Theaflavine inhibits hepatic stellate cell activation by modulating the PKA/LKB1/AMPK/GSK3β cascade and subsequently enhancing Nrf2 signaling

Gao, Shu; Sun, Haiguo; Zhang, Tiantian; Zhu, Aibin; Liu, Xiao; Wang, C; Song, Anning; Deng, Xukun

doi:10.1016/j.ejphar.2023.175964

Cited by 7 publications

(6 citation statements)

References 88 publications

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“…Similarly, many bioactive chemicals ameliorate LF via suppressing HSC activation. 19,26,[31][32][33] Phenomena above suggest that restraining HSC activation is a feasible strategy for combating LF. Based on previously published literatures, the concentration of EGT applied in cultured cells is around 10 μM, 34 while the dosage of EGT used in mice via gavage is around 15 mg kg −1 .…”

Section: Discussionmentioning

confidence: 99%

“…LX-2 HSCs were cultured as described previously. 19 The possible cytotoxic effects of EGT on LX-2 HSCs were detected by using the CCK8 cell viability assay kit. Cell transfection was performed by using Lipo8000™ following the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Molecular docking was performed as described previously. 19 Briefly, the 3D structures of the human Foxa3 protein (PDB ID: 1VTN) and the chemical structure of EGT (PubChem CID: 5351619) were downloaded from the PDB and PubChem databases, respectively. Molecular docking was carried out using PyMOL and AutoDockTools.…”

Section: Molecular Dockingmentioning

confidence: 99%

“…These HSCs become spontaneously activated after being cul-tured in vitro for about 1 week, characterized by increased expression of molecular markers of HSC activation. 19,29,30 To assess the inhibitory effects of EGT on their spontaneous activation, we treated primary HSCs with EGT 2 days after their isolation, and this treatment lasted for 4 days. At this time, primary HSCs treated with the vehicle finished their spontaneous activation, allowing us to clearly assess whether EGT suppressed the spontaneous activation of primary HSCs.…”

Section: Egt Modulates Anti-lf Signaling In Mouse Primary Hscsmentioning

confidence: 99%

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Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Shu,

Lei,

et al. 2023

Food Funct.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Molecular Dockingmentioning

confidence: 99%

Section: Egt Modulates Anti-lf Signaling In Mouse Primary Hscsmentioning

confidence: 99%

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Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Shu,

Lei,

et al. 2023

Food Funct.

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“…Mouse AML-12 hepatocytes were cultured and transfected as described previously [72]. Sequences of siRNA targeting mouse LKB1 (si-LKB1) and the corresponding control siRNA (si-Con) were the same as described previously [73].…”

Section: Cells and Transfectionmentioning

confidence: 99%

Ethanol Extract of Rosa rugosa Ameliorates Acetaminophen-Induced Liver Injury via Upregulating Sirt1 and Subsequent Potentiation of LKB1/AMPK/Nrf2 Cascade in Hepatocytes

Lei,

Zhu

et al. 2023

Molecules

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Acetaminophen (APAP)-induced liver injury is a common hepatic disease resulting from drug abuse. Few targeted treatments are available clinically nowadays. The flower bud of Rosa rugosa has a wide range of biological activities. However, it is unclear whether it alleviates liver injury caused by APAP. Here, we prepared an ethanol extract of Rosa rugosa (ERS) and analyzed its chemical profile. Furthermore, we revealed that ERS significantly ameliorated APAP-induced apoptosis and ferroptosis in AML-12 hepatocytes and dampened APAP-mediated cytotoxicity. In AML-12 cells, ERS elevated Sirt1 expression, boosted the LKB1/AMPK/Nrf2 axis, and thereby crippled APAP-induced intracellular oxidative stress. Both EX527 and NAM, which are chemically unrelated inhibitors of Sirt1, blocked ERS-induced activation of LKB1/AMPK/Nrf2 signaling. The protection of ERS against APAP-triggered toxicity in AML-12 cells was subsequently abolished. As expression of LKB1 was knocked down, ERS still upregulated Sirt1 but failed to activate AMPK/Nrf2 cascade or suppress cytotoxicity provoked by APAP. Results of in vivo experiments showed that ERS attenuated APAP-caused hepatocyte apoptosis and ferroptosis and improved liver injury and inflammation. Consistently, ERS boosted Sirt1 expression, increased phosphorylations of LKB1 and AMPK, and promoted Nrf2 nuclear translocation in the livers of APAP-intoxicated mice. Hepatic transcriptions of HO-1 and GCLC, which are downstream antioxidant genes of Nrf2, were also significantly increased in response to ERS. Our results collectively indicated that ERS effectively attenuates APAP-induced liver injury by activating LKB1/AMPK/Nrf2 cascade. Upregulated expression of Sirt1 plays a crucial role in ERS-mediated activation of LKB1.

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Comparative studies on the antioxidant, anticancer and anti-inflammatory activities of green tea, orthodox black tea and CTC black tea

Deo,

Devi,

Sijisha

et al. 2023

J Food Sci Technol

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Theaflavine inhibits hepatic stellate cell activation by modulating the PKA/LKB1/AMPK/GSK3β cascade and subsequently enhancing Nrf2 signaling

Cited by 7 publications

References 88 publications

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Ethanol Extract of Rosa rugosa Ameliorates Acetaminophen-Induced Liver Injury via Upregulating Sirt1 and Subsequent Potentiation of LKB1/AMPK/Nrf2 Cascade in Hepatocytes

Comparative studies on the antioxidant, anticancer and anti-inflammatory activities of green tea, orthodox black tea and CTC black tea

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Theaflavine inhibits hepatic stellate cell activation by modulating the PKA/LKB1/AMPK/GSK3β cascade and subsequently enhancing Nrf2 signaling

Cited by 7 publications

References 88 publications

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl4-induced liver fibrosis in mice

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl4-induced liver fibrosis in mice

Ethanol Extract of Rosa rugosa Ameliorates Acetaminophen-Induced Liver Injury via Upregulating Sirt1 and Subsequent Potentiation of LKB1/AMPK/Nrf2 Cascade in Hepatocytes

Comparative studies on the antioxidant, anticancer and anti-inflammatory activities of green tea, orthodox black tea and CTC black tea

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Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice