Preventive and therapeutic effect of bioactive component of licorice on antidepressant-induced liver injury.
10.19540/j.cnki.cjcmm.20220608.402
- Author:
Wen-Qing MU
1
;
Guang XU
2
;
Jia ZHAO
1
;
Yuan-Yuan CHEN
1
;
Zhao-Fang BAI
3
;
Xiao-He XIAO
3
Author Information
1. School of Pharmacy, Chengdu University of Traditional Chinese Medicine Chengdu 611137, China Department of Hepatology, the Fifth Medical Center of PLA General Hospital Beijing 100039, China.
2. Department of Hepatology, the Fifth Medical Center of PLA General Hospital Beijing 100039, China School of Traditional Chinese Medicine, Capital Medical University Beijing 100069, China.
3. Department of Hepatology, the Fifth Medical Center of PLA General Hospital Beijing 100039, China.
- Publication Type:Journal Article
- Keywords:
antidepressant;
echinatin;
hepatotoxicity;
licorice;
paroxetine
- MeSH:
Animals;
Humans;
Mice;
Antidepressive Agents/adverse effects*;
Chemical and Drug Induced Liver Injury, Chronic/prevention & control*;
Glycyrrhiza/chemistry*;
Inflammasomes/drug effects*;
Interleukin-1beta/metabolism*;
Lipopolysaccharides/toxicity*;
Mice, Inbred C57BL;
NLR Family, Pyrin Domain-Containing 3 Protein;
Paroxetine/adverse effects*;
Tumor Necrosis Factor-alpha;
Chalcones/therapeutic use*
- From:
China Journal of Chinese Materia Medica
2022;47(22):6146-6154
- CountryChina
- Language:Chinese
-
Abstract:
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.
