Codonopis bulleynana Forest ex Diels (cbFeD) effectively attenuates hepatic fibrosis in CCl4-induced fibrotic mice model

Abstract Background: BALB/c mice showed easily induced Th2-type responses in several infection models. Certain macrophage phenotypes contribute to liver fibrosis. We characterized changes in macrophages phenotype (M1/M2) during fibrogenesis in liver fibrosis mice model. Methods: Carbon-tetrachloride (CCl 4 ) hepatic-fibrosis was induced in BALB/c mice. Liver macrophages isolated were identified for M1 and M2 by CD80/iNOS and CD273 (programmed death ligand 2 (PDL2)/CD206, respectively. IL-4 were induced i.p along week-2 to week-4 of CCl 4 . Liver proteins were assessed for aSMA expressions, histology and ALT levels. Results: CCl 4 -induced hepatic-fibrosis showed increased CD273 (from 20.1%± 3.1in naïve mice to 27.8%±3.2 in fibrotic mice; P=0.01) while gradual decrease in CD80 (from 12%±6.2 in naïve mice to 1.97%±0.4 in fibrotic mice; P<0.02). The overall data showed decreased M1/M2 ratio. M2-macrophages showed inhibited expressions of IFN-g, IL-12 and vitamin-D-receptor (VDR) while high TGF-b levels. ALT, H&E staining intensities and aSMA showed gradually increased along fibrosis while metabolic markers of serum insulin, vitamin D and VDR decreased. IL-4 inductions while inhibited fibrosis it elevated metabolic markers. Conclusions: M2-macrophages express less IFN-g and IL-12, which might indicate inability differentiation of naive T cells into Th1 cells. IL-4 has an anti-fibrotic effects through antagonize M2-macrophages of TGF-b and ameliorating insulin, vitamin D, VDR and consequently attenuated liver-fibrosis.

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Effectiveness of Losartan-Loaded Hyaluronic Acid (HA) Micelles for the Reduction of Advanced Hepatic Fibrosis in C3H/HeN Mice Model

PLoS ONE ◽

10.1371/journal.pone.0145512 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0145512 ◽

Cited By ~ 21

Author(s):

Reju George Thomas ◽

Myeong Ju Moon ◽

Jo Heon Kim ◽

Jae Hyuk Lee ◽

Yong Yeon Jeong

Keyword(s):

Hyaluronic Acid ◽

Hepatic Fibrosis ◽

Mice Model

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Hydrogen-rich water protects liver injury in nonalcoholic steatohepatitis though HO-1 enhancement via IL-10 and Sirt 1 signaling

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00158.2020 ◽

2021 ◽

Author(s):

Shao-Wei Li ◽

Terumi Takahara ◽

Weitao Que ◽

Masayuki Fujino ◽

Wen-zhi Guo ◽

...

Keyword(s):

Amino Acid ◽

Fatty Liver ◽

Hepatic Fibrosis ◽

Nonalcoholic Steatohepatitis ◽

Molecular Hydrogen ◽

Liver Lipid ◽

Effective Control ◽

Mice Model ◽

High Concentration ◽

Alcoholic Fatty Liver

Nonalcoholic steatohepatitis (NASH) could progress to hepatic fibrosis when absence of effective control. The purpose of our experiment was to investigate the protective effect of drinking water with high concentration of hydrogen in our study named hydrogen rich water (HRW) on mice with non-alcoholic fatty liver disease to elucidate the mechanism underlying the molecular hydrogen therapeutic action. The choline-supplemented, L-amino acid-defined (CSAA) or choline-deficient, L-amino acid-defined (CDAA) diet for 20 weeks were used to induce NASH and fibrosis in the mice model and simultaneously treated with HRW for different periods of time. Primary hepatocytes were stimulated by palmitate in order to mimic a liver lipid metabolism during fatty liver formation. Mice in the CSAA + HRW group had lower serum levels of ALT and AST and milder histological damage. The inflammatory cytokines were expressed at lower levels in the HRW group than in the CSAA group. Importantly, HRW reversed hepatocyte apoptosis as well as hepatic inflammation and fibrosis in pre-existing hepatic fibrosis specimens. Molecular hydrogen inhibits the lipopolysaccharide-induced production of inflammation cytokines through an HO-1/IL-10-independent pathway. Furthermore, HRW improved hepatic steatosis in the CSAA + HRW group. Sirt1 induction by molecular hydrogen via the HO-1/AMPK/PPARα/PPARγ pathway suppresses palmitate-mediated abnormal fat metabolism. Orally administered HRW suppressed steatosis induced by CSAA and attenuated fibrosis induced by CDAA, possibly by reducing oxidative stress and the inflammation response.

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Healing gone wrong: convergence of hemostatic pathways and liver fibrosis?

Clinical Science ◽

10.1042/cs20191102 ◽

2020 ◽

Vol 134 (16) ◽

pp. 2189-2201

Author(s):

Jessica P.E. Davis ◽

Stephen H. Caldwell

Keyword(s):

Wound Healing ◽

Liver Disease ◽

Hepatic Fibrosis ◽

Cell Activation ◽

Stellate Cell ◽

Factor Xa ◽

Clinical Trial Data ◽

Chronic Liver ◽

Healing Response ◽

Wound Healing Response

Abstract Fibrosis results from a disordered wound healing response within the liver with activated hepatic stellate cells laying down dense, collagen-rich extracellular matrix that eventually restricts liver hepatic synthetic function and causes increased sinusoidal resistance. The end result of progressive fibrosis, cirrhosis, is associated with significant morbidity and mortality as well as tremendous economic burden. Fibrosis can be conceptualized as an aberrant wound healing response analogous to a chronic ankle sprain that is driven by chronic liver injury commonly over decades. Two unique aspects of hepatic fibrosis – the chronic nature of insult required and the liver’s unique ability to regenerate – give an opportunity for pharmacologic intervention to stop or slow the pace of fibrosis in patients early in the course of their liver disease. Two potential biologic mechanisms link together hemostasis and fibrosis: focal parenchymal extinction and direct stellate cell activation by thrombin and Factor Xa. Available translational research further supports the role of thrombosis in fibrosis. In this review, we will summarize what is known about the convergence of hemostatic changes and hepatic fibrosis in chronic liver disease and present current preclinical and clinical data exploring the relationship between the two. We will also present clinical trial data that underscores the potential use of anticoagulant therapy as an antifibrotic factor in liver disease.

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