IκB kinase-beta inhibitor attenuates hepatic fibrosis in mice

Wei, Jue; Shi, Min; Wu, Weiqi; Xu, Hui; Wang, Ting; Wang, Na; Ma, Jun; Wang, Yugang

doi:10.3748/wjg.v17.i47.5203

Cited by 12 publications

(13 citation statements)

References 48 publications

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“…Based on a previous study showing that 100 mg/kg amlexanox was no side effect to experimental mouse, 22 different doses of amlexanox (25,50, and 100 mg/kg) were used in our in vivo experiments. To induce hepatotoxin-mediated liver fibrosis, CCl 4 (Sigma-Aldrich; CCl 4 , 2:5 v/v in corn oil) or same volume of corn oil (Sigma-Aldrich) were administered intraperitoneally (i.p.)…”

Section: Murine Fibrosis Induction and Amlexanox Treatmentmentioning

confidence: 99%

“…25 However, the roles of TBK1 and IKKε in the pathogenesis of liver fibrosis are still unknown. 25 However, the roles of TBK1 and IKKε in the pathogenesis of liver fibrosis are still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…23,24 These findings led us to predict that modulation of TBK1 and showing that inhibition of canonical IKKβ significantly attenuates hepatic inflammation and fibrogenesis in mice with non-alcoholic fatty liver disease by reducing NF-κB activation. 25 However, the roles of TBK1 and IKKε in the pathogenesis of liver fibrosis are still unknown. Therefore, we aimed to clarify the precise role of non-canonical IKKs in the development and resolution of liver fibrosis by using amlexanox.…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, these mice were orally administered with vehicle or amlexanox(25,50, and 100 mg/kg) daily. Mice were i.p.…”

mentioning

confidence: 99%

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Dual TBK1/IKKɛ inhibitor amlexanox attenuates the severity of hepatotoxin‐induced liver fibrosis and biliary fibrosis in mice

Zhou

Zhao

et al. 2019

J Cellular Molecular Medi

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Although numerous studies have suggested that canonical IκB kinases (IKK) play a key role in the progression of liver fibrosis, the role of non-canonical IKKε and TANKbinding kinase 1 (TBK1) on the development and progression of liver fibrosis remains unclear. To demonstrate such issue, repeated injection of CCl 4 was used to induce hepatotoxin-mediated chronic liver injury and biliary fibrosis was induced by 0.1% diethoxycarbonyl-1, 4-dihydrocollidine diet feeding for 4 weeks. Mice were orally administered with amlexanox (25, 50, and 100 mg/kg) during experimental period.Significantly increased levels of TBK1 and IKKε were observed in fibrotic livers or hepatic stellate cells (HSCs) isolated from fibrotic livers. Interestingly, amlexanox treatment significantly inhibited the phosphorylation of TBK1 and IKKε accompanied by reduced liver injury as confirmed by histopathologic analysis, decreased serum biochemical levels and fibro-inflammatory responses. Additionally, treatment of amlexanox promoted the fibrosis resolution. In accordance with these findings, amlexanox treatment suppressed HSC activation and its related fibrogenic responses by partially inhibiting signal transducer and activator of transcription 3. Furthermore, amlexanox decreased the activation and inflammatory responses in Kupffer cells. Collectively, we found that inhibition of the TBK1 and IKKε by amlexanox is a promising therapeutic strategy to cure liver fibrosis.

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Section: Murine Fibrosis Induction and Amlexanox Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, these mice were orally administered with vehicle or amlexanox(25,50, and 100 mg/kg) daily. Mice were i.p.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Dual TBK1/IKKɛ inhibitor amlexanox attenuates the severity of hepatotoxin‐induced liver fibrosis and biliary fibrosis in mice

Zhou

Zhao

et al. 2019

J Cellular Molecular Medi

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“…To evaluate liver inflammation, a liver biopsy assessment system was employed to evaluate the inflammation score in our experiments. 22 As our present study showed, Cy-3-G could decrease neutrophils and attained a lower liver inflammation score (Figure 1; Table 2). Furthermore, it reduced liver CD45 positive cells, which were leukocytes, infiltrated to the periportal zone as inflammation cells ( Figure 5).…”

Section: ■ Discussionmentioning

confidence: 61%

Cyanidin-3-O-β-glucoside Purified from Black Rice Protects Mice against Hepatic Fibrosis Induced by Carbon Tetrachloride via Inhibiting Hepatic Stellate Cell Activation

Jiang

Guo

Shen

et al. 2015

J. Agric. Food Chem.

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This study investigated whether cyanidin-3-O-β-glucoside (Cy-3-G), a predominant anthocyanin, could exert a protective role on liver injury and its further mechanisms of the anti-fibrosis actions in mice. The results demonstrated that the treatment of Cy-3-G (800 mg/kg diet) for 8 weeks significantly attenuated hepatotoxicity and fibrosis in carbon tetrachloride (CCl4) administered mice. Cy-3-G strongly down-regulated the expression of α-smooth muscle actin (α-SMA), desmin, and matrix metalloproteinase (MMPs), which showed its suppression effect on the activation of hepatic stellate cells (HSCs). In addition, Cy-3-G favorably regulated oxidative stress and apoptosis in liver. Furthermore, Cy-3-G ameliorated the infiltration of inflammatory cells such as neutrophils and leukocytes and meanwhile suppressed the production of pro-inflammatory cytokines and growth factors. In conclusion, daily intake of Cy-3-G could prevent liver fibrosis progression in mice induced by CCl4 through inhibiting HSC activation, which provides a basis for clinical practice of liver fibrosis prevention.

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If steatosis is the atherosclerosis of the liver, are statins the “aspirin” for steatosis?

Lonardo

Loria

2012

Digestive and Liver Disease

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IκB kinase-beta inhibitor attenuates hepatic fibrosis in mice

Abstract: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a remedial target for liver fibrosis.

Cited by 12 publications

References 48 publications

Dual TBK1/IKKɛ inhibitor amlexanox attenuates the severity of hepatotoxin‐induced liver fibrosis and biliary fibrosis in mice

Dual TBK1/IKKɛ inhibitor amlexanox attenuates the severity of hepatotoxin‐induced liver fibrosis and biliary fibrosis in mice

Cyanidin-3-O-β-glucoside Purified from Black Rice Protects Mice against Hepatic Fibrosis Induced by Carbon Tetrachloride via Inhibiting Hepatic Stellate Cell Activation

If steatosis is the atherosclerosis of the liver, are statins the “aspirin” for steatosis?

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