Bile acid homeostasis paradigm and its connotation with cholestatic liver diseases

Yang, Tingting; Khan, Ghulam Jilany; Wu, Ziteng; Wang, Xue; Zhang, Luyong; Jiang, Zhenzhou

doi:10.1016/j.drudis.2018.09.007

Cited by 52 publications

(34 citation statements)

References 182 publications

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“…Accumulating studies have shown that oral quercetin treatment can significantly reduce plasma total cholesterol (T‐CHO) level in diabetic animal models (Eitah et al, ; Latifi, Mohammadpour, Fathi, & Nourani, ; Zhang, Dong, Wang, & Zhang, ). Being synthesized from cholesterol in the liver, bile acids (BAs) represents a major pathway for the elimination of steroids from the body (Chavez‐Talavera, Tailleux, Lefebvre, & Staels, ; T. Yang, Khan, et al, ; Yang et al, ). Besides the promotion of fat‐soluble nutrients absorption, BAs also participate in many metabolic processes, including glucose, lipids, and energy homeostasis by acting as physiological small molecule scavengers and signaling molecules.…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating studies have shown that oral quercetin treatment can significantly reduce plasma total cholesterol (T-CHO) level in diabetic animal models (Eitah et al, 2019;Latifi, Mohammadpour, Fathi, & Nourani, 2019;Zhang, Dong, Wang, & Zhang, 2016). Being synthesized from cholesterol in the liver, bile acids (BAs) represents a major pathway for the elimination of steroids from the body (Chavez-Talavera, Tailleux, Lefebvre, & Staels, 2017;T. Yang, Khan, et al, 2019;.…”

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confidence: 99%

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Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Yang

Cai

et al. 2019

Phytotherapy Research

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175

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Multiphase pathological processes involve in Type 2 diabetes (T2DM)‐induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM‐induced NAFLD were investigated. T2DM‐induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM‐induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM‐induced production of interleukin 1 beta, interleukin 6, and TNF‐α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM‐induced NAFLD. In high D‐glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM‐induced NAFLD.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Yang

Cai

et al. 2019

Phytotherapy Research

Self Cite

175

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“…In cholestatic liver disease, both biliary epithelial cells and hepatocytes are exposed in their microenvironment to toxic bile acids arising from the disruption of bile acid homeostasis [1]. Hydrophobic bile acids such as glycochenodeoxycholate (GCDC) are highly cytotoxic and can induce both hepatocyte and bile duct epithelial cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Sirt6 opposes glycochenodeoxycholate-induced apoptosis of biliary epithelial cells through the AMPK/PGC-1α pathway

Chen

et al. 2020

Cell Biosci

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Background: Induction of biliary epithelial cell apoptosis by toxic bile acids is involved in the development of cholestatic disease, but the underlying molecular mechanism is not clear. The purpose of this study was to investigate the molecular mechanisms involved in Sirt6 protection against the apoptosis of human intrahepatic biliary epithelial cells (HiBEC) induced by the bile acid glycochenodeoxycholate (GCDC). Results: Sirt6 was either overexpressed or knocked down in HiBEC, with or without GCDC pretreatment. The CCK-8 assay was used to assess cell viability and, Hoechst 33258 staining was used to determine apoptotic rate. Mitochondrial DNA (mtDNA) copy number, malondialdehyde (MDA) and reactive oxygen species (ROS) production were detected to evaluate the severity of the mitochondrial dysfunction and oxidative stress. The mRNA and protein levels of PGC-1α, Nrf1, and Nrf2 were analyzed using RT-qPCR and western blot assay. The results showed that Sirt6 opposed GCDC-induced apoptosis in HiBEC via up-regulating PGC-1α expression and stabilizing mtDNA. We used agonists and inhibitors of AMPK to demonstrate that Sirt6 increased PGC-1α expression through the AMPK pathway whereas GCDC had the opposite effect. Finally, western blot, luciferase assay, and co-immunoprecipitation were used to describe a direct interaction and acetylation modification of PGC-1α by Sirt6. Conclusion: Our data illuminated that Sirt6 ameliorated GCDC-induced HiBEC apoptosis by upregulating PGC-1α expression through the AMPK pathway and its deacetylation effect.

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“…Currently, OCA is not cost‐effective and widely available due its high price (Samur et al, ). Besides OCA, with the in‐depth research, a growing number of high‐affinity FXR agonists such as PX20606 (PX‐102), fexaramine, LMB763, tropifexor (LJN452), GS‐9674, and so on are developed at a clinical stage and waiting for wide application (Yang, Khan, et al, ). Liver transplantation remains one of the few available options for severe cholestatic patients without proper treatment (Nishio et al, ).…”

Section: Introductionmentioning

confidence: 99%

Natural products for the prevention and treatment of cholestasis: A review

Jiang

Zhang

et al. 2020

Phytotherapy Research

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Cholestasis is a common manifestation of decreased bile flow in various liver diseases. It results in fibrosis and even cirrhosis without proper treatment. It is believed that a wide range of factors, including transporter dysfunction, oxidative stress, inflammatory damage, and immune disruption, can cause cholestasis. In recent years, natural products have drawn much attention for specific multiple-target activities in diseases. Many attempts have been made to investigate the anticholestatic effects of natural products with advanced technology. This review summarizes recent studies on the biological activities and mechanisms of recognized compounds for cholestasis treatment. Natural products, including various flavonoids, phenols, acids, quinones, saponins, alkaloids, glycosides, and so on, function as comprehensive regulators via ameliorating oxidative stress, inflammation, and apoptosis, restoring bile acid balance with hepatic transporters, and adjusting immune disruption. Moreover, in this progress, nuclear factor erythroid 2-related factor 2, reactive oxygen species production, heme oxygenase-1, NF-κB, cholesterol 7 alpha-hydroxylase, and farnesoid X receptors are thought as main targets for the activity of natural products. Therefore, this review presents the detailed mechanisms that include multiple targets and diverse signalling pathways. Natural products are the valuable when seeking novel therapeutic agents to treat cholestatic liver diseases.

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Bile acid homeostasis paradigm and its connotation with cholestatic liver diseases

Cited by 52 publications

References 182 publications

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Sirt6 opposes glycochenodeoxycholate-induced apoptosis of biliary epithelial cells through the AMPK/PGC-1α pathway

Natural products for the prevention and treatment of cholestasis: A review

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