doi:10.48130/targetome-0025-0009

[1]

Chen H, Zhou Y, Hao H, Xiong J. 2024. Emerging mechanisms of non-alcoholic steatohepatitis and novel drug therapies. Chinese Journal of Natural Medicines 22:724−745

doi: 10.1016/S1875-5364(24)60690-4

[2]

Loomba R, Friedman SL, Shulman GI. 2021. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell 184:2537−2564

doi: 10.1016/j.cell.2021.04.015

[3]

Friedman SL, Pinzani M. 2022. Hepatic fibrosis 2022: unmet needs and a blueprint for the future. Hepatology 75:473−488

doi: 10.1002/hep.32285

[4]

Kisseleva T, Brenner D. 2021. Molecular and cellular mechanisms of liver fibrosis and its regression. Nature Reviews Gastroenterology & Hepatology 18:151−66

doi: 10.1038/s41575-020-00372-7

[5]

Horn P, Tacke F. 2024. Metabolic reprogramming in liver fibrosis. Cell Metabolism 36:1439−1455

doi: 10.1016/j.cmet.2024.05.003

[6]

Tsuchida T, Friedman SL. 2017. Mechanisms of hepatic stellate cell activation. Nature Reviews Gastroenterology & Hepatology 14:397−411

doi: 10.1038/nrgastro.2017.38

[7]

Dufour JF, Caussy C, Loomba R. 2020. Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges. Gut 69:1877−1884

doi: 10.1136/gutjnl-2019-319104

[8]

Chen Z, Zhou J, Zheng X, Xie H, Hao H. 2025. Metabolic insights into gut microbiota in the pharmacology of natural medicines. Chinese Journal of Natural Medicines 23:158−168

doi: 10.1016/S1875-5364(25)60820-X

[9]

Li H, Guan T, Qin S, Xu Q, Yin L, et al. 2023. Natural products in pursuing novel therapies of nonalcoholic fatty liver disease and steatohepatitis. Drug Discovery Today 28:103471

doi: 10.1016/j.drudis.2022.103471

[10]

Li H. 2020. Advances in anti hepatic fibrotic therapy with Traditional Chinese Medicine herbal formula. Journal of Ethnopharmacology 251:112442

doi: 10.1016/j.jep.2019.112442

[11]

Abenavoli L, Capasso R, Milic N, Capasso F. 2010. Milk thistle in liver diseases: past, present, future. Phytotherapy Research 24:1423−1432

doi: 10.1002/ptr.3207

[12]

Yan W, Wang D, Wan N, Wang S, Shao C, et al. 2022. Living cell-target responsive accessibility profiling reveals silibinin targeting ACSL4 for combating ferroptosis. Analytical Chemistry 94:14820−14826

doi: 10.1021/acs.analchem.2c03515

[13]

Kim M, Yang SG, Kim JM, Lee JW, Kim YS, et al. 2012. Silymarin suppresses hepatic stellate cell activation in a dietary rat model of non-alcoholic steatohepatitis: analysis of isolated hepatic stellate cells. International Journal of Molecular Medicine 30:473−479

doi: 10.3892/ijmm.2012.1029

[14]

Angulo P, Patel T, Jorgensen RA, Therneau TM, Lindor KD. 2000. Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 32:897−900

doi: 10.1053/jhep.2000.18663

[15]

Cui S, Hu H, Chen A, Cui M, Pan X, et al. 2023. SIRT1 activation synergizes with FXR agonism in hepatoprotection via governing nucleocytoplasmic shuttling and degradation of FXR. Acta Pharmaceutica Sinica B 13:559−576

doi: 10.1016/j.apsb.2022.08.019

[16]

Wang K, Zhang P, Sun H, Cui S, Ao L, et al. 2024. Dual-function natural products: farnesoid X receptor agonist/inflammation inhibitor for metabolic dysfunction-associated steatotic liver disease therapy. Chinese Journal of Natural Medicines 22:965−976

doi: 10.1016/S1875-5364(24)60706-5

[17]

Venkatesan T, Choi YW, Kim YK. 2019. Effect of an extraction solvent on the antioxidant quality of Pinus densiflora needle extract. Journal of Pharmaceutical Analysis 9:193−200

doi: 10.1016/j.jpha.2019.03.005

[18]

Wang H, Yan T, Xie Y, Zhao M, Che Y, et al. 2015. Mechanism-based inhibitory and peroxisome proliferator-activated receptor α-dependent modulating effects of silybin on principal hepatic drug-metabolizing enzymes. Drug Metabolism and Disposition 43:444−454

doi: 10.1124/dmd.114.061622

[19]

Wang H, Ge C, Zhou J, Guo Y, Cui S, et al. 2018. Noncanonical farnesoid X receptor signaling inhibits apoptosis and impedes liver fibrosis. eBioMedicine 37:322−333

doi: 10.1016/j.ebiom.2018.10.028

[20]

Trandafir LM, Frasinariu OE, Leon-Constantin MM, Chiriac Ş, Trandafirescu MF, et al. 2020. Pediatric nonalcoholic fatty liver disease – a changing diagnostic paradigm. Romanian Journal of Morphology and Embryology 61:1023−1031

doi: 10.47162/rjme.61.4.04

[21]

Zhang N, Fu JN, Chou TC. 2015. Synergistic combination of microtubule targeting anticancer fludelone with cytoprotective panaxytriol derived from panax ginseng against MX-1 cells in vitro: experimental design and data analysis using the combination index method. American Journal of Cancer Research 6:97−104

[22]

Cui S, Pan XJ, Ge CL, Guo YT, Zhang PF, et al. 2021. Silybin alleviates hepatic lipid accumulation in methionine-choline deficient diet-induced nonalcoholic fatty liver disease in mice via peroxisome proliferator-activated receptor α. Chinese Journal of Natural Medicines 19:401−411

doi: 10.1016/S1875-5364(21)60039-0

[23]

Yang X, Lou Y, Li H, Ma Y, Wang Z, et al. 2025. Silybin inhibits succinate production and secretion in hepatocytes to reverse liver fibrosis. Archives of Pharmacal Research 48:782−797

doi: 10.1007/s12272-025-01560-2

[24]

Pan F, Chernew ME, Fendrick AM. 2008. Impact of fixed-dose combination drugs on adherence to prescription medications. Journal of General Internal Medicine 23:611−614

doi: 10.1007/s11606-008-0544-x

[25]

Monga SP. 2015. β-Catenin signaling and roles in liver homeostasis, injury, and tumorigenesis. Gastroenterology 148:1294−1310

doi: 10.1053/j.gastro.2015.02.056

[26]

Zamani M, Alizadeh-Tabari S, Ajmera V, Singh S, Murad MH, et al. 2025. Global prevalence of advanced liver fibrosis and cirrhosis in the general population: a systematic review and meta-analysis. Clinical Gastroenterology and Hepatology 23:1123−1134

doi: 10.1016/j.cgh.2024.08.020

[27]

Benesic A, Jalal K, Gerbes AL. 2019. Acute liver failure during pirfenidone treatment triggered by co-medication with esomeprazole. Hepatology 70:1869−1871

doi: 10.1002/hep.30684

[28]

Anstee QM, Lucas KJ, Francque S, Abdelmalek MF, Sanyal AJ, et al. 2023. Tropifexor plus cenicriviroc combination versus monotherapy in nonalcoholic steatohepatitis: results from the phase 2b TANDEM study. Hepatology 78:1223−1239

doi: 10.1097/HEP.0000000000000439

[29]

Loomba R, Noureddin M, Kowdley KV, Kohli A, Sheikh A, et al. 2021. Combination therapies including cilofexor and firsocostat for bridging fibrosis and cirrhosis attributable to NASH. Hepatology 73:625−643

doi: 10.1002/hep.31622

[30]

Zhou J, Cui S, He Q, Guo Y, Pan X, et al. 2020. SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis. Nature Communications 11:240

doi: 10.1038/s41467-019-14138-6

[31]

Zhou J, Huang N, Guo Y, Cui S, Ge C, et al. 2019. Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis. Acta Pharmaceutica Sinica B 9:526−536

doi: 10.1016/j.apsb.2018.11.004

[32]

Yan T, Yan N, Wang P, Xia Y, Hao H, et al. 2020. Herbal drug discovery for the treatment of nonalcoholic fatty liver disease. Acta Pharmaceutica Sinica B 10:3−18

doi: 10.1016/j.apsb.2019.11.017

[33]

Li Y, Lu Y, Nian M, Sheng Q, Zhang C, et al. 2023. Therapeutic potential and mechanism of Chinese herbal medicines in treating fibrotic liver disease. Chinese Journal of Natural Medicines 21:643−657

doi: 10.1016/S1875-5364(23)60443-1

[34]

Yan T, Wang H, Cao L, Wang Q, Takahashi S, et al. 2018. Glycyrrhizin alleviates nonalcoholic steatohepatitis via modulating bile acids and meta-inflammation. Drug Metabolism and Disposition 46:1310−1319

doi: 10.1124/dmd.118.082008

[35]

Zeng J, Jia X. 2025. Quantifying compatibility mechanisms in traditional Chinese medicine with interpretable graph neural networks. Journal of Pharmaceutical Analysis 15:101342

doi: 10.1016/j.jpha.2025.101342

[36]

Benkel T, Zimmermann M, Zeiner J, Bravo S, Merten N, et al. 2022. How carvedilol activates β2-adrenoceptors. Nature Communications 13:7109

doi: 10.1038/s41467-022-34765-w

[37]

Turco L, Reiberger T, Vitale G, La Mura V. 2023. Carvedilol as the new non-selective beta-blocker of choice in patients with cirrhosis and portal hypertension. Liver International 43:1183−1194

doi: 10.1111/liv.15559

[38]

Xi Y, Li Y, Xu P, Li S, Liu Z, et al. 2021. The anti-fibrotic drug pirfenidone inhibits liver fibrosis by targeting the small oxidoreductase glutaredoxin-1. Science Advances 7:eabg9241

doi: 10.1126/sciadv.abg9241

[39]

He C, Wang W, Wei G, Wang Y, Wei Y, et al. 2023. Sodium alginate combined with oxymatrine ameliorates CCl₄-induced chemical hepatic fibrosis in mice. International Immunopharmacology 125:111144

doi: 10.1016/j.intimp.2023.111144

[40]

Ciardullo S, Perseghin G. 2021. Statin use is associated with lower prevalence of advanced liver fibrosis in patients with type 2 diabetes. Metabolism 121:154752

doi: 10.1016/j.metabol.2021.154752

[41]

Perugorria MJ, Olaizola P, Labiano I, Esparza-Baquer A, Marzioni M, et al. 2019. Wnt-β-catenin signalling in liver development, health and disease. Nature Reviews Gastroenterology & Hepatology 16:121−136

doi: 10.1038/s41575-018-0075-9

[42]

Wang F, Chen L, Kong D, Zhang X, Xia S, et al. 2024. Canonical Wnt signaling promotes HSC glycolysis and liver fibrosis through an LDH-A/HIF-1α transcriptional complex. Hepatology 79:606−623

doi: 10.1097/HEP.0000000000000569

[43]

Yu P, Yao J, Zhang L, Wang Y, Lu X, et al. 2025. TSZAF monomer combination downregulates the Wnt/β-catenin signaling pathway and inhibits neutrophil recruitment to prevent lung cancer metastasis. Chinese Journal of Natural Medicines 23:1069−1079

doi: 10.1016/S1875-5364(25)60973-3

[44]

Xiong WJ, Hu LJ, Jian YC, Wang LJ, Jiang M, et al. 2012. Wnt5a participates in hepatic stellate cell activation observed by gene expression profile and functional assays. World Journal of Gastroenterology 18:1745−1752

doi: 10.3748/wjg.v18.i15.1745

[45]

Jiang F, Parsons CJ, Stefanovic B. 2006. Gene expression profile of quiescent and activated rat hepatic stellate cells implicates Wnt signaling pathway in activation. Journal of Hepatology 45:401−409

doi: 10.1016/j.jhep.2006.03.016

[46]

Hao H, Kirchhoff F. 2025. Navigating drug discovery with Targetome. Targetome 1:e001

doi: 10.48130/targetome-0025-0001

[47]

Liu P, Huang F, Zheng X, Hao H. 2025. Targetome-guided combination drug discovery as next-generation therapeutics. Targetome 1:e002

doi: 10.48130/targetome-0025-0002