Idiosyncratic hepatotoxicity evaluation of Cortex Dictamni based on immune stress
10.16438/j.0513-4870.2018-1045
- VernacularTitle:基于免疫应激的白鲜皮致特异质肝损伤评价研究
- Author:
Wei SHI
1
,
2
,
3
;
Yuan GAO
3
,
4
,
5
;
Yu-ming GUO
3
,
4
;
Guang XU
3
,
4
;
Zhi-lei WANG
3
,
4
,
6
;
Nan QIN
1
,
2
,
3
;
Zhao-fang BAI
3
,
4
;
Xiao-he XIAO
3
,
4
Author Information
1. School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330000, China
2. China Military
3. Institute of Chinese Medicine, the Fifth Medical Centre, Chinese PLA People's Liberation Army General Hospital, Beijing 100039, China
4. China Military
5. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China
6. College Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Publication Type:Research Article
- Keywords:
italic>Cortex Dictamni;
idiosyncratic hepatotoxicity;
immune stress;
lipopolysaccharide;
network pharmacology
- From:
Acta Pharmaceutica Sinica
2019;54(4):678-686
- CountryChina
- Language:Chinese
-
Abstract:
Using the idiosyncratic lipopolysaccharide (LPS)-mediated hepatotoxicity model as a positive control, liver injury induced by Cortex Dictamni aqueous extract (AE) or Cortex Dictamni ethanol extracts (EE) was evaluated. Idiosyncratic hepatotoxicity model was established in rats [Institutional Animal Care and Use Committee (IACUC)-2018-008] by injecting LPS at a dosage of 2.8 mg·kg-1. Rats were randomly divided into 10 groups. The plasma levels of liver function biomarkers such as alanine transaminase (ALT), aspartate aminotransferase (AST) were measured. Histological changes (HE staining), hepatocellular apoptosis and the content of cytokines of liver were measured. Network pharmacology was used to analyze the relationship between chemical components and immunity in Cortex Dictamni. Compared with the control group, the doses (25, 50 g·kg-1) of AE or EE had no significant changes in ALT, AST and liver pathology (P>0.05). The doses of 4.2 g·kg-1 of AE or EE+LPS groups exhibited an elevation in ALT, AST and serum cytokines (P<0.01). Disorder of liver lobular arrangement and irregular island-like or massive necrosis of liver cells were observed in these groups. Network pharmacology shows that Cortex Dictamni may directly or indirectly participate in the process of immunomodulation. We found that Cortex Dictamni regulated 15 core targets and affected 19 pathways, including apoptosis, TNF-α, NF-kappa B signaling pathways. These results suggest that Cortex Dictamni can induce idiosyncratic hepatotoxicity and the water extract can induce more serious liver injury then ethanol extract of Cortex Dictamni. These findings provide a reference for elucidating the idiosyncratic hepatotoxicity induced by Cortex Dictamni.
