Study on the Mechanism of the Flavonoids from the New
10.13748/j.cnki.issn1007-7693.20232688
- VernacularTitle:基于网络药理学研究新“浙八味”衢枳壳黄酮抗肝细胞癌的作用机制
- Author:
Liang GAO
1
,
2
;
Yalin ZHANG
2
;
Yuhan WU
2
;
Jiahui SHAO
2
;
Hui ZHANG
1
;
Yidan SHAO
3
;
Yaping XU
4
;
Jianping JIANG
2
,
5
Author Information
1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
2. School of Medicine, Hangzhou City University, Hangzhou 310015, China
3. Hangzhou Xixi Hospital, Hangzhou 310023, China
4. The First Affliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China
5. Affiliated Hospital, Hangzhou City University, Hangzhou 311300, China
- Publication Type:Journal Article
- Keywords:
Quzhou Fructus Aurantii;
flavonoids;
network pharmacology;
hepatocellular carcinoma;
apoptosis;
PRKCA
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(2):166-176
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To explore the mechanisms of the flavonoids from new "Zhe Eight Flavors" Quzhou Fructus Aurantii(PTFC) against hepatocellular carcinoma based on the prediction of network pharmacology and experimental verification.
METHODS
From TCMSP, TCMID, ETCM, BATMAN-TCM and SwissTargetPrediction databases, the potential target proteins of PTFC, including naringin, narirutin and neohesperidin were collected. Based on the GeneCards, CTD, Disgenet, and OMIM databases, a set of target proteins for hepatocellular carcinoma was constructed. Taking the intersection of potential target proteins of PTFC and target proteins of hepatocellular carcinoma, key target proteins were obtained and a protein-protein interaction network was established. Besides, GO function and KEGG pathway enrichment analysis on the core target proteins was performed and a Compounds-Targets-Pathways-Disease network was constructed. Through proliferation, cloning, wound healing, and migration experiments, the effects of PTFC on the viability of HepG2 liver cancer cells were analyzed. Using fluorescence probe staining the impacts of PTFC on the mitochondrial membrane potential and apoptosis of HepG2 were observed. Finally, the validation of the regulatory effect of PTFC on the key predicted target PRKCA were carried out through RT-qPCR.
RESULTS
Based on network pharmacology, a total of 217 potential target proteins for PTFC were screened, with 59 intersecting target proteins related to diseases, including ALB, ESR1, PRKCA, and others. GO functional and KEGG pathway enrichment analysis revealed that the PTFC target proteins were involved in 193 biological processes and 13 cancer-related signaling pathways. Experimental results demonstrated that PTFC could impact the proliferation, cloning, wound healing, and migration abilities of liver cancer cells, leading to a decrease in mitochondrial membrane potential and promoting cell apoptosis. The results of RT-qPCR confirmed a significant downregulation of PRKCA expression by PTFC, validating the predictions made by network pharmacology analysis.
CONCLUSION
This study has revealed the potential molecular mechanism of PTFC treating hepatocellular carcinoma via the PRKCA target, laying the foundation for clinical application of PTFC.
