Chicoric Acid Ameliorates Nonalcoholic Fatty Liver Disease via the AMPK/Nrf2/NFκB Signaling Pathway and Restores Gut Microbiota in High-Fat-Diet-Fed Mice.

Ding X, Jian T, Li J, Lv H, Tong B, Li J, Meng X, Ren B, Chen J

Oxidative medicine and cellular longevity3 Nov 2020Cited by 95 (Europe PMC)

PMID33204402PMCIDPMC7657699DOI10.1155/2020/9734560PepBankPUB-33204402

Summary

This study examines the effects of chicoric acid (CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat-diet- (HFD-) fed C57BL/6 mice. CA treatment decreased body weight and white adipose weight, mitigated hyperglycemia and dyslipidemia, and reduced hepatic steatosis in HFD-fed mice. Moreover, CA treatment reversed HFD-induced oxidative stress and inflammation both systemically and locally in the liver, evidenced by the decreased serum malondialdehyde (MDA) abundance, increased serum superoxide dismutase (SOD) activity, lowered in situ reactive oxygen species (ROS) in the liver, decreased serum and hepatic inflammatory cytokine levels, and reduced hepatic inflammatory cell infiltration in HFD-fed mice. In addition, CA significantly reduced lipid accumulation and oxidative stress in palmitic acid- (PA-) treated HepG2 cells. In particular, we identified AMPK as an activator of Nrf2 and an inactivator of NFκB. CA upregulated AMPK phosphorylation, the nuclear protein level of Nrf2, and downregulated NFκB protein level both in HFD mice and PA-treated HepG2 cells. Notably, AMPK inhibitor compound C blocked the regulation of Nrf2 and NFκB, as well as ROS overproduction mediated by CA in PA-treated HepG2 cells, while AMPK activator AICAR mimicked the effects of CA. Similarly, Nrf2 inhibitor ML385 partly blocked the regulation of antioxidative genes and ROS overproduction by CA in PA-treated HepG2 cells. Interestingly, high-throughput pyrosequencing of 16S rRNA suggested that CA could increase Firmicutes-to-Bacteroidetes ratio and modify gut microbial composition towards a healthier microbial profile. In summary, CA plays a preventative role in the amelioration of oxidative stress and inflammation via the AMPK/Nrf2/NFκB signaling pathway and shapes gut microbiota in HFD-induced NAFLD.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Mechanism
In PA-treated HepG2 cells, AICAR mimicked the increase in nuclear Nrf2 protein level produced by chicoric acid.
In plain wordsIn cells treated with palmitic acid, AICAR mimicked chicoric acid's effect on Nrf2.
Peptide
AICAR (acadesine)
Outcome
IncreaseNuclear Nrf2 protein level
Study
humann: not reported in source
PA-treated HepG2 cells
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated
Source sentences
Summary
Notably, AMPK inhibitor compound C blocked the regulation of Nrf2 and NFκB, as well as ROS overproduction mediated by CA in PA-treated HepG2 cells, while AMPK activator AICAR mimicked the effects of CA.
2 context sentences(design, population, supporting numbers)
Summary · context
CA upregulated AMPK phosphorylation, the nuclear protein level of Nrf2, and downregulated NFκB protein level both in HFD mice and PA-treated HepG2 cells.
Summary · context
In addition, CA significantly reduced lipid accumulation and oxidative stress in palmitic acid- (PA-) treated HepG2 cells.
Show in the study text Report a problemFND-3320440201
02LabIn vitro (cells)Mechanism
In PA-treated HepG2 cells, AICAR mimicked chicoric acid's suppression of NFκB.
In plain wordsIn cells treated with palmitic acid, AICAR mimicked chicoric acid's suppression of NFκB.
Peptide
AICAR (acadesine)
Outcome
DecreaseNFκB regulation
Study
humann: not reported in source
PA-treated HepG2 cells
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated
Source sentences
Summary
Notably, AMPK inhibitor compound C blocked the regulation of Nrf2 and NFκB, as well as ROS overproduction mediated by CA in PA-treated HepG2 cells, while AMPK activator AICAR mimicked the effects of CA.
2 context sentences(design, population, supporting numbers)
Summary · context
CA upregulated AMPK phosphorylation, the nuclear protein level of Nrf2, and downregulated NFκB protein level both in HFD mice and PA-treated HepG2 cells.
Summary · context
In addition, CA significantly reduced lipid accumulation and oxidative stress in palmitic acid- (PA-) treated HepG2 cells.
Show in the study text Report a problemFND-3320440202
03LabIn vitro (cells)Mechanism
In PA-treated HepG2 cells, AICAR mimicked chicoric acid's reduction of ROS overproduction.
In plain wordsIn cells treated with palmitic acid, AICAR mimicked chicoric acid's reduction of excess reactive oxygen species.
Peptide
AICAR (acadesine)
Outcome
DecreaseROS overproduction
Study
humann: not reported in source
PA-treated HepG2 cells
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated
Source sentences
Summary
Notably, AMPK inhibitor compound C blocked the regulation of Nrf2 and NFκB, as well as ROS overproduction mediated by CA in PA-treated HepG2 cells, while AMPK activator AICAR mimicked the effects of CA.
1 context sentence(design, population, supporting numbers)
Summary · context
In addition, CA significantly reduced lipid accumulation and oxidative stress in palmitic acid- (PA-) treated HepG2 cells.
Show in the study text Report a problemFND-3320440203

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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