Hepatotoxicity and Anti-osteoporotic Mechanism of Evodiamine
10.13422/j.cnki.syfjx.20241315
- VernacularTitle:基于斑马鱼模型的吴茱萸碱肝损伤及抗骨质疏松症作用机制
- Author:
Jiaqi LI
1
;
Xiaolu CHEN
1
;
Xiaoyu TAO
1
;
Shan LU
1
;
Qiqi FAN
1
;
Jiarui WU
1
;
Chongjun ZHAO
1
Author Information
1. Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medical/Traditional Chinese Medicine（TCM） Processing Technology Inheritance Base of National Administration of TCM， School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 102488， China
- Publication Type:Journal Article
- Keywords:
evodiamine;
zebrafish;
hepatotoxicity;
osteoporosis;
mechanism
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(4):79-86
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveBased on the zebrafish model， the hepatotoxicity and anti-osteoporotic activity of evodiamine （EVO） were studied. The mechanism of EVO in treating osteoporosis was explored by using network pharmacology and real-time polymerase chain reaction（Real-time PCR）. MethodsThree days after fertilization （3 dpf）， zebrafish were randomly selected and exposed to different concentrations of EVO solution for 96 hours. The mortality rate of zebrafish at different concentrations was calculated at the exposure endpoint， and a "dose-toxicity" curve was drawn. The 10% lethal concentration （LC10） was calculated. Liver phenotype， acridine orange staining， and pathological tissue sections of liver-transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP））］ were used to confirm hepatotoxicity of EVO. On this basis， prednisolone was used to create a model of osteoporosis in zebrafish. The skull development， area of the skull stained by alizarin red， and cumulative optical density were used as indicators to evaluate the anti-osteoporotic activity of EVO in a safe dose. Based on network pharmacology， the mechanism of action of EVO in the treatment of osteoporosis was predicted and verified through Real-time PCR. ResultsThe LC10 of EVO on zebrafish （7 dpf） was determined to be 0.4 mg·L-1. Compared with the control group， sublethal concentrations （10=0.36 mg·L-1 and 1/2LC10=0.18 mg·L-1） significantly decreased the fluorescence area of zebrafish liver （P<0.05，P<0.01） and increased the number of liver cell apoptosis. The arrangement of liver tissue was disordered and loose， and the vacuole was obvious， especially in the 0.36 mg·L-1 group. Compared with the control group， under safe dose conditions， 0.08 and 0.02 mg·L-1 of EVO had no significant effect on the liver. Prednisolone administration significantly reduced the mineralization area and cumulative optical density of zebrafish skulls （P<0.01） compared with the control group. The mineralization area and cumulative optical density of zebrafish skulls in the 0.08 and 0.02 mg·L-1 groups of EVO were significantly increased compared with the model group （P<0.01）. Network pharmacology prediction suggested that EVO may regulate key targets such as avian sarcoma viral oncogene homolog （SRC）， signal transducer and activator of transcription 3 （STAT3）， interleukin-8 （CXCL8） and tyrosine kinase receptor 2 （ERBB2） to regulate signaling pathways related to lipid and atherosclerosis in diabetic complications， as well as the regulation of inflammatory mediators of tryptophan （TRP） channels. Real-time PCR experiment results indicated that EVO could regulate the above-mentioned targets， as well as genes related to osteoblasts and osteoclasts. ConclusionExcessive doses of EVO can lead to hepatotoxicity in zebrafish. Under safe dosage conditions， EVO can regulate relevant targets to exert anti-osteoporotic activity， providing a reference for the clinical safe use of EVO and ideas for the development of new drugs for osteoporosis.
