Mechanism of ginkgo flavonoid aglycone against doxorubicin-induced cardiotoxicity
- VernacularTitle:银杏黄酮苷元减轻多柔比星心脏毒性的作用机制
- Author:
Ying CAI
1
;
Li QIAN
2
;
Kailiang WANG
1
;
Qin LI
3
;
Chunhua LIU
4
;
Jia SUN
5
;
Jie PAN
4
;
Yongjun LI
6
;
Yuan LU
5
Author Information
1. Guizhou Provincial Key Laboratory of Pharmaceutics & State Key Laboratory of Functions and Applications of Medicinal Plants，Guizhou Medical University，Guiyang 550004，China;School of Pharmacy，Guizhou Medical University，Guiyang 550004，China
2. School of Pharmacy，Guizhou Medical University，Guiyang 550004，China
3. Key Laboratory of Basic Pharmacology of Ministry of Education，Zunyi Medical University，Guizhou Zunyi 563006，China
4. Engineering Research Center for the Development and Application of Ethnic Medicine and TCM （Ministry of Education），Guizhou Medical University，Guiyang 550004，China
5. Guizhou Provincial Key Laboratory of Pharmaceutics & State Key Laboratory of Functions and Applications of Medicinal Plants，Guizhou Medical University，Guiyang 550004，China
6. School of Pharmacy，Guizhou Medical University，Guiyang 550004，China;Engineering Research Center for the Development and Application of Ethnic Medicine and TCM （Ministry of Education），Guizhou Medical University，Guiyang 550004，China
- Publication Type:Journal Article
- Keywords:
ginkgo flavonoid aglycone;
doxorubicin;
cardiotoxicity;
metabolomics
- From:
China Pharmacy
2024;35(6):659-664
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the potential mechanism of the effect of ginkgo flavone aglycone （GA） against doxorubicin （DOX）-induced cardiotoxicity. METHODS The male ICR mice were randomized into control group （CON group）， model group （DOX group） and GA+DOX group （GDOX group）， with 12 mice in each group. The DOX group was injected with DOX solution at a dose of 3 mg/kg via tail vein every other day， and the GDOX group was given GA suspension intragastrically at a dose of 100 mg/kg every day+DOX solution at a dose of 3 mg/kg via tail vein every other day， for 15 consecutive days. After the end of administration， the serum levels of aspartate aminotransferase（AST）， creatine kinase（CK）， creatine kinase isoenzyme（CK- MB） and lactate dehydrogenase（LDH） in mice were detected in each group. Based on the metabolomics method， UHPLC-Q- Exactive Orbitrap HRMS method was used； based on principal component analysis （PCA） and orthogonal partial least squares- discriminant analysis （OPLS-DA）， the differentially expressed metabolites （DEMs） were screened using the criteria of variable importance in the projection≥1， fold change of peak area＞1 and P＜0.05； biological analysis was conducted based on databases such as HMDB and PubChem. RESULTS Compared with CON group， serum levels of AST， CK， CK-MB and LDH were increased significantly in DOX group （P＜0.05）； compared with DOX group， the serum levels of the above indicators （except for CK-MB） were decreased significantly in GDOX group （P＜0.05）. PCA and OPLS-DA showed that myocardial tissue samples of CON group， DOX group and GDOX group were isolated completely. After database matching， 37 common DEMs were identified， among which 17 DEMs were significantly up-regulated in the DOX group and significantly down- regulated in the GDOX group， and 8 DEMs were significantly down-regulated in the DOX group and significantly up-regulated in the GDOX group； pathway enrichment involved the biosynthesis of unsaturated fatty acids， arachidonic acid metabolism， linoleic acid metabolism， taurine and hypotaurine metabolism； the key metabolites in the above pathways included docosahexaenoic acid， arachidonic acid， phosphatidylcholine （16∶0/18∶3） and taurine. CONCLUSIONS GA may regulate the biosynthesis of unsaturated fatty acids， arachidonic acid metabolism and other metabolic pathways by acting on the core metabolites such as docosahexaenoic acid and arachidonic acid， thus alleviating the cardiotoxic effects of DOX.
