The mechanism of flavonoids from Cyclocarya paliurus on inhibiting liver cancer based on in vitro experiments and network pharmacology

Jinggang Mo; Yingpeng Tong; Junxia Ma; Kunpeng Wang; Yifu Feng; Liezhi Wang; Hao Jiang; Chong Jin; Junmin Li

doi:10.3389/fphar.2023.1049953

The mechanism of flavonoids from Cyclocarya paliurus on inhibiting liver cancer based on in vitro experiments and network pharmacology

Front Pharmacol. 2023 Feb 3:14:1049953. doi: 10.3389/fphar.2023.1049953. eCollection 2023.

Authors

Jinggang Mo¹, Yingpeng Tong², Junxia Ma³, Kunpeng Wang¹, Yifu Feng¹, Liezhi Wang¹, Hao Jiang¹, Chong Jin¹, Junmin Li^{2

3}

Affiliations

¹ Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang, China.
² School of Advanced Study, Taizhou University, Taizhou, China.
³ Zhejiang Provincial Key Laboratory of Evolutionary Ecology and Conservation, Taizhou University, Taizhou, China.

Abstract

Introduction: Cyclocarya paliurus (Batal.) Iljinsk., a subtropical tree belonging to the family Juglandaceae, is rich in polysaccharides, flavonoids, and terpenoids. It has important pharmacological effects such as lowering blood lipids, blood sugar, and blood pressure. However, little has been discerned regarding anti tumor effects and their potential mechanisms. Method: In vitro cell culture experiments were used to test the effect of C. paliurus total flavonoids (CTFs) extract on apoptosis mechanisms in HepG2 cells. Network pharmacology was applied to further explore the effects of CTFs on liver cancer as well as the mechanisms through which these effects might be achieved. Both 3 hydroxyflavone and luteolin were randomly selected to verify the effect on inducing apoptosis and inhibiting the proliferation of HepG2 cells. Results and Discussion: Network pharmacological analysis was applied to these 62 compounds and their targets, and 13 flavonoids were further screened for their potential anti liver cancer activity. These 13 flavonoids included: tangeretin, baicalein, 7,3'-dihydroxyflavone, velutin, 3-hydroxyflavone, chrysin, kumatakenin, tricin, luteolin, chrysoeriol, apigenin, pinocembrin, and butin. Together, these flavonoids were predicted to interact with AKT1, MAPK3, PIK3CA, EGFR, MAP2K1, SRC, IGF1R, IKBKB, MET, and MAPK14. It was predicted that the inhibitory effect on hepatocellular carcinoma would be accomplished by regulation of core proteins relating to such KEGG pathways as cancer, PI3K-Akt, proteoglycans in cancer, microRNAs in cancer, and endocrine resistance via core target proteins. Both 3-hydroxyflavone and luteolin were demonstrated to induce apoptosis and inhibit the proliferation of HepG2 cells. Our study provides scientific evidence supporting the use of CTFs for the treatment of liver cancer.

Keywords: Cyclocarya paliurus; active ingredients; apoptosis; flavonoids; in vitro experiments; liver cancer; network pharmacology.

Grants and funding

This work was supported by Jiebang Guashuai Program in Traditional Chinese Medicine Industry of Pan’an County, Zhejiang Province Public Welfare Technology Application Research Project (No. LGF21H160022), Natural Science Foundation of Zhejiang Province (No. LQ22H160055), Science and Technology Plan Project of Taizhou (No. 21ywb26, 21ywb29,22ywa14 and 22ywb26), Medical Science and Technology Project of Zhejiang Province (No. 2017KY711).