Research progress on pathogenesis and drug intervention of alcoholic liver disease

doi:10.12092/j.issn.1009-2501.2026.03.013

Abstract

Abstract:

Alcoholic liver disease (ALD) is a disease of the liver that results from prolonged and heavy drinking, which is initially manifested as a fatty liver, and then develops into hepatitis, cirrhosis, and even hepatocellular carcinoma. The pathogenesis of ALD is characterized by oxidative stress, immune inflammation, gut-hepatic axis, apoptosis, and autophagy induced by regulatory factors such as acetaldehyde dehydrogenase 2 (ALDH2), nuclear factor-κB (NF-κB), and farnesol X receptor (FXR). This article takes regulatory factors as the entry point to summarize drugs such as the NF-κB inhibitor ergacurone, the FXR agonist INT-787, and the PPARα agonist fenofibrate, and explores the current research status from broad treatment to targeted precision treatment. The aim is to gain a deeper understanding of the pathogenesis of ALD and provide a basic information for the prevention and control research of ALD and targeted drug intervention.

Key words: alcoholic liver disease, pathogenesis, regulatory factor, pharmacotherapy, targeted therapy

CLC Number:

R575.5

Yuxiu ZHANG, Bo HE, Lijun ZHANG, Le JI, Zhuang MA, Hongxing ZHENG, Shanshan QI. Research progress on pathogenesis and drug intervention of alcoholic liver disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(3): 409-419.

Figures/Tables 3

References 71

1	郑红星, 冀乐, 祁珊珊. 微生物-肠-肝轴与酒精性肝病及其营养干预研究进展[J]. 食品科学, 2024, 45 (20): 366- 375. doi: 10.7506/spkx1002-6630-20231226-223
2	Xiao J, Wang F, Yuan Y, et al. Epidemiology of liver diseases: global disease burden and forecasted research trends[J]. Sci China Life Sci, 2024, 68 (2): 1- 17.
3	Wu X, Fan X, Miyata T, et al. Recent advances in understanding of pathogenesis of alcohol-associated liver disease[J]. Annu Rev Pathol, 2023, 18 (1): 411- 438. doi: 10.1146/annurev-pathmechdis-031521-030435
4	Kwon HJ, Won YS, Park O, et al. Aldehyde dehydrogenase 2 deficiency ameliorates alcoholic fatty liver but worsens liver inflammation and fibrosis in mice[J]. Hepatology, 2014, 60 (1): 146- 157. doi: 10.1002/hep.27036
5	Zhong W, Zhang W, Li Q, et al. Pharmacological activation of aldehyde dehydrogenase 2 by Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice[J]. J Hepatol, 2015, 62 (6): 1375- 1381. doi: 10.1016/j.jhep.2014.12.022
6	Wiramon R, Yuhong L, Xin W, et al. ALDH2 deficiency increases susceptibility to binge alcohol-induced gut leakiness, endotoxemia, and acute liver injury in mice through the gut-liver axis [J]. Redox Biol, 2023, 59102577-102577.
7	Barnabei L, Laplantine E, Mbongo W, et al. NF-κB: At the borders of autoimmunity and inflammation[J]. Front Immunol, 2021, 12, 716469. doi: 10.3389/fimmu.2021.716469
8	Yalan W, Qiubing C, Shuang W, et al. Amelioration of ethanol-induced oxidative stress and alcoholic liver disease by in vivo RNAi targeting Cyp2e1[J]. Acta Pharm Sin B, 2023, 13 (9): 3906- 3918. doi: 10.1016/j.apsb.2023.01.009
9	Queck A, Bode H, Uschner FE, et al. Systemic MCP-1 levels derive mainly from injured liver and are associated with complications in cirrhosis[J]. Front Immunol, 2020, 11, 354. doi: 10.3389/fimmu.2020.00354
10	Qu L, Zhu Y, Liu Y, et al. Protective effects of ginsenoside Rk3 against chronic alcohol-induced liver injury in mice through inhibition of inflammation, oxidative stress, and apoptosis[J]. Food Chem Toxicol, 2019, 126, 277- 284. doi: 10.1016/j.fct.2019.02.032
11	陈思韵, 冯钟文, 庞丽君, 等. 基于网络药理学探究积雪草酸抗酒精性肝炎的作用机制[J]. 中国药理学通报, 2021, 37 (8): 1145- 1151. doi: 10.3969/j.issn.1001-1978.2021.08.020
12	Kumar AS, Abdeljabar AE, Nahed I. Evasion of host antioxidative response via disruption of NRF2 signaling in fatal Ehrlichia-induced liver injury[J]. PLoS Pathog, 2023, 19 (11): e1011791- e1011791. doi: 10.1371/journal.ppat.1011791
13	Sun J, Hong Z, Shao S, et al. Liver-specific Nrf2 deficiency accelerates ethanol-induced lethality and hepatic injury in vivo[J]. Toxicol Appl Pharmacol, 2021, 426, 115617. doi: 10.1016/j.taap.2021.115617
14	Jiang Y, Jiang K, Sun P, et al. Oroxylin A ameliorates non-alcoholic fatty liver disease by modulating oxidative stress and ferroptosis through the Nrf2 pathway[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2025, 1870 (5): 159628. doi: 10.1016/j.bbalip.2025.159628
15	Xiumei Y, Yulong Z, Ying P, et al. The water extract of Radix scutellariae, its total flavonoids and baicalin inhibited CYP7A1 expression, improved bile acid, and glycolipid metabolism in T2DM mice[J]. J Ethnopharmacol, 2022, 293, 115238- 115238. doi: 10.1016/j.jep.2022.115238
16	Du J, Xiang X, Xu D, et al. FXR, a key regulator of lipid metabolism, is inhibited by ER stress-mediated activation of JNK and p38 MAPK in large yellow croakers (Larimichthys crocea) fed high fat diets[J]. Nutrients, 2021, 13 (12): 4343. doi: 10.3390/nu13124343
17	Qiu YY, Zhang J, Zeng FY, et al. Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)[J]. Pharmacol Res, 2023, 192, 106786. doi: 10.1016/j.phrs.2023.106786
18	张丹, 马岚青. 过氧化物酶体增殖激活受体α在肝脏疾病中的作用及机制[J]. 临床肝胆病杂志, 2019, 35 (10): 2351- 2354.
19	王安婧, 王亚亚, 梁轩, 等. 基于PPAR治疗胆汁淤积性肝病的机制与药物研究进展[J]. 中国临床药理学与治疗学, 2023, 28 (7): 796- 808. doi: 10.12092/j.issn.1009-2501.2023.07.011
20	Anke L, Matthijs R, Joppe N, et al. Haploid genetic screens identify SPRING/ C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism[J]. Nat Commun, 2020, 11 (1): 1128. doi: 10.1038/s41467-020-14811-1
21	Chen H, Shen F, Sherban A, et al. DEPTOR suppresses lipogenesis and ameliorates hepatic steatosis and acute-on-chronic liver injury in alcoholic liver disease[J]. Hepatology, 2018, 68 (2): 496.
22	Nguyen TTP, Kim DY, Lee YG, et al. SREBP-1c impairs ULK1 sulfhydration-mediated autophagic flux to promote hepatic steatosis in high-fat-diet-fed mice [J]. Mol Cell, 2021, 81(18): 3820-3832. e7.
23	Fang C, Pan J, Qu N, et al. The AMPK pathway in fatty liver disease[J]. Front Physiol, 2022, 13, 970292. doi: 10.3389/fphys.2022.970292
24	苏蓓蓓, 杨丽霞, 梁永林, 等. 大黄糖络丸通过AMPK/mTOR/ULK1通路调控糖尿病肾病小鼠足细胞自噬的作用机制研究[J]. 中国临床药理学与治疗学, 2024, 29 (3): 260- 269. doi: 10.12092/j.issn.1009-2501.2024.03.003
25	Garbutt JC, Kampov-Polevoy AB, Pedersen C, et al. Efficacy and tolerability of baclofen in a U. S. community population with alcohol use disorder: a dose-response, randomized, controlled trial[J]. Neuropsycho Pharmacol, 2021, 46 (13): 2250- 2256. doi: 10.1038/s41386-021-01055-w
26	Lei Y, Tang L, Chen Q, et al. Disulfiram ameliorates nonalcoholic steatohepatitis by modulating the gut microbiota and bile acid metabolism[J]. Nat Commun, 2022, 13 (1): 6862. doi: 10.1038/s41467-022-34671-1
27	Ignacio N, Javier H, Beatriz R, et al. Alcoholic liver disease among patients with wernicke encephalopathy: A multicenter observational study [J]. Drug Alcohol Depend, 2022, 230109186-109186.
28	Jianzhong S, Xin Z, Jiaqiang B, et al. A polysaccharide from Alhagi honey protects the intestinal barrier and regulates the Nrf2/HO-1-TLR4/MAPK signaling pathway to treat alcoholic liver disease in mice[J]. J Ethnopharmacol, 2024, 321, 117552. doi: 10.1016/j.jep.2023.117552
29	Chen JY, Yang YJ, Meng XY, et al. Oxysophoridine inhibits oxidative stress and inflammation in hepatic fibrosis via regulating Nrf2 and NF-κB pathways[J]. Phytomedicine, 2024, 132, 155585- 155585. doi: 10.1016/j.phymed.2024.155585
30	Li Z, Fang X, Hu X, et al. Amelioration of alcohol-induced acute liver injury in C57BL/6 mice by a mixture of TCM phytochemicals and probiotics with antioxidative and anti-inflammatory effects [J]. Front Nutr, 2023, 101144589-1144589.
31	Wang M, Zhang F, Zhou J, et al. Glabridin ameliorates alcohol-caused liver damage by reducing oxidative stress and inflammation via p38 MAPK/Nrf2/NF-κB pathway[J]. Nutrients, 2023, 15 (9): 2157. doi: 10.3390/nu15092157
32	Zou J, Yang R, Feng R, et al. Ginsenoside Rk2, a dehydroprotopanaxadiol saponin, alleviates alcoholic liver disease via regulating NLRP3 and NLRP6 inflammasome signaling pathways in mice[J]. J Pharm Anal, 2023, 13 (9): 999- 1012. doi: 10.1016/j.jpha.2023.05.005
33	Pan Z, Guo J, Tang K, et al. Ginsenoside Rc modulates SIRT6-NRF2 interaction to alleviate alcoholic liver disease[J]. J Agric Food Chem, 2022, 70 (44): 14220- 14234. doi: 10.1021/acs.jafc.2c06146
34	Lai Y, Tan Q, Xv S, et al. Ginsenoside Rb1 alleviates alcohol-induced liver injury by inhibiting steatosis, oxidative stress, and inflammation[J]. Front Pharmacol, 2021, 12, 616409. doi: 10.3389/fphar.2021.616409
35	Li S, Wang N, Tan HY, et al. Modulation of gut microbiota mediates berberine-induced expansion of immuno-suppressive cells to against alcoholic liver disease[J]. Clin Transl Med, 2020, 10 (4): e112. doi: 10.1002/ctm2.112
36	Hu Y, Wang S, Wu L, et al. Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8[J]. Chin J Nat Med, 2023, 21 (9): 670- 681. doi: 10.1016/s1875-5364(23)60399-1
37	Meng T, Xiao D, Muhammed A, et al. Anti-inflammatory action and mechanisms of resveratrol[J]. Molecules, 2021, 26 (1): 229. doi: 10.3390/molecules26010229
38	Xia N, Ding Z, Dong M, et al. Protective effects of lycium ruthenicum murray against acute alcoholic liver disease in mice via the Nrf2/HO-1/NF-κB signaling pathway[J]. Pharmaceuticals (Basel), 2024, 17 (4): 497. doi: 10.3390/ph17040497
39	杨君, 胡中杰, 朱跃科, 等. 糖皮质激素与己酮可可碱治疗重症酒精性肝病效果的Meta分析[J]. 临床肝胆病杂志, 2019, 35 (7): 1546- 1550. doi: 10.3969/j.issn.1001-5256.2019.07.025
40	Nowak AJ, Relja B. The impact of acute or chronic alcohol intake on the NF-κB signaling pathway in alcohol-related liver disease[J]. Int J Mol Sci, 2020, 21 (24): 9407. doi: 10.3390/ijms21249407
41	White BA, Ramos GP, Kane S. The impact of alcohol in inflammatory bowel diseases[J]. Inflamm Bowel Dis, 2022, 28 (3): 466- 473. doi: 10.1093/ibd/izab089
42	Watanabe M, Sugawara A, Noguchi Y, et al. Jietacins, azoxy natural products, as novel NF-κB inhibitors: Discovery, synthesis, biological activity, and mode of action[J]. Eur J Med Chem, 2019, 178, 636- 647. doi: 10.1016/j.ejmech.2019.05.079
43	Xiao R, Fang J, Huang Q, et al. The effect and mechanism of Germacrone in ameliorating alcoholic fatty liver by inhibiting Nrf2/Rbp4[J]. Chin Med, 2025, 20 (1): 77. doi: 10.1186/s13020-025-01132-y
44	Ueberschlag SL, Seay JR, Roberts AH, et al. Correction: The effect of protandim® supplementation on athletic performance and oxidative blood markers in runners[J]. PLoS One, 2020, 15 (10): e0241520. doi: 10.1371/journal.pone.0241520
45	Ishida K, Kaji K, Sato S, et al. Sulforaphane ameliorates ethanol plus carbon tetrachloride-induced liver fibrosis in mice through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway[J]. J Nutr Biochem, 2021, 89, 108573. doi: 10.1016/j.jnutbio.2020.108573
46	Zhou X, Wang J, Zhou S. Poria cocos polysaccharides improve alcoholic liver disease by interfering with ferroptosis through NRF2 regulation[J]. Aging (Albany NY), 2024, 16 (7): 6147- 6162. doi: 10.18632/aging.205693
47	Guo W, Tian W, Lin L, et al. Liraglutide or insulin glargine treatments improves hepatic fat in obese patients with type 2 diabetes and nonalcoholic fatty liver disease in twenty-six weeks: A randomized placebo-controlled trial[J]. Diabetes Res Clin Pract, 2020, 170, 108487. doi: 10.1016/j.diabres.2020.108487
48	Ahmed S, Ullah N, Parveen S, et al. Effect of silymarin as an adjunct therapy in combination with sofosbuvir and ribavirin in hepatitis C patients: A miniature clinical trial[J]. Oxid Med Cell Longev, 2022, 2022, 9199190. doi: 10.1155/2022/9199190
49	Xiang X, Yang X, Shen M, et al. Ursodeoxycholic acid at 18-22 mg/kg/d showed a promising capacity for treating refractory primary biliary cholangitis[J]. Can J Gastroenterol Hepatol, 2021, 2021, 6691425. doi: 10.1155/2021/6691425
50	Sorribas M, Jakob OM, Yilmaz B, et al. FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis[J]. J Hepatol, 2019, 71 (6): 1126- 1140. doi: 10.1016/j.jhep.2019.06.017
51	Capozza T, Burkey J, Van De Wetering J, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of INT-787, a novel farnesoid X receptor agonist, in healthy volunteers: A phase 1 trial[J]. Clin Transl Sci, 2025, 18 (5): e70229. doi: 10.1111/cts.70229
52	Wu W, Zhu B, Peng X, et al. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease[J]. Biochem Biophys Res Commun, 2014, 443 (1): 68- 73. doi: 10.1016/j.bbrc.2013.11.057
53	Haga S, Yimin, Ozaki M. Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver, especially with steatosis[J]. BMC Gastroenterol, 2017, 17 (1): 9. doi: 10.1186/s12876-016-0568-3
54	Morrison A, Elgendy B. Tailoring FXR modulators for intestinal specificity: Recent progress and insights[J]. Molecules, 2024, 29 (9): 2022. doi: 10.3390/molecules29092022
55	Marzano M, Fosso B, Colliva C, et al. Farnesoid X receptor activation by the novel agonist TC-100 (3α, 7α, 11β-Trihydroxy-6α-ethyl-5β-cholan-24-oic Acid) preserves the intestinal barrier integrity and promotes intestinal microbial reshaping in a mouse model of obstructed bile acid flow[J]. Biomed Pharmacother, 2022, 153, 113380. doi: 10.1016/j.biopha.2022.113380
56	Kim YD, Lee KM, Hwang SL, et al. Inhibition of cereblon by fenofibrate ameliorates alcoholic liver disease by enhancing AMPK[J]. Biochim Biophys Acta, 2015, 1852 (12): 2662- 2670. doi: 10.1016/j.bbadis.2015.09.014
57	Chen X, Xu Y, Denning KL, et al. PPARα agonist WY-14 643 enhances ethanol metabolism in mice: Role of catalase[J]. Free Radic Biol Med, 2021, 169, 283- 293. doi: 10.1016/j.freeradbiomed.2021.04.018
58	Koizumi A, Kaji K, Nishimura N, et al. Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease[J]. World J Gastroenterol, 2024, 30 (28): 3428- 3446. doi: 10.3748/wjg.v30.i28.3428
59	Kamisuki S, Mao Q, Abu-Elheiga L, et al. A small molecule that blocks fat synthesis by inhibiting the activation of SREBP[J]. Chem Biol, 2009, 16 (8): 882- 892. doi: 10.1016/j.chembiol.2009.07.007
60	Meng H, Shen M, Li J, et al. Novel SREBP1 inhibitor cinobufotalin suppresses proliferation of hepatocellular carcinoma by targeting lipogenesis[J]. Eur J Pharmacol, 2021, 906, 174280. doi: 10.1016/j.ejphar.2021.174280
61	Kawagoe F, Mototani S, Mendoza A, et al. Structure-activity relationship studies on vitamin D-based selective SREBP/SCAP inhibitor KK-052[J]. RSC Med Chem, 2023, 14 (10): 2030- 2034. doi: 10.1039/D3MD00352C
62	Gao C, Fang L, Zhang H, et al. Metformin induces autophagy via the AMPK-mTOR signaling pathway in human hepatocellular carcinoma cells[J]. Cancer Manag Res, 2020, 12, 5803- 5811. doi: 10.2147/CMAR.S257966
63	Zhang EB, Zhang X, Wang K, et al. Antifungal agent terbinafine restrains tumor growth in preclinical models of hepatocellular carcinoma via AMPK-mTOR axis[J]. Oncogene, 2021, 40 (34): 5302- 5313. doi: 10.1038/s41388-021-01934-y
64	Hsu JY, Lin HH, Hsu CC, et al. Aqueous extract of pepino (Solanum muriactum Ait) leaves ameliorate lipid accumulation and oxidative stress in alcoholic fatty liver disease[J]. Nutrients, 2018, 10 (7): 931. doi: 10.3390/nu10070931
65	Wan W, Wei R, Xu B, et al. Qiwei Jinggan Ling regulates oxidative stress and lipid metabolism in alcoholic liver disease by activating AMPK[J]. Phytomedicine, 2024, 135, 156125. doi: 10.1016/j.phymed.2024.156125
66	Wang Y, Fan Z, Yang M, et al. Protective effects of E Se tea extracts against alcoholic fatty liver disease induced by high fat/alcohol diet: In vivo biological evaluation and molecular docking study[J]. Phytomedicine, 2022, 101, 154113. doi: 10.1016/j.phymed.2022.154113
67	Arab JP, Sehrawat TS, Simonetto DA, et al. An open-label, dose-escalation study to assess the safety and efficacy of IL-22 agonist F-652 in patients with alcohol-associated hepatitis[J]. Hepatology, 2019, 72 (2): 441- 453.
68	Saitis A, Gatselis N, Zachou K, et al. Use of TNFα antagonists in refractory AIH: revealing the unforeseen[J]. J Hepatol, 2013, 59 (1): 197- 198. doi: 10.1016/j.jhep.2013.02.029
69	Eom JA, Jeong JJ, Han SH, et al. Gut-microbiota prompt activation of natural killer cell on alcoholic liver disease[J]. Gut Microbes, 2023, 15 (2): 2281014. doi: 10.1080/19490976.2023.2281014
70	Apurva P, Shvetank S, Vikas K, et al. Fecal microbiota transplantation compared with prednisolone in severe alcoholic hepatitis patients: a randomized trial[J]. Hepatol Int, 2023, 17 (1): 249- 261. doi: 10.1007/s12072-022-10438-0
71	Mads I, Stæhr BM, Nikolaj T, et al. Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (GALA-RIF): a randomised, double-blind, placebo-controlled, phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2023, 8 (6): 523- 532. doi: 10.1016/S2468-1253(23)00010-9

Active compounds	Plants	Mechanism	Ref.
Honey polysaccharides	Honey	Activate Nrf2/HO-1 signaling pathway to eliminate hepatic oxidative stress, repair the intestinal barrier, and inhibit the LPS/TLR4/MAPK signaling pathway to alleviate hepatic inflammation.	[28]
Silymarin	Silybum marianum	Reduce the expression of key inflammatory factors, such as NF-κB, IL-6, and so forth.	[29]
Curcumin	Turmeric	Enhance the antioxidant defense ability of the liver by activating the Nrf2 signaling pathway, and intervene in the inflammatory cascade reaction by targeting and regulating cyclooxygenase-2 and inducible nitric oxide synthase.	[30]
Glabridin	Liquorice root	Alleviates ALD via p38 MAPK/Nrf2/NF-κB pathway.	[31]
Ginsenoside Rk2	Notoginseng	Reduces hepatic steatosis and hepatic oxidative stress, inhibits hepatitis, and restores damaged intestinal barriers.	[32]
Ginsenoside Rc	American ginseng	Reduces hepatocellular injury and oxidative stress in ALD, and regulates oxidative stress, inflammation, and lipid accumulation.	[33]
Ginsenoside Rb1	Cynanchum	Alleviates hepatic steatosis, reduces lipid accumulation, and alleviates inflammatory damage in ALD.	[34]
Berberine	Coptis Root	Increases the abundance of Terrisporobacter and Helicobacter and decreases the abundance of Pseudoflavonifractor, Alistipes, Ruminiclostridium, and Lachnoclostridium.	[35]
Pueraria	Kudzu root	Inhibits hepatic lipid accumulation and inflammatory response.	[36]
Resveratrol	Grape	Regulates key nuclear transcription factors such as Nrf2 and NF-κB, reduces the expression of genes such as heme oxygenase-1 and inducible nitric oxide synthase, and improves free radical scavenging activity in the human body.	[37]
Anthocyanins	Black Fruit Lycium barbarum	Activates Nrf2/HO-1, inhibits the NF-κB pathway, and reduces inflammatory response.	[38]

Active compounds	Plants	Mechanism	Ref.
Honey polysaccharides	Honey	Activate Nrf2/HO-1 signaling pathway to eliminate hepatic oxidative stress, repair the intestinal barrier, and inhibit the LPS/TLR4/MAPK signaling pathway to alleviate hepatic inflammation.	[28]
Silymarin	Silybum marianum	Reduce the expression of key inflammatory factors, such as NF-κB, IL-6, and so forth.	[29]
Curcumin	Turmeric	Enhance the antioxidant defense ability of the liver by activating the Nrf2 signaling pathway, and intervene in the inflammatory cascade reaction by targeting and regulating cyclooxygenase-2 and inducible nitric oxide synthase.	[30]
Glabridin	Liquorice root	Alleviates ALD via p38 MAPK/Nrf2/NF-κB pathway.	[31]
Ginsenoside Rk2	Notoginseng	Reduces hepatic steatosis and hepatic oxidative stress, inhibits hepatitis, and restores damaged intestinal barriers.	[32]
Ginsenoside Rc	American ginseng	Reduces hepatocellular injury and oxidative stress in ALD, and regulates oxidative stress, inflammation, and lipid accumulation.	[33]
Ginsenoside Rb1	Cynanchum	Alleviates hepatic steatosis, reduces lipid accumulation, and alleviates inflammatory damage in ALD.	[34]
Berberine	Coptis Root	Increases the abundance of Terrisporobacter and Helicobacter and decreases the abundance of Pseudoflavonifractor, Alistipes, Ruminiclostridium, and Lachnoclostridium.	[35]
Pueraria	Kudzu root	Inhibits hepatic lipid accumulation and inflammatory response.	[36]
Resveratrol	Grape	Regulates key nuclear transcription factors such as Nrf2 and NF-κB, reduces the expression of genes such as heme oxygenase-1 and inducible nitric oxide synthase, and improves free radical scavenging activity in the human body.	[37]
Anthocyanins	Black Fruit Lycium barbarum	Activates Nrf2/HO-1, inhibits the NF-κB pathway, and reduces inflammatory response.	[38]

Drug name	Mechanism of action	Development stage	Ref.
Obeticholic Acid	Activates FXR, reduces portal bacterial translocation, improves intestinal inflammation, inhibits hepatic de novo lipogenesis	Clinical usePrimary Biliary Cholangitis, Phase II trial for ALD terminated	[50]
INT-787	Activates FXR, reduces hepatic enzymes (ALT/AST), optimizes bile acid circulation, shows better efficacy than obeticholic acid	Phase II clinical trial	[51]
WAY-362450	Activates FXR, inhibits Cyp2e1, Cyp7a1, Cyp8b1, reduces triglycerides and hepatic enzymes, alleviates oxidative stress and inflammation	Preclinical animal research	[52]
GW4064	Activates FXR, inhibits CYP7A1 activity, increases FGF15 expression, reduces bile acid synthesis, decreases hepatic enzymes	Preclinical animal research	[53]
Fexaramine	Intestinally specific FXR activation, regulates downstream target genes without activating hepatic fatty acid synthesis-related genes	Preclinical research	[54]
TC-100	Activates intestinal FXR, induces Fgf15 expression to inhibit hepatic Cyp7a1, regulates entero-hepatic bile acid metabolism	Preclinical research	[55]

Drug name	Mechanism of action	Development stage	Ref.
Obeticholic Acid	Activates FXR, reduces portal bacterial translocation, improves intestinal inflammation, inhibits hepatic de novo lipogenesis	Clinical usePrimary Biliary Cholangitis, Phase II trial for ALD terminated	[50]
INT-787	Activates FXR, reduces hepatic enzymes (ALT/AST), optimizes bile acid circulation, shows better efficacy than obeticholic acid	Phase II clinical trial	[51]
WAY-362450	Activates FXR, inhibits Cyp2e1, Cyp7a1, Cyp8b1, reduces triglycerides and hepatic enzymes, alleviates oxidative stress and inflammation	Preclinical animal research	[52]
GW4064	Activates FXR, inhibits CYP7A1 activity, increases FGF15 expression, reduces bile acid synthesis, decreases hepatic enzymes	Preclinical animal research	[53]
Fexaramine	Intestinally specific FXR activation, regulates downstream target genes without activating hepatic fatty acid synthesis-related genes	Preclinical research	[54]
TC-100	Activates intestinal FXR, induces Fgf15 expression to inhibit hepatic Cyp7a1, regulates entero-hepatic bile acid metabolism	Preclinical research	[55]

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