Dolomiaea souliei ethyl acetate extract protected against α-naphthylisothiocyanate-induced acute intrahepatic cholestasis through regulation of farnesoid x receptor-mediated bile acid metabolism

Meng, Fan-Cheng; Zong, Wei; Wei, Xiaodong; Tao, Yun-Yi; Wang, Guowei; Liao, Zhihua; Chen, Min

doi:10.1016/j.phymed.2021.153588

Cited by 18 publications

(4 citation statements)

References 32 publications

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“…In cholestatic model group the expression of NTCP is reduced thus disturbing the enterohepatic circulation of bile acids. This decrease might be because of the injury of hepatocytes (26). In silymarin treated groups the expression of NTCP is similar to that of the control group.…”

Section: Discussionmentioning

confidence: 57%

Silymarin protects the liver from α-naphthylisothiocyanate-induced cholestasis by modulating the expression of genes involved in bile acid homeostasis

Sohail

Malkani

Tahir

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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Cholestasis is characterized by impaired bile flow which results in inflammation, cirrhosis, and ultimately liver failure. The current study is aimed to evaluate the anti-cholestatic effect of silymarin against α-naphthylisothiocyanate (ANIT) induced cholestasis. Mice were gavaged with various doses of silymarin or ursodeoxycholic acid (UDCA) for 19 days. Then they were challenged with α-naphthylisothiocyanate (ANIT) and after 48 hours the animals were sacrificed to obtain blood and liver sections. Serum levels of bilirubin, aspartate transaminase (AST), alanine transaminase (ALP), and liver histology were analyzed. mRNA expression of selected transporters (Bile salt export pump (BSEP) and sodium taurocholate cotransporting polypeptide (NTCP)) and proteins (farnesoid x receptor (FXR) and Cytochrome P450 Family 7 Subfamily A Member 1 (Cyp7a1)) involved in bile acids biosynthesis, excretion and uptake were also evaluated by quantitative PCR. The results indicated that the serum levels of bilirubin, AST, and ALP were significantly higher in a cholestatic model group as compared to an untreated control group. However, in silymarin groups, the serum level of these parameters is significantly lower than in a cholestatic model group. Liver histology also showed that silymarin prevents ANIT-induced hepatic injury. mRNA expression of FXR, BSEP, and NTCP was downregulated and expression of Cyp7a1 was upregulated in a cholestatic model group as compared to an untreated control group. However, in silymarin treatment groups, the expression of FXR, BSEP and NTCP was upregulated and the expression of Cyp7a1 was downregulated as compared to the cholestatic model group. In conclusion, silymarin could alleviate hepatic injury by modulating the expression of genes involved in bile acid homeostasis.

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Section: Discussionmentioning

confidence: 57%

Silymarin protects the liver from α-naphthylisothiocyanate-induced cholestasis by modulating the expression of genes involved in bile acid homeostasis

Sohail

Malkani

Tahir

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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“…Inflammatory cytokines and their associated signals also play a role in regulating oxidative stress, as well as fatty acid and bile acid metabolism during liver injury. 26 – 29 Indeed, hepatic lipid and bile metabolism are associated with the pathophysiology of hepatic IRI. 30 – 32 In this regard, the IAF group had higher activity in bile and fatty acid metabolism, whereas the EAD group maintained more immunomodulatory activities and showed lower metabolic activity in bile and fatty acid pathways.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling Underscores the Role of Preprocurement Allograft Metabolism and Innate Immune Status on Outcomes in Human Liver Transplantation

Kim,

Zimmermann,

Mathison

et al. 2024

Annals of Surgery Open

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Objective: The adverse effects of ischemia-reperfusion injury (IRI) remain a principal barrier to a successful outcome after lifesaving orthotopic liver transplantation (OLT). Gene expression during different phases of IRI is dynamic and modified by individual exposures, making it attractive for identifying potential therapeutic targets for improving the number of suitable organs for transplantation and patient outcomes. However, data remain limited on the functional landscape of gene expression during liver graft IRI, spanning procurement to reperfusion and recovery. Therefore, we sought to characterize transcriptomic profiles of IRI during multiple phases in human OLT. Methods: We conducted clinical data analyses, histologic evaluation, and RNA sequencing of 17 consecutive human primary OLT. We performed liver allograft biopsies at 4 time points: baseline (B, before donor cross-clamp), at the end of cold ischemia (CI), during early reperfusion (ER, after revascularization), and during late reperfusion (LR). Data were generated and then recipients grouped by post-OLT outcomes categories: immediate allograft function (IAF; n = 11) versus early allograft dysfunction (EAD; n = 6) groups. Results: We observed that CI (vs B) modified a transcriptomic landscape enriched for a metabolic and immune process. Expression levels of hallmark inflammatory response genes were higher transitioning from CI to ER and decreased from ER to LR. IAF group predominantly showed higher bile and fatty acid metabolism activity during LR compared with EAD group, while EAD group maintained more immunomodulatory activities. Throughout all time points, EAD specimens exhibited decreased metabolic activity in both bile and fatty acid pathways. Conclusions: We report transcriptomic profiles of human liver allograft IRI from prepreservation in the donor to posttransplantation in the recipient. Immunomodulatory and metabolic landscapes across ER and LR phases were different between IAF and EAD allografts. Our study also highlights marker genes for these biological processes that we plan to explore as novel therapeutic targets or surrogate markers for severe allograft injury in clinical OLT.

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“…The definite underlying mechanisms can be owing to the chain reaction of FXR-SHP and its downstream genes. The FXR-SHP axis plays a prominent part in preserving BA homeostasis by decreasing CYP7A1 to inhibit hepatic BA biosynthesis. , FXR strictly participates in the reabsorption of ileal BAs, and activated FXR can induce the synthesis of FGF15/19, which can be transferred to the liver via the portal vein. , FGF15/19 is thought to combine with FGFR4, which is highly expressed in liver tissues, repressing the expression of CYP7A1 and then limiting the synthesis of BAs . Conversely, suppression of the hepatic FXR-SHP signaling and the FGF15-FGFR4 pathway can cause liver damage.…”

Section: Discussionmentioning

confidence: 99%

Swainsonine Induces Liver Inflammation in Mice via Disturbance of Gut Microbiota and Bile Acid Metabolism

Chen

Shou

et al. 2023

J. Agric. Food Chem.

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Swainsonine induced liver inflammation in livestock; however, the underlying mechanisms, especially the role of bile acids (BAs), in the pathogenesis remained elusive. Here, our results showed that swainsonine induced hepatic inflammation via changing BA metabolism and gut microbiota in mice. Swainsonine significantly upregulated the levels of deoxycholic acid (DCA) and taurine-β-muricholic acid (T-β-MCA) in the serum and liver of mice due to the markedly increased genus Clostridium and the decreased genus Lactobacillus in the gut. As antagonists of the farnesoid X receptor (FXR), elevated DCA and T-β-MCA inhibited hepatic Fxr gene expression and thus suppressed FXR-SHP signaling and activated hepatic Cyp7a1 gene expression, which induced a significant upregulation of the total BA level in serum, contributing to liver inflammation. These findings offer new insights into the underlying mechanisms in which swainsonine induced liver inflammation in mice via the gut−liver axis and suggest that gut microbiota and its metabolite BAs may be underlying triggering factors.

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Dolomiaea souliei ethyl acetate extract protected against α-naphthylisothiocyanate-induced acute intrahepatic cholestasis through regulation of farnesoid x receptor-mediated bile acid metabolism

Cited by 18 publications

References 32 publications

Silymarin protects the liver from α-naphthylisothiocyanate-induced cholestasis by modulating the expression of genes involved in bile acid homeostasis

Silymarin protects the liver from α-naphthylisothiocyanate-induced cholestasis by modulating the expression of genes involved in bile acid homeostasis

Transcriptional Profiling Underscores the Role of Preprocurement Allograft Metabolism and Innate Immune Status on Outcomes in Human Liver Transplantation

Swainsonine Induces Liver Inflammation in Mice via Disturbance of Gut Microbiota and Bile Acid Metabolism

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