PMID- 37107324
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230430
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 12
IP  - 4
DP  - 2023 Apr 18
TI  - Nuciferine Effectively Protects Mice against Acetaminophen-Induced Liver Injury.
LID - 10.3390/antiox12040949 [doi]
LID - 949
AB  - Acetaminophen (APAP) overdose still poses a major clinical challenge and is a 
      leading cause of acute liver injury (ALI). N-acetylcysteine (NAC) is the only 
      approved antidote to treat APAP toxicity while NAC therapy can trigger side 
      effects including severe vomiting and even shock. Thus, new insights in 
      developing novel therapeutic drugs may pave the way for better treatment of APAP 
      poisoning. Previous research has reported that nuciferine (Nuci) possesses 
      anti-inflammatory and antioxidant properties. Therefore, the objective of this 
      study was proposed to investigate the hepatoprotective effects of Nuci and 
      explore its underlying mechanisms. Mice were intraperitoneally (i.p.) 
      administered with APAP (300 mg/kg) and subsequently injected with Nuci (25, 50, 
      and 100 mg/kg, i.p.) at 30 min after APAP overdose. Then, all mice were 
      sacrificed at 12 h after APAP challenge for further analysis. Nuci-treated mice 
      did not show any side effects and our results revealed that treating Nuci 
      significantly attenuated APAP-induced ALI, as confirmed by histopathological 
      examinations, biochemical analysis, and diminished hepatic oxidative stress and 
      inflammation. The in silico prediction and mRNA-sequencing analysis were 
      performed to explore the underlying mechanisms of Nuci. GO and KEGG enrichment of 
      the predicted target proteins of Nuci includes reactive oxygen species, drug 
      metabolism of cytochrome P450 (CYP450) enzymes, and autophagy. Furthermore, the 
      mRNA-sequencing analyses indicated that Nuci can regulate glutathione metabolic 
      processes and anti-inflammatory responses. Consistently, we found that Nuci 
      increased the hepatic glutathione restoration but decreased APAP protein adducts 
      in damaged livers. Western blot analysis further confirmed that Nuci effectively 
      promoted hepatic autophagy in APAP-treated mice. However, Nuci could not affect 
      the expression levels of the main CYP450 enzymes (CYP1A2, CYP2E1, and CYP3A11). 
      These results demonstrated that Nuci may be a potential therapeutic drug for 
      APAP-induced ALI via amelioration of the inflammatory response and oxidative 
      stress, regulation of APAP metabolism, and activation of autophagy.
FAU - Zhou, Zixiong
AU  - Zhou Z
AD  - Department of Pathology and Institute of Oncology, School of Basic Medical 
      Sciences, Fujian Medical University, Fuzhou 350122, China.
FAU - Qi, Jing
AU  - Qi J
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fujian Medical University, Fuzhou 350122, China.
FAU - Wu, Yajiao
AU  - Wu Y
AD  - Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of 
      Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
FAU - Li, Chutao
AU  - Li C
AD  - Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of 
      Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
FAU - Bao, Wenqiang
AU  - Bao W
AD  - Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of 
      Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
FAU - Lin, Xiaohuang
AU  - Lin X
AD  - Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of 
      Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
FAU - Zhu, An
AU  - Zhu A
AUID- ORCID: 0000-0002-9821-2946
AD  - Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of 
      Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
LA  - eng
GR  - 82104520/National Natural Science Foundation of China/
GR  - 82200663/National Natural Science Foundation of China/
GR  - 2021J05045/Natural Science Foundation of Fujian Province/
GR  - 2022J01199/Natural Science Foundation of Fujian Province/
PT  - Journal Article
DEP - 20230418
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC10136285
OTO - NOTNLM
OT  - acetaminophen
OT  - acute liver injury
OT  - anti-inflammatory responses
OT  - autophagy
OT  - nuciferine
OT  - oxidative stress
COIS- The authors declare no conflict of interest.
EDAT- 2023/04/28 06:42
MHDA- 2023/04/28 06:43
PMCR- 2023/04/18
CRDT- 2023/04/28 01:20
PHST- 2023/03/14 00:00 [received]
PHST- 2023/04/13 00:00 [revised]
PHST- 2023/04/14 00:00 [accepted]
PHST- 2023/04/28 06:43 [medline]
PHST- 2023/04/28 06:42 [pubmed]
PHST- 2023/04/28 01:20 [entrez]
PHST- 2023/04/18 00:00 [pmc-release]
AID - antiox12040949 [pii]
AID - antioxidants-12-00949 [pii]
AID - 10.3390/antiox12040949 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2023 Apr 18;12(4):949. doi: 10.3390/antiox12040949.