PUBLICATION
In vivo hepatoprotective activity and the underlying mechanism of chebulinic acid from Terminalia chebula fruit
- Authors
- Feng, X.H., Xu, H.Y., Wang, J.Y., Duan, S., Wang, Y.C., Ma, C.M.
- ID
- ZDB-PUB-210210-15
- Date
- 2021
- Source
- Phytomedicine : international journal of phytotherapy and phytopharmacology 83: 153479 (Journal)
- Registered Authors
- Keywords
- Chebulinic acid, Hepatoprotective activity, Nrf2, Terminalia chebula
- MeSH Terms
-
- Acetaminophen/adverse effects
- Animals
- Animals, Genetically Modified
- Chemical and Drug Induced Liver Injury/drug therapy*
- Chemical and Drug Induced Liver Injury/metabolism
- Chemical and Drug Induced Liver Injury/pathology
- Fruit/chemistry
- Gene Expression Regulation/drug effects
- Hepatocytes/drug effects
- Hydrolyzable Tannins/pharmacology*
- Larva/drug effects
- Liver/drug effects
- Liver/metabolism
- Liver/pathology
- Male
- Mice, Inbred ICR
- Plant Extracts/chemistry
- Plant Extracts/pharmacology
- Plants, Medicinal/chemistry
- Protective Agents/pharmacology*
- Terminalia/chemistry*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- tert-Butylhydroperoxide/toxicity
- PubMed
- 33561764 Full text @ Phytomedicine
Citation
Feng, X.H., Xu, H.Y., Wang, J.Y., Duan, S., Wang, Y.C., Ma, C.M. (2021) In vivo hepatoprotective activity and the underlying mechanism of chebulinic acid from Terminalia chebula fruit. Phytomedicine : international journal of phytotherapy and phytopharmacology. 83:153479.
Abstract
Background The fruit of Terminalia chebula Retz. is one of the most widely used herbal drug in Traditional medicine prescriptions including those for liver diseases. In the screening of bioactive constituents that have potential hepatoprotective activity, chebulinic acid (CA) which is a major chemical constituent of T. chebula fruit showed potent activity.
Purpose This work was conducted to investigate the hepatoprotective activity and mechanisms of CA.
Methods The hepatoprotective effect of CA was examined on hepatotoxic models of cells, zebrafish larvae and mice caused by tert-butyl hydrogen peroxide (t-BHP), acetaminophen (APAP) and CCl4, respectively.
Results Pretreatment with CA could prevent t-BHP-induced damage in L-02 hepatocytes by blocking the production of ROS, reducing LDH levels and enhancing HO-1 and NQO1 expression via MAPK/Nrf2 signaling pathway. In animal experiments, CA significantly protected mice from CCl4-induced liver injury, as demonstrated by reduced ALT, AST and MDA levels, enhanced SOD activity, improved liver histopathological changes, and the activation of the Nrf2/HO-1 signaling pathway. CA metabolized to chebulic acid isomers with DPPH radical scavenging activity. In a transgenic zebrafish line with liver specific expression of DsRed RFP, CA diminished the hepatotoxicity induced by 10 mM APAP.
Conclusion Experiments in cell and two animal models demonstrated consistent results and comprehensively expounded the hepatoprotective effects of CA.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping