Atractylenolide Ⅰ improves acetaminophen-induced acute liver injury in mice by inhibiting MAPK/NF-κB signaling pathway.
10.19540/j.cnki.cjcmm.20211008.701
- Author:
Zhi-Mei MA
1
;
Shang-Lei LAI
1
;
Jin-Yan ZHU
2
;
Qin-Chao DING
3
;
Xiao-Bing DOU
1
;
Song-Tao LI
2
Author Information
1. School of Life Sciences, Zhejiang Chinese Medical University Hangzhou 310053, China.
2. School of Public Health, Zhejiang Chinese Medical University Hangzhou 310053, China.
3. School of Life Sciences, Zhejiang Chinese Medical University Hangzhou 310053, China College of Animal Sciences, Zhejiang University Hangzhou 310058, China.
- Publication Type:Journal Article
- Keywords:
MAPK;
NF-κB;
acetaminophen;
acute liver injury;
atractylenolide Ⅰ
- MeSH:
Acetaminophen/adverse effects*;
Animals;
Chemical and Drug Induced Liver Injury/drug therapy*;
Lactones;
Mice;
NF-kappa B/metabolism*;
Sesquiterpenes;
Signal Transduction
- From:
China Journal of Chinese Materia Medica
2022;47(4):1017-1023
- CountryChina
- Language:Chinese
-
Abstract:
This study explored the protective effect of atractylenolide Ⅰ(AO-Ⅰ) against acetaminophen(APAP)-induced acute liver injury(ALI) in mice and its underlying mechanism. C57 BL/6 J mice were randomly divided into a control group, an APAP group(500 mg·kg~(-1)), a low-dose combination group(500 mg·kg~(-1) APAP + 60 mg·kg~(-1) AO-Ⅰ), and a high-dose combination group(500 mg·kg~(-1) APAP + 120 mg·kg~(-1) AO-Ⅰ). ALI was induced by intraperitoneal injection of APAP(500 mg·kg~(-1)). AO-Ⅰ by intragastric administration was performed 2 hours before APAP treatment, and the control group received the same dose of solvent by intragastric administration or intraperitoneal injection. The protective effect of AO-Ⅰ against APAP-induced ALI was evaluated by detecting alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels in the plasma and H&E staining in liver tissues of mice. The malondialdehyde(MDA) and glutathione(GSH) content and catalase(CAT) activity in mouse liver tissues were detected to evaluate the effect of AO-Ⅰ on APAP-induced oxidative stress in the liver. The proteins in the liver p38 mitogen-activated protein kinase(p38 MAPK), c-jun N-terminal kinase(JNK), and nuclear factor kappa-B p65(NF-κB p65) signaling pathways were measured by Western blot, and the liver inflammatory cytokines interleukin-1β(IL-1β) and interleukin-6(IL-6) were detected by real-time PCR. Compared with the APAP group, the combination groups showed reduced APAP-induced ALT level and liver MDA content, potentiated liver CAT activity, and elevated GSH content. Mechanistically, AO-Ⅰ treatment significantly inhibited APAP-up-regulated MAPK phosphorylation and NF-κB p65, and significantly reduced the transcriptional activities of IL-1β and IL-6, downstream targets of NF-κB p65. AO-Ⅰ can improve APAP-induced ALI and the underlying mechanism is related to the inhibition of the MAPK/NF-κB p65 signaling pathway in APAP-challenged mice.
