Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
10.19540/j.cnki.cjcmm.20250103.704
- Author:
Jing-Zhuo TIAN
1
;
Lian-Mei WANG
1
;
Yan YI
1
;
Zhong XIAN
1
;
Nuo DENG
1
;
Yong ZHAO
1
;
Chun-Ying LI
1
;
Yu-Shi ZHANG
1
;
Su-Yan LIU
1
;
Jia-Yin HAN
1
;
Chen PAN
1
;
Chen-Yue LIU
1
;
Jing MENG
1
;
Ai-Hua LIANG
2
Author Information
1. State Key Laboratory for Quality Ensurance and Sustainalbe Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700,China.
2. State Key Laboratory for Quality Ensurance and Sustainalbe Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700,China Qianhai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation,Northwest Institute of Plateau Biology, Chinese Academy of Sciences Xining 810008,China.
- Publication Type:Journal Article
- Keywords:
FXR-RXR-CYP7A1 pathway;
bile acids homeostasis;
clinical medication safety;
emodin;
hepatic damage
- MeSH:
Emodin/administration & dosage*;
Bile Acids and Salts/metabolism*;
Animals;
Male;
Liver/injuries*;
Chemical and Drug Induced Liver Injury/genetics*;
Drugs, Chinese Herbal/adverse effects*;
Humans;
Rats, Sprague-Dawley;
Mice;
Rats
- From:
China Journal of Chinese Materia Medica
2025;50(11):3079-3087
- CountryChina
- Language:Chinese
-
Abstract:
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
