Evaluation of Anti-osteoporosis Activity and Hepatotoxicity of Xianling Gubao Based on Zebrafish Model
10.13422/j.cnki.syfjx.20241819
- VernacularTitle:基于斑马鱼模型的仙灵骨葆抗骨质疏松（效）-肝损伤（毒）转化机制
- Author:
Qiuman LI
1
;
Yue QIAN
1
;
Zixuan ZHU
1
;
Yuan SONG
1
;
Qian DENG
2
;
Shengyun DAI
3
;
Chongjun ZHAO
4
Author Information
1. School of Acupuncture-Moxibustion and Tuina， Beijing University of Chinese Medicine， Beijing 100105， China
2. School of Clinical Medicine， Nanjing University， Nanjing 210093， China
3. National Institute for Food and Drug Control， Beijing 100050， China
4. Beijing Key Laboratory of Quality Evaluation of Traditional Chinese Medicine， School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 102488， China
- Publication Type:Journal Article
- Keywords:
Xianling Gubao;
zebrafish;
hepatotoxicity;
osteoporosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(4):87-94
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the association and translational mechanism between the hepatotoxicity of Xianling Gubao （XLGB） and its treatment of osteoporosis based on a zebrafish model. MethodsZebrafish were randomly selected four days after fertilization （4 dpf） and exposed to different concentrations of XLGB （0.7，0.35 mg·L-1） for 96 h. At the endpoint of the exposure， the mortality rates of zebrafish in the treatment groups of different concentrations were counted， and the "dose-toxicity" curves were plotted. The 10% sublethal concentration （LC10） was calculated. The liver area， acridine orange staining， and pathological tissue sections of transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP）］ were used as indicators to confirm the hepatic damage caused by the sublethal concentration of XLGB. By using the prednisolone （PNSL）-induced osteoporosis model of zebrafish， the anti-osteoporosis activity of XLGB was evaluated by using the area of skull stained by alizarin red and the cumulative optical density value as indicators. Then， the toxicity difference of XLGB on the liver of zebrafish in healthy and osteoporotic states was compared， and the mechanism of the translational action of the toxicity of XLGB was predicted based on network pharmacology and real-time polymerase chain reaction（Real-time PCR）. ResultsThe LC10 of XLGB on zebrafish （8 dpf） was 0.7 mg·L-1. Compared with the blank group， the sublethal concentration （LC10=0.7 mg·L-1， 1/2 LC10=0.35 mg·L-1） of XLGB induced an increase in the number of apoptosis of hepatocytes in a dose-dependent manner， and the tissue arrangement of the liver was disordered and loose. The vacuoles were obvious， and the fluorescence area of the liver was significantly reduced （P<0.01）. Compared with the blank group， the mineralized area and cumulative optical density value of zebrafish skull in the PNSL model group were significantly reduced （P<0.01）， and those in the 0.7，0.35 mg·L-1 XLGB treatment group were significantly increased compared with the model group （P<0.01）. Most importantly， 0.7 mg·L-1 XLGB had no significant effect on the liver of zebrafish in the osteoporosis disease model compared with the blank group. The results of network pharmacology and real-time PCR experiments showed that the toxic transformation of XLGB might be related to the differences in the expression levels of key targets， such as tumor protein 53 （TP53）， cysteine aspartic acid specific protease-3（Caspase-3）， interleukin（IL）-6， and alkaline phosphatase（ALP） in different organismal states. ConclusionUnder certain conditions， XLGB has hepatotoxicity in normal zebrafish， but under osteoporotic conditions， XLGB not only exerts significant anti-osteoporosis activity but also alleviates hepatotoxicity significantly， which provides a reference for the safe clinical use of XLGB and real evidence for the theories of traditional Chinese medicine of attacking poison with poison and of treating disease with corresponding drugs without damage to the body.
