Oridonin ameliorates acetaminophen‐induced acute liver injury through ATF4/PGC‐1α pathway

Yu, Dongsheng; Li, Jiye; Wang, Yu; Guo, Dongyan; Zhang, Xiaodan; Chen, Mingming; Zhou, Zhiyuan

doi:10.1002/ddr.22024

Cited by 5 publications

(2 citation statements)

References 52 publications

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“…Oridonin has been found to exert effects across multiple cellular levels [43,53,54]. Numerous investigations have associated oridonin toxicity with the modification of essential biomolecule structure and function through involvement in ROS generation [43,44,55].…”

Section: Discussionmentioning

confidence: 99%

Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/β-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity

Wu,

Gao,

Lin

et al. 2024

Toxics

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Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, β-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt/β-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells.

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Section: Discussionmentioning

confidence: 99%

Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/β-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity

Wu,

Gao,

Lin

et al. 2024

Toxics

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show abstract

“…APAP is catalyzed by cytochrome P450 2E1 (CYP2E1) to produce Nacetyl-p-benzoquinoneimine (NAPQI), which is a highly toxic product. An excessive concentration of APAP in vivo increases GSH consumption and NAPQ and ROS levels, and this process leads to ferroptosis and ERS, ultimately leading to hepatocyte death [78,79]. ERS is involved in drug-induced liver damage, and Galpha12 (Gα12) is associated with cell activity.…”

Section: Drug-induced Liver Injury (Dili)mentioning

confidence: 99%

Crosstalk between Endoplasmic Reticulum Stress and Ferroptosis in Liver Diseases

Huang,

Wang,

et al. 2024

Front. Biosci. (Landmark Ed)

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The endoplasmic reticulum (ER) played an important role in the folding, assembly and post-translational modification of proteins. ER homeostasis could be disrupted by the accumulation of misfolded proteins, elevated reactive oxygen species (ROS) levels, and abnormal Ca2+ signaling, which was referred to ER stress (ERS). Ferroptosis was a unique programmed cell death model mediated by iron-dependent phospholipid peroxidation and multiple signaling pathways. The changes of mitochondrial structure, the damage of glutathione peroxidase 4 (GPX4) and excess accumulation of iron were the main characteristics of ferroptosis. ROS produced by ferroptosis can interfere with the activity of protein-folding enzymes, leading to the accumulation of large amounts of unfolded proteins, thus causing ERS. On the contrary, the increase of ERS level could promote ferroptosis by the accumulation of iron ion and lipid peroxide, the up-regulation of ferroptosis related genes. At present, the studies on the relationship between ferroptosis and ERS were one-sided and lack of in-depth studies on the interaction mechanism. This review aimed to explore the molecular mechanism of cross-talk between ferroptosis and ERS, and provide new strategies and targets for the treatment of liver diseases.

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Inflammasome: structure, biological functions, and therapeutic targets

Dai,

Zhou,

Shi

2023

MedComm

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Inflammasomes are a group of protein complex located in cytoplasm and assemble in response to a wide variety of pathogen‐associated molecule patterns, damage‐associated molecule patterns, and cellular stress. Generally, the activation of inflammasomes will lead to maturation of proinflammatory cytokines and pyroptotic cell death, both associated with inflammatory cascade amplification. A sensor protein, an adaptor, and a procaspase protein interact through their functional domains and compose one subunit of inflammasome complex. Under physiological conditions, inflammasome functions against pathogen infection and endogenous dangers including mtROS, mtDNA, and so on, while dysregulation of its activation can lead to unwanted results. In recent years, advances have been made to clarify the mechanisms of inflammasome activation, the structural details of them and their functions (negative/positive) in multiple disease models in both animal models and human. The wide range of the stimuli makes the function of inflammasome diverse and complex. Here, we review the structure, biological functions, and therapeutic targets of inflammasomes, while highlight NLRP3, NLRC4, and AIM2 inflammasomes, which are the most well studied. In conclusion, this review focuses on the activation process, biological functions, and structure of the most well‐studied inflammasomes, summarizing and predicting approaches for disease treatment and prevention with inflammasome as a target. We aim to provide fresh insight into new solutions to the challenges in this field.

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Oridonin ameliorates acetaminophen‐induced acute liver injury through ATF4/PGC‐1α pathway

Cited by 5 publications

References 52 publications

Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/β-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity

Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/β-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity

Crosstalk between Endoplasmic Reticulum Stress and Ferroptosis in Liver Diseases

Inflammasome: structure, biological functions, and therapeutic targets

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