Thioacetamide-induced Hepatic Fibrosis Research Articles

Albiflorin ameliorates thioacetamide-induced hepatic fibrosis: The involvement of NURR1-mediated inflammatory signaling cascades in hepatic stellate cells activation

Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to the clinical pathological features of chronic human liver disease. The potential protective effect of Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against hepatic fibrosis was investigated. The mouse hepatic fibrosis model was induced with an intraperitoneal injection of TAA. Hepatic stellate cells (HSCs) were subjected to treatment with transforming growth factor-beta (TGF-β), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) was added to stimulate mouse peritoneal macrophages (MPMs), leading to the acquisition of conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels in serum or liver. The administration of ALB reduced histopathological abnormalities, and significantly regulated the expressions of nuclear receptor-related 1 protein (NURR1) and the P2X purinoceptor 7 receptor (P2×7r) in liver. ALB could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, and pro-inflammatory factor level. ALB also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, and worked as working as C-DIM12, a NURR1 agonist. Moreover, deficiency of NURR1 in activated HSCs and Kupffer cells weakened the regulatory effect of ALB on P2×7r inhibition. NURR1-mediated inhibition of inflammatory contributed to the regulation of ALB ameliorates TAA-induced hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. Therefore, ALB plays a significant part in the mitigation of TAA-induced hepatotoxicity this highlights the potential of ALB as a protective intervention for hepatic fibrosis.

Dendropanoxide Alleviates Thioacetamide-induced Hepatic Fibrosis via Inhibition of ROS Production and Inflammation in BALB/C Mice.

Hepatic fibrosis results from overproduction and excessive accumulation of extracellular matrix (ECM) proteins in hepatocytes. Although the beneficial effects of dendropanoxide (DPx) isolated from Dendropanax morbifera have been studied, its role as an anti-fibrotic agent remains elucidated. We investigated the protective effect of DPx in BALB/C mice that received thioacetamide (TAA) intraperitoneally for 6 weeks. Later DPx (20 mg/kg/day) or silymarin (50 mg/kg/day) was administered daily for 6 weeks, followed by biochemical and histological analyses of each group. Hematoxylin and eosin staining of the livers showed TAA-induced hepatic fibrosis, which was significantly reduced in the DPx group. DPx treatment significantly decreased TAA-induced hyperlipidemia as evidenced by the decreased AST, ALT, ALP, γ-GTP and serum TG concentrations and reduced the activities of catalase (CAT) and superoxide dismutase (SOD) activity. ELISA revealed reduced levels of total glutathione (GSH), malondialdehyde (MDA) and Inflammatory factors (IL-6, IL-1β, and TNF-α). Immunostaining showed reduced in collagen-1, α-SMA, and TGF-β1 expression and western blotting showed reduced levels of the apoptotic proteins, TGF-β1, p-Smad2/3, and Smad4. RT-qPCR and Western blotting revealed modifications in SIRT1, SIRT3 and SIRT4. Thus, DPx exerted a protective effect against TAA-induced hepatic fibrosis in the male BALB/C mouse model by inhibiting oxidative stress, inflammation, and apoptosis via TGF-β1/Smads signaling.

P11-20 Dendropanoxide alleviates thioacetamide-induced hepatic fibrosis by attenuation of oxidative stress and apoptosis via TGF-beta/Smad signaling pathway

P11-20 Dendropanoxide alleviates thioacetamide-induced hepatic fibrosis by attenuation of oxidative stress and apoptosis via TGF-beta/Smad signaling pathway

Mechanisms of the anti-fibrotic impact of natural nutraceuticals in thioacetamide-induced hepatic fibrosis in obese rats

Mechanisms of the anti-fibrotic impact of natural nutraceuticals in thioacetamide-induced hepatic fibrosis in obese rats

A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases

Liver fibrosis is a common chronic hepatic disease. This study was done to examine the effect of pyridoxamine against thioacetamide-induced hepatic fibrosis. Animals were divided into four groups (1) control group; (2) Thioacetamide group (200 mg/kg, i.p.) twice a week for eight weeks; (3) Pyridoxamine-treated group treated with pyridoxamine (100 mg/kg/day, i.p.) for eight weeks; (4) Thioacetamide and pyridoxamine group, in which pyridoxamine was given (100 mg/kg/day, i.p.) during thioacetamide injections. Thioacetamide treatment resulted in hepatic dysfunction manifested by increased serum levels of bilirubin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Oxidative stress was noted by increased hepatic lipid peroxidation and decreased glutathione (GSH). Increased concentrations of total nitrite/nitrate, advanced glycation end products (AGEs), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), matrix metalloproteinases (MMP-2&9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were noticed in hepatic tissues. Immunostaining sections also revealed overexpression of MMP-2, MMP-9 and collagen IV. Liver fibrosis was confirmed by severe histopathological changes. Pyridoxamine improved the assessed parameters. Moreover, histopathological and immunohistological studies supported the ability of pyridoxamine to reduce liver fibrosis. The findings of the present study provide evidence that pyridoxamine is a novel target for the treatment of liver fibrosis.

Fisetin alleviates thioacetamide-induced hepatic fibrosis in rats by inhibiting Wnt/β-catenin signaling pathway

Background Liver fibrosis is a chronic wound-healing response to liver injury of various origins and represents a major health problem. Objective The current study endeavored to investigate the repressing effect of fisetin on hepatic fibrosis induced by thioacetamide (TAA) in rats. Materials and methods Rats were injected with TAA (200 mg/kg) intraperitoneally twice per week for 6 weeks to induce liver fibrosis. Fisetin (50 and 100 mg/kg/day) or silymarin (50 mg/kg/day) were given orally on a daily basis along with TAA. Liver function parameters, oxidative stress, inflammatory and fibrogenic biomarkers as well as wnt3a, β-catenin, glycogen synthase kinase 3 (GSK-3β) and cyclin D1 were estimated. Histoapthological and immunohistochemical examinations were performed. Results Fisetin restored normal liver functions, increased reduced glutathione (GSH) level and decreased malondialdehyde (MDA), as well as inflammatory biomarkers including; tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, it lessened transforming growth factor β1 (TGF-β1), collagen I and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels as well as elevated matrix metalloproteinase-9 (MMP-9) hepatic content. Furthermore, fisetin significantly suppressed wnt3a gene expression associated with decreased β-catenin and increased GSK-3β levels. Moreover, fisetin decreased the progress of histologic hepatic fibroplasia and diminished hepatic expression of α-SMA and cyclin D1. Conclusion Fisetin curbed liver fibrosis and exhibited superior activity over silymarin through inhibition of hepatic stellate cells (HSCs) activation and proliferation via suppressing the Wnt/β-catenin pathway, modulating MMP-9 and TIMP-1, and inhibiting multiple profibrogenic factors, besides its antioxidant and anti-inflammatory effects. Therefore, fisetin is a promising therapeutic candidate for hepatic fibrosis.

Hepatoprotective Effect of Lavandula dentata leaves extracts on ThioacetamideInduced hepatic fibrosis in male albino mice

Hepatoprotective Effect of Lavandula dentata leaves extracts on ThioacetamideInduced hepatic fibrosis in male albino mice

Antifibrotic potential of carvedilol and cilostazol on liver fibrosis in rats

Objective The aim was to investigate possible prophylactic and therapeutic effects of carvedilol and cilostazol on liver fibrosis induced by thioacetamide in rats. Background Liver fibrosis is a major public health problem worldwide. Materials and methods A total of 50 adult male rats weighing 200–250 g were used and distributed in five groups (10 rats each): group I (control), group II (thioacetamide), group III (carvedilol + thioacetamide), group IV (cilostazol + thioacetamide), and group V (carvedilol + cilostazol + thioacetamide). At the end of the experiment, rats were killed, and blood samples were used for measuring serum levels of aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor-α, malondialdehyde, and glutathione peroxidase. Results Carvedilol, cilostazol, and their combination significantly decrease elevated liver enzymes alanine aminotransferase and aspartate aminotransferase by 18, 24, and 29% (P = 0.003 for all) and 25, 27, and 29% (P = 0.034 for all), respectively; decrease biomarkers of oxidative stress such as malondialdehyde and tumor necrosis factor-α by 62, 65, and 68% (P Conclusions Carvedilol and cilostazol may play a role in hepatic protection in thioacetamide-induced hepatic fibrosis. Combined treatment showed a better hepatoprotective effect than either treatment alone did.

Therapeutic efficacy of Ganoderma Lucidum on Thioacetamide-Induced Hepatic Fibrosis through Inhibition of TGF-β1 signaling in Male Rats.

The anti-fibrosis efficacy of Ganoderma lucidum (GL) was investigated on thioacetamide (TAA)-induced liver fibrosis. Experimental fibrosis was induced by (200 mg/kg TAA, i.p.) twice weekly for 6 weeks in male Sprague-Dawley rats. GL was administered to TAA rats, either as (250/500 mg/kg, i.p) daily for further 3 weeks. Repeated administration of TAA caused liver fibrosis evidenced by significant elevation of hepatic TGF-β1 accompanied by an increase in the hydroxyproline content, oxidative stress levels and liver biomarkers. Contrarily, GL treatment significantly reduced ALT, AST, total bilirubin, MDA, NO concentrations and restored SOD activity. H & E and Masson trichrome staining confirmed that GL suppressed liver fibrosis, inflammation and attenuated the histopathological alterations. GL also elicited a statistical decrease in TGF-β1 level and hydroxyproline content with a concomitant decline in NFk-B and α-SMA immunoexpression in the TAA treated rats. Furthermore, GL downregulated TNF-α and IL-1β levels in TAA-treated rats compared to the control group. Conclusion: GL possesses a pronounced protective activity against TAA-induced fibrosis in rats; It significantly inhibits oxidative stress, inflammation and diminishes fibrosis by: inhibiting NFk-B activation, reducing TGF-β mediated by PI3K-AKT pathway thus restoring the liver function, the effect was in a dose dependent manner.

Abscisic acid ameliorates oxidative stress, inflammation, and apoptosis in thioacetamide-induced hepatic fibrosis by regulating the NF-кB signaling pathway in mice

The purpose of this study was to determine whether abscisic acid (ABA) can protect against liver fibrosis induced by thioacetamide (TAA) in vivo by inhibiting apoptosis and inflammatory responses. To this end, three times per week, mice were injected intraperitoneally with TAA (200 mg/kg) for 8 weeks to induce liver fibrosis. After the fourth week of treatment, histological changes, the serum biochemical index, inflammation, and hepatocyte apoptosis factors (e.g., caspase-3, B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X [Bax]) were detected to clarify its underlying mechanism. The results clearly indicated that ABA improves TAA-induced hepatic injury and collagen accumulation in mice. Otherwise, ABA significantly reduced liver fibrosis by regulating caspase-3 and Bcl-2, α-smooth muscle actin, and collagen I. ABA inhibited the nuclear factor kappa B pathway, significantly alleviating oxidative stress and inflammatory cytokines. Therefore, ABA may be a potential therapeutic agent for preventing liver damage.

Role of cytoglobin, a novel radical scavenger, in stellate cell activation and hepatic fibrosis.

Cytoglobin (Cygb), a stellate cell-specific globin, has recently drawn attention due to its association with liver fibrosis. In the livers of both humans and rodents, Cygb is expressed only in stellate cells and can be utilized as a marker to distinguish stellate cells from hepatic fibroblast-derived myofibroblasts. Loss of Cygb accelerates liver fibrosis and cancer development in mouse models of chronic liver injury including diethylnitrosamine-induced hepatocellular carcinoma, bile duct ligation-induced cholestasis, thioacetamide-induced hepatic fibrosis, and choline-deficient L-amino acid-defined diet-induced non-alcoholic steatohepatitis. This review focuses on the history of research into the role of reactive oxygen species and nitrogen species in liver fibrosis and discusses the current perception of Cygb as a novel radical scavenger with an emphasis on its role in hepatic stellate cell activation and fibrosis.

Dunaliella salina microalgae oppose thioacetamide-induced hepatic fibrosis in rats

Several hepatic pathological conditions are correlated with the stimulation of hepatic stellate cells. This induces a cascade of events producing accretion of extracellular matrix components triggering fibrosis. Dunaliella salina, rich in carotenoids, was investigated for its potential antagonizing activity; functionally and structurally against thioacetamide (TAA) - induced hepatic fibrosis in rats. Adult male albino Wistar rats were treated with three dose levels of D. salina powder or extract (daily, p.o.); for 6 weeks, concomitantly with TAA injection. Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin and albumin were determined. Reduced glutathione (GSH), malondialdehyde (MDA), smooth muscle actin alpha (α-SMA) and collagen I hepatic contents were also estimated. Treatment with D. salina powder or extract caused a significant decline in serum levels of AST, ALT, ALP, bilirubin, MDA and hepatic contents of α-SMA and collagen I. Additionally, serum albumin and GSH hepatic content were highly elevated. Liver histopathological examination also indicated that D. salina reduced fibrosis, centrilobular necrosis, and inflammatory cell infiltration evoked by TAA. The results implied that D. salina exerts protective action against TAA-induced hepatic fibrosis in rats. The phytochemical investigation revealed high total carotenoid content prominently β-carotene (15.2 % of the algal extract) as well as unsaturated fatty acids as alpha-linolenic acid which accounts for the hepatoprotective activity.

Effect of Luteolin and Quercetin on Thioacetamide Induced Hepatic Fibrosis in Rats

Effect of Luteolin and Quercetin on Thioacetamide Induced Hepatic Fibrosis in Rats

Hepatoprotective Effect of Picroside I on Thioacetamide-Induced Hepatic Fibrosis Determined by Metabolomic and Proteomic Analyses

Background: Picroside I, a hepatoprotectant, can reduce liver injury in humans and animals. However, its anti-fibrosis effect remains unclear. This study aims to explore the mechanism of the hepatoprotective effect of picroside I on hepatic fibrosis. Methods: Male mice (12 per group) were randomly divided into six groups: control group; model group, given thioacetamide (TAA); positive group, given TAA + S-(5′-adenosyl)-L-methionine (10 mg·kg−1); low-dose group, given TAA + picroside I (25 mg·kg−1); middle-dose group, given TAA + picroside I (50 mg·kg−1); and high-dose group, given TAA + picroside I (75 mg·kg−1). Serum biochemical indicators were detected, and histological evaluation was performed. Metabolomics and proteomic analyses were conducted using liquid-chromatography coupled with tandem mass spectrometry. Findings: Picroside I can decrease the serum alanine transaminase, aspartate transaminase, collagen type IV, N-terminal peptide of type III procollagen, laminin, and hyaluronic acid levels and reduce the fibrosis area in a dose-dependent manner. In addition, picroside I altered the metabolomic profiling in hepatic fibrosis mice, including 10 urine metabolites, 16 serum metabolites, and 8 liver metabolites. Twenty-five differentially expressed proteins were reversed in the picroside I high-dose-treated group compared with the model group. Interpretation: Our results reveal whether and how picroside I protects against TAA-induced liver fibrosis in mice. Funding: National Natural Science Foundation of China, Program of Shanghai Academic/Technology Research Leader, S&T Major Special Projects, Xinglin Talent Program of Shanghai University of Traditional Chinese Medicine. Funding Statement: This work was financially supported by National Natural Science Foundation of China (project No. 81503223), the Program of Shanghai Academic/Technology Research Leader (18XD1403700; 17XD1403500), National Science and Technology (S&T) Major Special Projects (2017ZX09309006), and Xinglin Talent Program of Shanghai University of Traditional Chinese Medicine (SHUTCM2017). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The animal experiments were approved by the Institutional Animal Care and Use Committee of Shanghai University of Traditional Chinese Medicine.

Schisandra chinensis inhibiting TGFβ-induced activation of hepatic stellate cells

Hepatic fibrosis is one of the critical steps contained in the pathogenesis of liver cirrhosis. Excessive deposition of collagen contributes to the development of fibrosis in chronic liver injury. Activation of hepatic stellate cells (HSCs) plays an important role in fibrogenesis and is accountable for providing extracellular matrix components. The berry of Schisandra chinensis has been known to exert hepatoprotective properties. However, its effect on HSCs is not completely understood. Therefore, in this study, we investigated the inhibitory effect of its ethanolic extract (SBE) on hepatic fibrogenesis. We found that SBE treatment effectively reduced the serum levels of alanine aminotransferase and aspartate aminotransferase as well as collagen deposition in the hepatic parenchyma in a thioacetamide-induced hepatic fibrosis mouse model. Moreover, SBE inhibited transforming growth factor β (TGFβ)-induced mRNA expression of α-smooth muscle actin (αSMA) and collagen type 1 α1 (COL1A1) in HSCs, suggesting that SBE exerts anti-fibrotic activity by attenuating TGFβ-induced HSC activation. To identify the active components of SBE accountable for HSC inhibition, SBE was further partitioned based on the hydrophobicity of the solvents such as water, n-butanol, ethyl acetate, chloroform, and n-hexane. The n-hexane fraction was selected and further separated using analytical high-performance liquid chromatography. We found that six lignans contained in the n-hexane fraction strongly reduced TGFβ-induced expression of both αSMA and COL1A1 mRNA. These data suggest that at least six lignans contained in SBE have the strong potential to prevent TGFβ-induced HSC activation.

Study the Biochemical Activities of Anti-HCV Drugs on Thioacetamide Induced Hepatic Fibrosis

Study the Biochemical Activities of Anti-HCV Drugs on Thioacetamide Induced Hepatic Fibrosis

Use of 111In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis.

Many biochemical tests detecting the presence of liver disease are not liver-specific and may be abnormal in nonhepatic conditions. The asialoglycoprotein receptor (ASGPR) is a hepatocyte-specific receptor for Gal/GalNAc-terminated glycopeptide or glycoprotein. The number of these receptors decreases in patients with chronic liver diseases. Here, we aimed to evaluate the use of 111In-hexavalent lactoside, a known ASGPR imaging biomarker, as a more sensitive probe to detect small changes in liver reserve in animal models of chronic liver injury. Thioacetamide (TAA) treatment via intraperitoneal injection every 2 days in BALB/c mice continued for 1, 2, 3, or 4 months. The liver fibrosis stages were determined by Sirius Red staining and were based on the METAVIR classification method. Serum transaminase enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)), alkaline phosphatase, albumin, and bilirubin were measured using a FUJI FDC3500 i/s analyzer. The ASGPR staining was performed by immunohistocytochemical stain. The percentages of fibrosis and ASGPR were calculated using ImageJ software after collagen staining and anti-ASGPR staining, respectively. A nanoSPECT/CT was used for molecular imaging and liver uptake measurement. We observed fibrosis grades of F0-F1 in mice treated with TAA for 1 month, F2 in mice treated for 2 months, F3-F4 in mice treated for 3 months, and F4 in mice treated for 4 months. The levels of ALT and albumin were not significantly different in the TAA groups from those in the controls. Although the average levels of AST, alkaline phosphatase, and bilirubin in the TAA groups were different from those in the control group, there was little difference between TAA groups. More sensitive distinctions among TAA groups were detected in 111In-hexavalent lactoside uptake of ASGPR, ASGPR staining, and fibrosis % than when using the conventional AST, ALT, albumin, alkaline phosphatase, and bilirubin tests. The absorption and distribution of 111In-hexavalent lactoside were lower in the chronic hepatitis models than the normal controls. The liver reserves measured by 111In-hexavalent lactoside uptake were 71.7 ± 7.5% and 50.9 ± 5.6% after 1 and 2 months, respectively, of TAA treatment. As an ASGPR biomarker, 111In-hexavalent lactoside has higher sensitivity than traditional liver function tests and collagen stain to provide more objective data for evaluating compensated cirrhosis or changes in liver damage. ASGPR staining can reflect the regenerated hepatocytes, but the need for a biopsy limits its use. 111In-hexavalent lactoside measurement is comparable with ASGPR staining, which suggests that 111In-hexavalent lactoside measurement will be more useful as a practical, noninvasive test of chronic liver injury.

The role of oxymatrine in regulating TGF-β1 in rats with hepatic fibrosis.

To investigate whether oxymatrine (OMT) prevents hepatic fibrosis in rats by regulating liver transforming growth factor β1 (TGF-β1) level. Hepatic fibrosis was induced in rats by thioacetamide (TAA). Blood was collected at the end of week 12 to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutathione (GSH). Changes in liver tissue were observed after hematoxylin-eosin (HE) staining. Fibrosis was confirmed by Masson's collagen staining. Liver TGF-β1 level was determined by ELISA. OMT significantly reduced serum ALT and AST but increased GSH levels in rats with hepatic fibrosis. Moreover, it significantly improved liver histology in rats with TAA-induced hepatic fibrosis. It significantly decreased liver TGF-β1 level compared to that in the untreated group. It also significantly reduced collagen deposition in rats. Oxymatrine is effective in protecting rats from thioacetamide-induced hepatic fibrosis by regulating TGF-β1 expression.

Thioacetamide-induced hepatic fibrosis in the common marmoset.

The common marmoset (Callithrix jacchus) is a nonhuman primate that is used for preclinical research on stem cell transplantation therapies due to its similarity to human beings as well as its small size, enabling researchers to perform experiments without preparing a large number of cells. In this study, we developed a marmoset hepatic fibrosis model for regenerative medicine research. Six female marmosets aged 4–6 years were administered thioacetamide (TAA) at a dose of 2.5–40 mg/kg two or three times a week. Hepatic fibrosis was assessed by liver biopsy when blood chemistry indicated liver damage. Administration of TAA increased total bile acid, aspartate aminotransferase, and total bilirubin and decreased serum albumin levels. Following more than 11 weeks of continuous injection of TAA, histological analyses detected hepatic fibrosis in all animals. Type IV collagen 7S serum levels in animals with hepatic fibrosis were significantly higher than in normal animals as a possible marker of hepatic fibrosis in marmosets. Serial liver biopsies following the last administration of TAA revealed that induced fibrosis remained up to 11 weeks. The results suggest that continuous TAA administration induces persistent hepatic fibrosis in the common marmoset and this nonhuman primate hepatic fibrosis model have the possibility to evaluate the therapeutic effects of test samples to ameliorate hepatic fibrosis.

Hepatoprotection of auraptene from peels of citrus fruits against thioacetamide-induced hepatic fibrosis in mice by activating farnesoid X receptor.

Hepatic fibrosis is a pathological process that eventually leads to the development of cirrhosis and liver cancer by various types of chronic liver disease. To date, there is no standard treatment for the progression of liver fibrosis. This study aims to investigate the hepatoprotection of auraptene (AUR), a simple coumarin contained in the peels of citrus fruits such as grapefruit, against thioacetamide (TAA)-induced hepatic fibrosis in mice. The involvement of farnesoid X receptor (FXR) in the anti-fibrotic effect of AUR was further elucidated using in vivo and in vitro experiments. AUR was found to remarkably protect against liver injury induced by TAA in mice and maintain the homeostasis of bile acids via the regulation of FXR-target genes including Bsep, Mrp2, Ntcp, Cyp7a1 and Cyp8b1. Masson and Sirius red staining indicated a reduction of the collagen content in the liver of AUR treated mice. Furthermore, AUR inhibited the activation of hepatic stellate cells (HSCs) by down-regulating the expression of TGF-β1 and α-SMA and expressed anti-inflammatory effects by reducing the expression of NF-κB, TNF-α and IL-1β. However, the changes in these genes and protein as well as ameliorative liver histology induced by AUR were abrogated by FXR antagonist guggulsterone in vivo and FXR siRNA in vitro. Overall, AUR protects against TAA-induced hepatic fibrosis due to the reduction of toxic bile acids and inhibition of hepatic stellate cell (HSC) activation and inflammation, which were all in association with FXR activation. AUR might be efficacious for the prevention and treatment of hepatic fibrosis in mice.