Therapeutic potential of curcumin in non-alcoholic steatohepatitis

2005 ◽  
Vol 18 (2) ◽  
pp. 212-221 ◽  
Author(s):  
Haim Shapiro ◽  
Rafael Bruck
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Animal Studies ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Stellate Cell ◽  
Indirect Evidence ◽  
Deficient Diet ◽  
Alcoholic Steatohepatitis ◽  
Ppar Γ

Non-alcoholic steatohepatitis (NASH) may be associated with a number of clinical conditions, but it occurs most commonly in patients with insulin resistance. There is as yet no established disease-modifying treatment, and a safe and broadly available agent that targets hepatic steatosis, insulin resistance, inflammation and fibrosis is necessary. The polyphenolic compound curcumin exhibits antioxidant and anti-inflammatory properties, inhibits NF-κB and activates PPAR-γ. In rodents, curcumin prevents dietary-induced hepatic steatosis, hepatic stellate cell activation and production of fibrotic proteins, and ameliorates steatohepatitis induced by the intake of alcohol or a methionine–choline-deficient diet. Indirect evidence suggests that curcumin may improve insulin sensitivity in diabetes and inflammatory states. The present paper reviews the numerous cellular and animal studies indicating that curcumin attenuates many of the pathophysiological processes involved in the development and progression of NASH. It is suggested that basic and clinical studies on curcumin in the development and progression of NASH are indicated.

scholarly journals Progranulin attenuates liver fibrosis by downregulating the inflammatory response

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Wonbeak Yoo ◽  
Jaemin Lee ◽  
Kyung Hee Noh ◽  
Sangmin Lee ◽  
Dana Jung ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Raw 264.7 Cells ◽  
Protective Effects ◽  
Deficient Diet ◽  
A Cell

Abstract Progranulin (PGRN) is a cysteine-rich secreted protein expressed in endothelial cells, immune cells, neurons, and adipocytes. It was first identified for its growth factor-like properties, being implicated in tissue remodeling, development, inflammation, and protein homeostasis. However, these findings are controversial, and the role of PGRN in liver disease remains unknown. In the current study, we examined the effect of PGRN in two different models of chronic liver disease, methionine‐choline‐deficient diet (MCD)-induced non-alcoholic steatohepatitis (NASH) and carbon tetrachloride (CCl4)-induced liver fibrosis. To induce long-term expression of PGRN, PGRN-expressing adenovirus was delivered via injection into the tibialis anterior. In the CCl4-induced fibrosis model, PGRN showed protective effects against hepatic injury, inflammation, and fibrosis via inhibition of nuclear transcription factor kappa B (NF-κB) phosphorylation. PGRN also decreased lipid accumulation and inhibited pro-inflammatory cytokine production and fibrosis in the MCD-induced NASH model. In vitro treatment of primary macrophages and Raw 264.7 cells with conditioned media from hepatocytes pre-treated with PGRN prior to stimulation with tumor necrosis factor (TNF)-α or palmitate decreased their expression of pro-inflammatory genes. Furthermore, PGRN suppressed inflammatory and fibrotic gene expression in a cell culture model of hepatocyte injury and primary stellate cell activation. These observations increase our understanding of the role of PGRN in liver injury and suggest PGRN delivery as a potential therapeutic strategy in chronic inflammatory liver disease.

scholarly journals Prolyl oligopeptidase attenuates hepatic stellate cell activation through induction of Smad7 and PPAR-γ

2017 ◽  
Vol 13 (2) ◽  
pp. 780-786 ◽  
Author(s):  
Da Zhou ◽  
Jing Wang ◽  
Ling-Nan He ◽  
Bing-Hang Li ◽  
Yong-Nian Ding ◽  
...  
Keyword(s):  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Stellate Cell ◽  
Prolyl Oligopeptidase ◽  
Hepatic Stellate Cell Activation ◽  
Ppar Γ

scholarly journals 3D hESC exosomes enriched with miR-6766-3p ameliorates liver fibrosis by attenuating activated stellate cells through targeting the TGFβRII-SMADS pathway

2021 ◽  
Author(s):  
Ning Wang ◽  
Xiajing Li ◽  
Zhiyong Zhong ◽  
Yaqi Qiu ◽  
Shoupei Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Stellate Cell ◽  
Embryonic Stem ◽  
Luciferase Reporter ◽  
Fibrotic Liver

Abstract BackgroundExosomes secreted from stem cells exerted salutary effects on the fibrotic liver. Herein, the roles of exosomes derived from human embryonic stem cell (hESC) in anti-fibrosis were extensively investigated. Compared with two-dimensional (2D) culture, the clinical and biological relevance of three-dimensional (3D) cell spheroids were greater because of their higher regeneration potential since they behave more like cells in vivo. In our study, exosomes derived from 3D human embryonic stem cells (hESC) spheroids and the monolayer (2D) hESCs were collected and compared the therapeutic potential for fibrotic liver in vitro and in vivo. ResultsIn vitro, PKH26 labled-hESC-Exosomes were shown to be internalized and integrated into TGFβ-activated-LX2 cells, and reduced the expression of profibrogenic markers, thereby regulating cellular phenotypes. TPEF imaging indicated that PKH26-labled-3D-hESC-Exsomes possessed an enhanced capacity to accumulate in the livers and exhibited more dramatic therapeutic potential in the injured livers of fibrosis mouse model. 3D-hESC-Exosomes decreased profibrogenic markers and liver injury markers, and improved the level of liver functioning proteins, eventually restoring liver function of fibrosis mice. miRNA array revealed a significant enrichment of miR-6766-3p in 3D-hESC-Exosomes, moreover, bioinformatics and dual luciferase reporter assay identified and confirmed the TGFβRII gene as the target of miR-6766-3p. Furthermore, the delivery of miR-6766-3p into activated-LX2 cells decreased cell proliferation, chemotaxis and profibrotic effects, and further investigation demonstrated that the expression of target gene TGFβRII and its downstream SMADs proteins, especially phosphorylated protein p-SMAD2/3 was also notably down-regulated by miR-6766-3p. These findings unveiled that miR-6766-3p in 3D-hESC-Exosomes inactivated SMADs signaling by inhibiting TGFβRII expression, consequently attenuating stellate cell activation and suppressing liver fibrosis. ConclusionsOur results showed that miR-6766-3p in the 3D-hESC-Exosomes inactivates smads signaling by restraining TGFβRII expression, attenuated LX2 cell activation and suppressed liver fibrosis, suggesting that 3D-hESC-Exosome enriched-miR6766-3p is a novel anti-fibrotic therapeutics for treating chronic liver disease. These results also proposed a significant strategy that 3D-Exo could be used as natural nanoparticles to rescue liver injury via delivering antifibrotic miR-6766-3p.

Everolimus is a potent inhibitor of activated hepatic stellate cell functions in vitro and in vivo, while demonstrating anti-angiogenic activities

2014 ◽  
Vol 126 (11) ◽  
pp. 775-791 ◽  
Author(s):  
Anne-Christine Piguet ◽  
Syamantak Majumder ◽  
Uma Maheshwari ◽  
Reji Manjunathan ◽  
Uttara Saran ◽  
...  
Keyword(s):  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Potent Inhibitor ◽  
Therapeutic Potential ◽  
Stellate Cell ◽  
Fibrotic Liver ◽  
Cell Functions ◽  
Hepatocellular Carcinomas

The present study demonstrates the therapeutic potential of everolimus for the treatment of hepatocellular carcinomas in the fibrotic liver by inhibiting hepatic stellate cell activation and angiogenesis.

scholarly journals Amplified Inhibition of Stellate Cell Activation Pathways by PPAR-γ, RAR and RXR Agonists

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76541 ◽  
Author(s):  
Efrat Sharvit ◽  
Shirley Abramovitch ◽  
Shimon Reif ◽  
Rafael Bruck
Keyword(s):  
Cell Activation ◽  
Stellate Cell ◽  
Ppar Γ ◽  
Activation Pathways
Sign in / Sign up

Export Citation Format

Share Document