanogenesi 0.0081797 9.2133333 0.02136171 4 12.5 s 19 33 5 hsa04015:Rap1 15.62 0.0108472 5.4841269 0.02782407 5 signaling pathway 5 76 84 8 hsa04726:Serotonergic 0.0108799 0.02747723 4 12.5 8.3003003 synapse 79 1 hsa04960:Aldosterone-r 0.0114478 17.717948 0.02846040 egulated sodium 3 9.375 42 72 2 reabsorption hsa05219:Bladder 0.0126029 16.853658 0.03083776 3 9.375 cancer 47 54 9 hsa04930:Type II 0.0170259 14.395833 0.04091726 3 9.375 diabetes mellitus 18 33 4 0.0176784 6.9273182 0.04185412 hsa05162:Measles 4 12.5 13 96 5 0.0177046 14.102040 hsa05144:Malaria 3 9.375 0.04132073 52 82 hsa05166:HTLV-I 15.62 0.0210824 4.4986979 0.04840608 5 infection 5 59 17 2 0.0212675 12.796296 0.04815409 hsa05134:Legionellosis 3 9.375 23 3 3 hsa05221:Acute myeloid 0.0227697 12.339285 0.05080799 3 9.375 leukemia 75 71 3 hsa04730:Long-term 0.0259021 11.516666 0.05691471 3 9.375 depression 59 67 6 hsa05230:Central 0.0291999 0.06319166 carbon metabolism in 3 9.375 10.796875 56 1 cancer hsa05211:Renal cell 0.0300495 10.630769 0.06415837 3 9.375 carcinoma 46 23 8 hsa04720:Long-term 0.0309090 10.469696 0.06512065 3 9.375 potentiation 07 97 8 hsa05120:Epithelial cell signaling in 0.0317782 10.313432 0.06607851 3 9.375 Helicobacter pylori 48 84 8 infection hsa04610:Complement 0.0335457 10.014492 and coagulation 3 9.375 0.06882189 06 75 cascades hsa04622:RIG-I-like 0.0344437 9.8714285 0.06976704 receptor signaling 3 9.375 42 71 4 pathway hsa04920:Adipocytokine 0.0344437 9.8714285 0.06976704 3 9.375 signaling pathway 42 71 4 0.0353511 9.7323943 0.07070777 hsa05218:Melanoma 3 9.375 97 66 1 hsa04520:Adherens 0.0353511 9.7323943 0.07070777 3 9.375 junction 97 66 1 0.0390734 9.2133333 0.07707438 hsa05133:Pertussis 3 9.375 35 33 7 hsa04911:Insulin 0.0489957 8.1294117 0.09503661 3 9.375 secretion 22 65 4 hsa05222:Small cell 0.0489957 8.1294117 0.09503661 3 9.375 lung cancer 22 65 4