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Ginsenoside Rd Inhibited Ferroptosis to Alleviate CCl4-Induced Acute Liver Injury in Mice via cGAS/STING Pathway.

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Title: Ginsenoside Rd Inhibited Ferroptosis to Alleviate CCl4-Induced Acute Liver Injury in Mice via cGAS/STING Pathway.
Authors: Li, Yuangeng (AUTHOR), Yu, Ping (AUTHOR), Fu, Wenwen (AUTHOR), Wang, Shuo (AUTHOR), Zhao, Wenjun (AUTHOR), Ma, Yue (AUTHOR), Wu, Yi (AUTHOR), Cui, Heming (AUTHOR), Yu, Xiaofeng (AUTHOR), Fu, Li (AUTHOR), Xu, Huali (AUTHOR), Sui, Dayun (AUTHOR)
Source: American Journal of Chinese Medicine. 2023, Vol. 51 Issue 1, p91-105. 15p.
Subjects: Iron analysis, Biological models, Glutathione, Iron in the body, Acute diseases, Data analysis, Research funding, Blood collection, Phytochemicals, Oxidative stress, Descriptive statistics, Liver diseases, cGAS-STING signaling pathway, Mice, Lipid peroxidation (Biology), Immunohistochemistry, Cell death, Animal experimentation, One-way analysis of variance, Statistics, Western immunoblotting, Ginseng, Collection & preservation of biological specimens, Liver, Glutathione peroxidase, Data analysis software, Stains & staining (Microscopy), Biological assay, Biomarkers, Liver failure
Abstract: Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd is considered an active ingredient of ginseng. Evidence suggests that ginsenoside Rd may improve ischaemic stroke, nerve damage, cancer and other diseases involving apoptosis, inflammation, oxidative stress, mitochondrial injury and autophagy. However, the effects of ginsenoside Rd on CCl4-induced ALI and its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a CCl4-induced ALI model. In the Rd treatment group, Rd (10, 20 mg/kg) doses were injected intraperitoneally 1 h before and 23 h after CCl4 administration. Ferroptosis inducer imidazole ketone erastin (IKE) was injected intraperitoneally 4 h before CCl4 administration to explore the mechanism. The blood and liver were collected 24 h after CCl4 administration to investigate the effect and mechanism of ginsenoside Rd on CCl4-induced ALI. Our results showed that ginsenoside Rd inhibited CCl4-induced ALI in mice. Ginsenoside Rd also downregulated CCl4-induced serum and liver iron, 4-hydroxynonenal, and 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione and glutathione peroxidase 4 levels. In addition, ginsenoside Rd downregulated the expression of cGAS and STING. Subsequently, the ferroptosis inducer imidazole ketone erastin significantly reversed the hepatoprotective effect and influence of ginsenoside Rd with regard to the indicators mentioned above. Our study confirmed that ginsenoside Rd ameliorated CCl4-induced ALI in mice, which was related to the reduction of ferroptosis. Simultaneously, the ginsenoside Rd-mediated inhibition of the cGAS/STING pathway contributed to its antiferroptosis effect. In conclusion, our results suggested that ginsenoside Rd inhibited ferroptosis via the cGAS/STING pathway, thereby protecting mice from CCl4-induced ALI. These results suggested ginsenoside Rd may be used as a potential intervention treatment against CCl4-induced ALI. [ABSTRACT FROM AUTHOR]
Copyright of American Journal of Chinese Medicine is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
  Group: Ti
  Data: Ginsenoside Rd Inhibited Ferroptosis to Alleviate CCl<subscript>4</subscript>-Induced Acute Liver Injury in Mice via cGAS/STING Pathway.
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  Data: <searchLink fieldCode="AR" term="%22Li%2C+Yuangeng%22">Li, Yuangeng</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yu%2C+Ping%22">Yu, Ping</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fu%2C+Wenwen%22">Fu, Wenwen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Shuo%22">Wang, Shuo</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhao%2C+Wenjun%22">Zhao, Wenjun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ma%2C+Yue%22">Ma, Yue</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wu%2C+Yi%22">Wu, Yi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cui%2C+Heming%22">Cui, Heming</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yu%2C+Xiaofeng%22">Yu, Xiaofeng</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fu%2C+Li%22">Fu, Li</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xu%2C+Huali%22">Xu, Huali</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sui%2C+Dayun%22">Sui, Dayun</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22American+Journal+of+Chinese+Medicine%22">American Journal of Chinese Medicine</searchLink>. 2023, Vol. 51 Issue 1, p91-105. 15p.
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  Data: <searchLink fieldCode="DE" term="%22Iron+analysis%22">Iron analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+models%22">Biological models</searchLink><br /><searchLink fieldCode="DE" term="%22Glutathione%22">Glutathione</searchLink><br /><searchLink fieldCode="DE" term="%22Iron+in+the+body%22">Iron in the body</searchLink><br /><searchLink fieldCode="DE" term="%22Acute+diseases%22">Acute diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Data+analysis%22">Data analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Research+funding%22">Research funding</searchLink><br /><searchLink fieldCode="DE" term="%22Blood+collection%22">Blood collection</searchLink><br /><searchLink fieldCode="DE" term="%22Phytochemicals%22">Phytochemicals</searchLink><br /><searchLink fieldCode="DE" term="%22Oxidative+stress%22">Oxidative stress</searchLink><br /><searchLink fieldCode="DE" term="%22Descriptive+statistics%22">Descriptive statistics</searchLink><br /><searchLink fieldCode="DE" term="%22Liver+diseases%22">Liver diseases</searchLink><br /><searchLink fieldCode="DE" term="%22cGAS-STING+signaling+pathway%22">cGAS-STING signaling pathway</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Lipid+peroxidation+%28Biology%29%22">Lipid peroxidation (Biology)</searchLink><br /><searchLink fieldCode="DE" term="%22Immunohistochemistry%22">Immunohistochemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+death%22">Cell death</searchLink><br /><searchLink fieldCode="DE" term="%22Animal+experimentation%22">Animal experimentation</searchLink><br /><searchLink fieldCode="DE" term="%22One-way+analysis+of+variance%22">One-way analysis of variance</searchLink><br /><searchLink fieldCode="DE" term="%22Statistics%22">Statistics</searchLink><br /><searchLink fieldCode="DE" term="%22Western+immunoblotting%22">Western immunoblotting</searchLink><br /><searchLink fieldCode="DE" term="%22Ginseng%22">Ginseng</searchLink><br /><searchLink fieldCode="DE" term="%22Collection+%26+preservation+of+biological+specimens%22">Collection & preservation of biological specimens</searchLink><br /><searchLink fieldCode="DE" term="%22Liver%22">Liver</searchLink><br /><searchLink fieldCode="DE" term="%22Glutathione+peroxidase%22">Glutathione peroxidase</searchLink><br /><searchLink fieldCode="DE" term="%22Data+analysis+software%22">Data analysis software</searchLink><br /><searchLink fieldCode="DE" term="%22Stains+%26+staining+%28Microscopy%29%22">Stains & staining (Microscopy)</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+assay%22">Biological assay</searchLink><br /><searchLink fieldCode="DE" term="%22Biomarkers%22">Biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22Liver+failure%22">Liver failure</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd is considered an active ingredient of ginseng. Evidence suggests that ginsenoside Rd may improve ischaemic stroke, nerve damage, cancer and other diseases involving apoptosis, inflammation, oxidative stress, mitochondrial injury and autophagy. However, the effects of ginsenoside Rd on CCl4-induced ALI and its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a CCl4-induced ALI model. In the Rd treatment group, Rd (10, 20 mg/kg) doses were injected intraperitoneally 1 h before and 23 h after CCl4 administration. Ferroptosis inducer imidazole ketone erastin (IKE) was injected intraperitoneally 4 h before CCl4 administration to explore the mechanism. The blood and liver were collected 24 h after CCl4 administration to investigate the effect and mechanism of ginsenoside Rd on CCl4-induced ALI. Our results showed that ginsenoside Rd inhibited CCl4-induced ALI in mice. Ginsenoside Rd also downregulated CCl4-induced serum and liver iron, 4-hydroxynonenal, and 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione and glutathione peroxidase 4 levels. In addition, ginsenoside Rd downregulated the expression of cGAS and STING. Subsequently, the ferroptosis inducer imidazole ketone erastin significantly reversed the hepatoprotective effect and influence of ginsenoside Rd with regard to the indicators mentioned above. Our study confirmed that ginsenoside Rd ameliorated CCl4-induced ALI in mice, which was related to the reduction of ferroptosis. Simultaneously, the ginsenoside Rd-mediated inhibition of the cGAS/STING pathway contributed to its antiferroptosis effect. In conclusion, our results suggested that ginsenoside Rd inhibited ferroptosis via the cGAS/STING pathway, thereby protecting mice from CCl4-induced ALI. These results suggested ginsenoside Rd may be used as a potential intervention treatment against CCl4-induced ALI. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of American Journal of Chinese Medicine is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1142/S0192415X23500064
    Languages:
      – Code: eng
        Text: English
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        PageCount: 15
        StartPage: 91
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      – SubjectFull: Iron analysis
        Type: general
      – SubjectFull: Biological models
        Type: general
      – SubjectFull: Glutathione
        Type: general
      – SubjectFull: Iron in the body
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      – SubjectFull: Acute diseases
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      – SubjectFull: Data analysis
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      – SubjectFull: Research funding
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      – SubjectFull: Blood collection
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      – SubjectFull: Phytochemicals
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      – SubjectFull: Oxidative stress
        Type: general
      – SubjectFull: Descriptive statistics
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      – SubjectFull: Liver diseases
        Type: general
      – SubjectFull: cGAS-STING signaling pathway
        Type: general
      – SubjectFull: Mice
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      – SubjectFull: Lipid peroxidation (Biology)
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      – SubjectFull: Immunohistochemistry
        Type: general
      – SubjectFull: Cell death
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      – SubjectFull: Animal experimentation
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      – SubjectFull: One-way analysis of variance
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      – SubjectFull: Statistics
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      – SubjectFull: Western immunoblotting
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      – SubjectFull: Ginseng
        Type: general
      – SubjectFull: Collection & preservation of biological specimens
        Type: general
      – SubjectFull: Liver
        Type: general
      – SubjectFull: Glutathione peroxidase
        Type: general
      – SubjectFull: Data analysis software
        Type: general
      – SubjectFull: Stains & staining (Microscopy)
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      – SubjectFull: Biological assay
        Type: general
      – SubjectFull: Biomarkers
        Type: general
      – SubjectFull: Liver failure
        Type: general
    Titles:
      – TitleFull: Ginsenoside Rd Inhibited Ferroptosis to Alleviate CCl4-Induced Acute Liver Injury in Mice via cGAS/STING Pathway.
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            – D: 01
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              Text: 2023
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