Corosolic acid ameliorates non-alcoholic steatohepatitis induced by high-fat diet and carbon tetrachloride by regulating TGF-β1/Smad2, NF-κB, and AMPK signaling pathways.

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Abstract

Title:: Corosolic acid ameliorates non-alcoholic steatohepatitis induced by high-fat diet and carbon tetrachloride by regulating TGF-β1/Smad2, NF-κB, and AMPK signaling pathways.
Authors:: Liu G; College of Pharmacy, Yanbian University, Jilin, China.
Cui Z; Department of Pharmacy, Yanbian University Hospital, Jilin, China.
Gao X; College of Pharmacy, Yanbian University, Jilin, China.
Liu H; College of Pharmacy, Yanbian University, Jilin, China.
Wang L; College of Integration Science, Yanbian University, Jilin, China.
Gong J; College of Pharmacy, Yanbian University, Jilin, China.
Wang A; College of Pharmacy, Yanbian University, Jilin, China.
Zhang J; College of Pharmacy, Yanbian University, Jilin, China.
Ma Q; College of Pharmacy, Yanbian University, Jilin, China.
Huang Y; Department of Gastroenterology, Yanbian University Hospital, Jilin, China.
Piao G; College of Pharmacy, Yanbian University, Jilin, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Jilin, China.
Yuan H; College of Pharmacy, Yanbian University, Jilin, China.; College of Integration Science, Yanbian University, Jilin, China.; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Jilin, China.
Source:: Phytotherapy research : PTR [Phytother Res] 2021 Sep; Vol. 35 (9), pp. 5214-5226. Date of Electronic Publication: 2021 Jul 02.
Publication Type:: Journal Article
Language:: English
Imprint Name(s):: Publication: : Chichester : Wiley
Original Publication: London : Heyden & Son, c1987-
MeSH Terms:: Non-alcoholic Fatty Liver Disease*/drug therapy
Triterpenes*/pharmacology
Signal Transduction/*drug effects
AMP-Activated Protein Kinases/metabolism ; Animals ; Carbon Tetrachloride ; Diet, High-Fat/adverse effects ; Liver/metabolism ; Liver Cirrhosis ; Mice ; NF-kappa B/metabolism ; Smad2 Protein ; Transforming Growth Factor beta1/metabolism
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Grant Information:: 81660614 National Natural Science Foundation of China; 82060674 National Natural Science Foundation of China; JJKH20210587KJ Science and Technology Planning Project of the Jilin Provincial Education Department
Contributed Indexing:: Keywords: AMPK; NF-κB; TGF-β1/Smad2; corosolic acid; liver fibrosis
Substance Nomenclature:: 0 (NF-kappa B)
0 (Smad2 Protein)
0 (Smad2 protein, mouse)
0 (Tgfb1 protein, mouse)
0 (Transforming Growth Factor beta1)
0 (Triterpenes)
AMX2I57A98 (corosolic acid)
CL2T97X0V0 (Carbon Tetrachloride)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
Entry Date(s):: Date Created: 20210702 Date Completed: 20210929 Latest Revision: 20210929
Update Code:: 20240105
DOI:: 10.1002/ptr.7195
PMID:: 34213784
: Academic Journal

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Hawthorn (Crataegus pinnatifida Bunge. var. major) is an edible and medicinal fruit that is very common in food and traditional Chinese medicine. Corosolic acid (CA), a pentacyclic triterpenoid, which is an active component of hawthorn (Crataegus pinnatifida Bunge. var. major), has been exhibiting various pharmacological activities such as antidiabetic, antibacterial, anticancer, antiinflammatory, and antioxidant effects. The study aimed to evaluate the effect of CA on non-alcoholic steatohepatitis (NASH) in mice induced by 60 kcal% high-fat diet (HFD) and carbon tetrachloride (CCl 4 ). CA lowered liver index and serum AST, ALT, TG, and TC levels compared to those in the model group. Histological analyses of the liver tissues of mice treated with CA revealed significantly decreased number of lipid droplets and alleviated inflammation and fibrosis. CA inhibited the transcripts of pro-fibrogenic markers (including α-SMA, collagen I, and TIMP-1) and the levels of pro-inflammatory cytokines (including TNF-α, IL-1β, caspase-1, and IL-6) associated with hepatic fibrosis, and NF-κB translocation and TGF-β1/Smad2 and AMPK pathways. In addition, CA reduced lipid accumulation via the regulation of AMPK and NF-κB activation in FFA-induced steatotic HepG2 cells. CA also decreased α-SMA, collagen I expressions, and Smad2 phosphorylation, which were reduced by TGF-β1 treatment in LX2 cells. Our results suggested that CA ameliorated NASH through regulating TGF-β1/Smad2, NF-κB, and AMPK signaling pathways, and CA could be developed as a potential health functional food or therapeutic agent for NASH patients.
(© 2021 John Wiley & Sons Ltd.)

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