Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via the cGAS-STING Pathway

Shen, Pan; Liang, Han; Chen, Guang; Cheng, Zhe; Liu, Qiong

doi:10.1007/s10753-021-01529-5

Cited by 24 publications

(20 citation statements)

References 75 publications

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“…Additionally, emodin ameliorates the lung injury associated with acute pancreatitis by inactivating the NLRP3/IL‐1/CXCL1 signaling 45 . Moreover, emodin protects hepatocytes from liver injury through inactivation of NLRP3 inflammasome, upregulation of Nrf2, and downregulation of the cGAS‐STING 46 . In the current study, we found that emodin decreased the protein levels of NLRP3 and ASC in OGD/R‐treated PMVECs.…”

Section: Discussionsupporting

confidence: 59%

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Emodin alleviates lung ischemia–reperfusion injury by suppressing gasdermin D‐mediated pyroptosis in rats

Jin¹,

Zhou³

et al. 2023

Clinical Respiratory J

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Background Pyroptosis refers to programmed cell death associated with inflammation. Emodin has been reported to alleviate lung injuries caused by various pathological processes and attenuate ischemia–reperfusion (I/R) injuries in diverse tissues. Methods Lewis rats were assigned into the sham, the I/R, and the I/R + emodin groups. Emodin and phosphate‐buffered saline were intraperitoneally injected into rats of the emodin group and I/R group for 30 min, respectively. These rats were then subjected to left thoracotomy followed by 90‐min clamping of the left hilum and 120‐min reperfusion. Sham‐operated rats underwent 210‐min ventilation. Lung functions, histological changes, lung edema, and cytokine levels were assessed. Protein levels were measured by western blotting. Immunofluorescence staining was conducted to evaluate pyroptosis. Results Emodin alleviated the I/R‐induced lung dysfunction, lung damages, and inflammation. Protective effects of emodin against I/R‐mediated endothelial pyroptosis was observed in vivo and in vitro. Mechanistically, emodin inactivated the TLR4/MyD88/NF‐κB/NLRP3 pathway. Conclusion Emodin attenuates lung ischemia–reperfusion injury by inhibiting GSDMD‐mediated pyroptosis in rats.

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Section: Discussionsupporting

confidence: 59%

“…45 Moreover, emodin protects hepatocytes from liver injury through inactivation of NLRP3 inflammasome, upregulation of Nrf2, and downregulation of the cGAS-STING. 46 In the current study, we found that emodin decreased the protein levels of NLRP3 and ASC in OGD/R-treated PMVECs.…”

Section: Discussionsupporting

confidence: 53%

Emodin alleviates lung ischemia–reperfusion injury by suppressing gasdermin D‐mediated pyroptosis in rats

Jin¹,

Zhou³

et al. 2023

Clinical Respiratory J

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“…Long-term or over-injection of APAP can cause hepatic sinusoidal macrophages to be activated and release a variety of pro-inflammatory cytokines, such as IL-1β and TNF-α. 21 The ELISA results demonstrated that DHM could decrease the content of IL-1β and TNF-α induced by APAP. To further verify the above experimental results, H&E, Tunel, and Hoechst 33 258 staining analysis were used to clearly and intuitively observe the liver damage caused by APAP and the protective effect of DHM pretreatment on the liver, indicating that DHM could protect liver cells from liver damage induced by APAP.…”

Section: Discussionmentioning

confidence: 95%

Evaluation on Hepatoprotection of Dihydromyricetin in Acetaminophen-Induced Hepatotoxicity Based on Analysis of Inflammation and Apoptosis Mediated by PI3K/AKT Pathway

Gong

Zhang

et al. 2022

Natural Product Communications

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Purpose: We aimed to investigate whether dihydromyricetin (DHM) could alleviate acetaminophen (APAP)-induced liver damage in mice, and to verify whether the process is associated with the PI3K/AKT signaling pathway. Methods: The contents of DHM in serum and related physiological indicators in blood and liver tissue were measured, respectively. We used haematoxylin and eosin (H&E), TUNEL, Hoechst 33,258, immunofluorescence assay and western blot methods to comprehensively assess the protective mechanism and therapeutic effect of DHM on liver damage induced by APAP (250 mg/kg) in mice. Results: APAP (250 mg/kg) could increase the expression of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β) and cause 4-hydroxy-2-nonenal (4-HNE) and Cytochrome P450 2E1 (CYP2E1) overexpression and stress response in the PI3K/AKT pathway. DHM was also detected in the serum of mice about five minutes after administration. DHM pretreatment could reverse GSH depletion and CYP2E1 overexpression, reduce the expression of ALT, AST, malondialdehyde, 4-HNE, TNF-α, and IL-1β, meanwhile it could reverse the abnormal expression of PI3K/AKT signaling pathway-related proteins which were induced by APAP. DHM pretreatment significantly reduced APAP-induced liver tissue apoptosis, necrosis, and inflammatory infiltration. Conclusion: DHM had a hepatoprotective effect on hepatotoxicity induced by APAP, which was shown by inhibiting oxidative stress and inflammatory responses, and reducing hepatocyte apoptosis by activating the PI3K/AKT signaling pathway.

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“…When APAP is combined with IFN-β, it significantly altered the transcription profile of hepatocytes, including the upregulation of genes associated with cell differentiation and the reduction of interferon-inducible genes ( Ifit-3 , Isg-15 , Oasl1 , and Zbp1 ), indicating that there may be complex interactions between APAP and IFN-β [ 238 ]. A recent study found that emodin protects the liver against AILI by inhibiting the expression of IFN-α, cyclic GMP-AMP synthase (cGAS), and its downstream signaling effector stimulator of interferon genes (STING) [ 239 ]. In conclusion, these studies suggest that a protective effect can be provided to the liver by regulating the production of interferon.…”

Section: Role Of Inflammatory Mediators In Ailimentioning

confidence: 99%

“…Kaempferol alleviates AILI by inhibiting HMGB1/TLR4/NF-κB signaling pathway and NLRP3 activation [ 263 ]. Emodin protects hepatocytes against APAP-induced injury by upregulating the nuclear factor erythroid2-related factor 2 (NRF2)-mediated antioxidant stress pathway, inhibiting NLRP3 and downregulating the cGAS-STING signaling pathway [ 239 ]. Activation of NLRP3 inflammasome is responsible for providing the second signal required for IL-1β activity in APAP hepatotoxicity.…”

Section: Role Of Inflammatory Mediators In Ailimentioning

confidence: 99%

The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity

Chen

Wang

2022

Cell Biosci

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Acute liver failure caused by drug overdose is a significant clinical problem in developed countries. Acetaminophen (APAP), a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. In addition to APAP-induced direct hepatotoxicity, the intracellular signaling mechanisms of APAP-induced liver injury (AILI) including metabolic activation, mitochondrial oxidant stress and proinflammatory response further affect progression and severity of AILI. Liver inflammation is a result of multiple interactions of cell death molecules, immune cell-derived cytokines and chemokines, as well as damaged cell-released signals which orchestrate hepatic immune cell infiltration. The immunoregulatory interplay of these inflammatory mediators and switching of immune responses during AILI lead to different fate of liver pathology. Thus, better understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression are essential to identify novel therapeutic targets for the treatment of AILI. Here, this present review aims to systematically elaborate on the underlying immunological mechanisms of AILI, its relevance to immune cells and their effector molecules, and briefly discuss great therapeutic potential based on inflammatory mediators.

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Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via the cGAS-STING Pathway

Cited by 24 publications

References 75 publications

Emodin alleviates lung ischemia–reperfusion injury by suppressing gasdermin D‐mediated pyroptosis in rats

Emodin alleviates lung ischemia–reperfusion injury by suppressing gasdermin D‐mediated pyroptosis in rats

Evaluation on Hepatoprotection of Dihydromyricetin in Acetaminophen-Induced Hepatotoxicity Based on Analysis of Inflammation and Apoptosis Mediated by PI3K/AKT Pathway

The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity

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