Pinocembrin from Penthorum chinense Pursh suppresses hepatic stellate cells activation through a unified SIRT3-TGF-β-Smad signaling pathway

Zhou, Fayang; Wang, Anqi; Li, Dan; Wang, Ying; Lin, Ligen

doi:10.1016/j.taap.2018.01.009

Cited by 35 publications

(25 citation statements)

References 68 publications

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“…Consistently, Sirt3 -overexpressing transgenic mice have attenuated liver fibrosis associated with reduced SMAD3 protein levels in liver tissues, therefore SIRT3 plays a role in regulating TGFβ signaling [ 109 ]. According to this, four pathways for SIRT3 antifibrotic function have been proposed [ 110 ]. It is known that reactive oxygen species (ROS) induce HSCs transdifferentiation and stimulate ECM production [ 111 ].…”

Section: Acetylation/deacetylation Of Histones In Liver Fibrosismentioning

confidence: 99%

“…It is known that reactive oxygen species (ROS) induce HSCs transdifferentiation and stimulate ECM production [ 111 ]. In line with this, SIRT3 potentiates superoxide dismutase 2 (SOD2) activity via its deacetylation, which prevents the accumulation of ROS in LX2 and HSC-T6 cells [ 110 ]. In addition, SIRT3 also reduces intracellular oxidative stress in LX2 cells through inhibition of NOX (NADPH oxidase) activity, family of enzymes responsible for the generation of superoxide and hydrogen peroxide [ 112 ].…”

Section: Acetylation/deacetylation Of Histones In Liver Fibrosismentioning

confidence: 99%

“…SIRT3 interferes in the TGFβ pathway in HSCs through the degradation of SMAD proteins via activation of GSK-3β (Glycogen synthase kinase 3 beta). SIRT3-mediated GSK-3β activation induces β-catenin phosphorylation and degradation, which is crucial to prevent HSCs transdifferentiation [ 63 , 110 ] and, in part mediates the antifibrogenic effects of the activation of AMPK signalling. Indeed, siRNA-mediated AMPK silencing suppresses SIRT3 expression [ 108 ].…”

Section: Acetylation/deacetylation Of Histones In Liver Fibrosismentioning

confidence: 99%

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Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target?

Clavería-Cabello

Colyn

Arechederra

et al. 2020

Cells

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Chronic liver diseases (CLD) represent a worldwide health problem. While CLDs may have diverse etiologies, a common pathogenic denominator is the presence of liver fibrosis. Cirrhosis, the end-stage of CLD, is characterized by extensive fibrosis and is markedly associated with the development of hepatocellular carcinoma. The most important event in hepatic fibrogenesis is the activation of hepatic stellate cells (HSC) following liver injury. Activated HSCs acquire a myofibroblast-like phenotype becoming proliferative, fibrogenic, and contractile cells. While transient activation of HSCs is part of the physiological mechanisms of tissue repair, protracted activation of a wound healing reaction leads to organ fibrosis. The phenotypic changes of activated HSCs involve epigenetic mechanisms mediated by non-coding RNAs (ncRNA) as well as by changes in DNA methylation and histone modifications. During CLD these epigenetic mechanisms become deregulated, with alterations in the expression and activity of epigenetic modulators. Here we provide an overview of the epigenetic alterations involved in fibrogenic HSCs transdifferentiation with particular focus on histones acetylation changes. We also discuss recent studies supporting the promising therapeutic potential of histone deacetylase inhibitors in liver fibrosis.

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Section: Acetylation/deacetylation Of Histones In Liver Fibrosismentioning

confidence: 99%

Section: Acetylation/deacetylation Of Histones In Liver Fibrosismentioning

confidence: 99%

Section: Acetylation/deacetylation Of Histones In Liver Fibrosismentioning

confidence: 99%

See 1 more Smart Citation

Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target?

Clavería-Cabello

Colyn

Arechederra

et al. 2020

Cells

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“…The water extract of P. chinense (5.15 and 10.30 g/kg body weight/day for 4 wk) protects the liver against chronic ethanol-induced injury in mice by attenuating ROS generation and MDA level, restoring GSH depletion, and increasing SOD and GPx activities with silymarin (86 mg/kg body weight) as a positive control [61]. In a recent study, pinocembrin from P. chinense suppresses the activation of both human HSC LX-2 and rat HSC-T6 cells at the concentrations of 10, 20, and 40 µM, mediating through ROS production alleviation, TGF-β1 inhibition, and prevention of Smad nuclear translocation, which suggest its potential for protection against liver fibrosis [62]. Further in vivo studies are needed to verify the anti-fibrotic effect of P. chinense and pinocembrin.…”

Section: Flavonoidsmentioning

confidence: 97%

Fighting Liver Fibrosis with Naturally Occurring Antioxidants

et al. 2018

Self Cite

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Liver fibrosis is a wound-healing response characterized by the accumulation of extracellular matrix following various liver injuries, which results in the deformation of the normal liver architecture and the development of liver cirrhosis and even hepatocellular carcinoma. Numerous in vitro and in vivo studies indicated that oxidative stress mediates the initiation and progression of liver fibrosis. Overaccumulation of reactive oxygen species disrupts macromolecules, induces necrosis and apoptosis of hepatocytes, stimulates the production of pro-fibrogenic mediators, and directly activates hepatic stellate cells, thereby resulting in liver damage and initiating liver fibrosis. Ameliorating oxidative stress is a potential therapeutic strategy for the treatment of liver fibrosis. Natural antioxidants have attracted increasing attention in treating liver fibrosis due to their safety and efficacy. In this review, the pathogenesis of liver fibrosis and the role of oxidative stress in liver fibrosis were discussed. Naturally occurring antioxidants that can treat and prevent liver fibrosis were summarized. Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of oxidative stress in liver fibrosis to representative antioxidants for treating liver fibrosis. Naturally occurring antioxidants show a potential for further investigations as lead compounds in fighting liver fibrosis.

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“…Aqueous extracts of PCP [ 35 ] had a protective effect against ethanol-induced acute and chronic liver injury and in an ethanol-induced chronic liver injury model. Aqueous extract of PCP downregulated MDA levels in alcohol fatty liver rats by inhibiting CYP2E1-mediated oxidative stress.…”

Section: The Therapeutic Effects Of Pcp On Alcohol Fatty Liver Dismentioning

confidence: 99%

An Overview of the Mechanism of Penthorum chinense Pursh on Alcoholic Fatty Liver

Zhao

Liao

Zhou

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Alcohol liver disease (ALD) caused by excessive alcohol consumption is a progressive disease, and alcohol fatty liver disease is the primary stage. Currently, there is no approved drug for its treatment. Abstinence is the best way to heal, but patients’ compliance is poor. Unlike other chronic diseases, alcohol fatty liver disease is not caused by nutritional deficiencies; it is caused by the molecular action of ingested alcohol and its metabolites. More and more studies have shown the potential of Penthorum chinense Pursh (PCP) in the clinical use of alcohol fatty liver treatment. The purpose of this paper is to reveal from the essence of PCP treatment of alcohol liver mechanism mainly by the ethanol dehydrogenase (ADH) and microsomal ethanol oxidation system-dependent cytochrome P4502E1 (CYP2E1) to exert antilipogenesis, antioxidant, anti-inflammatory, antiapoptotic, and autophagy effects, with special emphasis on its mechanisms related to SIRT1/AMPK, KEAP-1/Nrf2, and TLR4/NF-κB. Overall, data from the literature shows that PCP appears to be a promising hepatoprotective traditional Chinese medicine (TCM).

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Pinocembrin from Penthorum chinense Pursh suppresses hepatic stellate cells activation through a unified SIRT3-TGF-β-Smad signaling pathway

Cited by 35 publications

References 68 publications

Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target?

Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target?

Fighting Liver Fibrosis with Naturally Occurring Antioxidants

An Overview of the Mechanism of Penthorum chinense Pursh on Alcoholic Fatty Liver

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