2.Immunomodulation and liver protection of Yinchenhao decoction against concanavalin A-induced chronic liver injury in mice.
Shi-li JIANG ; Xu-dong HU ; Ping LIU
Journal of Integrative Medicine 2015;13(4):262-268
OBJECTIVEThis study investigated the immunoregulatory and protective roles of Yinchenhao decoction, a compound of Chinese herbal medicine, in a mouse model of concanavalin A (ConA)-induced chronic liver injury.
METHODSFemale BalB/c mice were randomly divided into 4 groups: normal control, ConA model, ConA model treated with Yinchenhao decoction (400 mg/kg, orally), and ConA model treated with dexamethasone (0.5 mg/kg, orally). All treatments were given once a day for 28 d. Except of the normal control, mice received tail vein injection of ConA (10 mg/kg) on days 7, 14, 21, and 28, at 1 h after treatment with Yinchenhao decoction or dexamethasone or saline to induce chronic liver injury.
RESULTSRepeated ConA injection induced chronic liver injury, which was evidenced by inflammatory cell infiltration and necrosis, increased serum alanine aminotranferease activities, decreased albumin levels, and an imbalanced expression of immunoregulatory genes in the liver tissues including significantly enhanced interferon-γ, interleukin-4, monocyte chemotactic protein-1, and cluster of differentiation 163 mRNA levels, and reduced tumor necrosis factor-α and interleukin-6 mRNA levels. Treatment with Yinchenhao decoction significantly reversed the ConA-induced changes in immunoregulatory gene expression in the liver tissues, reduced serum alanine aminotranferease activity, enhanced serum albumin level, and attenuated the extent of liver inflammation and necrosis. Furthermore, Yinchenhao decoction did not result in hepatocyte degeneration and spleen weight loss that were observed in mice received long-term treatment with dexamethasone.
CONCLUSIONYinchenhao decoction treatment protected liver against the ConA-induced chronic liver damage and improved liver function, which were associated with the modulation of gene expression related to immune/inflammatory response.
Animals ; Chemical and Drug Induced Liver Injury, Chronic ; immunology ; prevention & control ; Concanavalin A ; toxicity ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Immunomodulation ; Mice ; Mice, Inbred BALB C
3.Preventive and therapeutic effect of bioactive component of licorice on antidepressant-induced liver injury.
Wen-Qing MU ; Guang XU ; Jia ZHAO ; Yuan-Yuan CHEN ; Zhao-Fang BAI ; Xiao-He XIAO
China Journal of Chinese Materia Medica 2022;47(22):6146-6154
Since exploding rates of modern mental diseases, application of antidepressants has increased. Worryingly, the antidepressant-induced liver injury has gradually become a serious health burden. Furthermore, since most of the knowledge about antidepressant hepatotoxicity are from pharmacovigilance and clinical case reports and lack of observational studies, the underlying mechanisms are poorly understood and there is a lack of efficient treatment strategies. In this study, antidepressant paroxetine directly triggered inflammasome activation evidenced by caspase-1 activation and downstream effector cytokines interleukin(IL)-1β secretion. The pretreatment of echinatin, a bioactive component of licorice, completely blocked the activation. This study also found that echinatin effectively inhibited the production of inflammasome-independent tumor necrosis factor α(TNF)-α induced by paroxetine. Mechanistically, the accumulation of mitochondrial reactive oxygen species(mtROS) was a key upstream event of paroxetine-induced inflammasome activation, which was dramatically inhibited by echinatin. In the lipopolysaccharide(LPS)-mediated idiosyncratic drug-induced liver injury(IDILI) model, the combination of LPS and paroxetine triggered aberrant activation of the inflammasome to induce idiosyncratic hepatotoxicity, which was reversed by echinatin pretreatment. Notably, this study also found that various bioactive components of licorice had an inhibitory effect on paroxetine-triggered inflammasome activation. Meanwhile, multiple antidepressant-induced aberrant activation of the inflammasome could be completely blocked by echinatin pretreatment. In conclusion, this study provides a novel insight for mechanism of antidepressant-induced liver injury and a new strategy for the treatment of antidepressant-induced hepatotoxicity.
Animals
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Humans
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Mice
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Antidepressive Agents/adverse effects*
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Chemical and Drug Induced Liver Injury, Chronic/prevention & control*
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Glycyrrhiza/chemistry*
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Inflammasomes/drug effects*
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Interleukin-1beta/metabolism*
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Lipopolysaccharides/toxicity*
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Mice, Inbred C57BL
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NLR Family, Pyrin Domain-Containing 3 Protein
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Paroxetine/adverse effects*
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Tumor Necrosis Factor-alpha
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Chalcones/therapeutic use*