Uncovering the effects and molecular mechanism of Astragalus membranaceus (Fisch.) Bunge and its bioactive ingredients formononetin and calycosin against colon cancer: An integrated approach based on network pharmacology analysis coupled with experimental validation and molecular docking

Abstract

Colon cancer is a highly malignant cancer with poor prognosis. Astragalus membranaceus (Fisch.) Bunge (Huang Qi in Chinese, HQ), a well-known Chinese herbal medicine and a popular food additive, possesses various biological functions and has been frequently used for clinical treatment of colon cancer. However, the underlying mechanism is not fully understood. Isoflavonoids, including formononetin (FMNT) and calycosin (CS), are the main bioactive ingredients isolated from HQ. Thus, this study aimed to explore the inhibitory effects and mechanism of HQ, FMNT and CS against colon cancer by using network pharmacology coupled with experimental validation and molecular docking. The network pharmacology analysis revealed that FMNT and CS exerted their anticarcinogenic actions against colon cancer by regulating multiple signaling molecules and pathways, including MAPK and PI3K-Akt signaling pathways. The experimental validation data showed that HQ, FMNT and CS significantly suppressed the viability and proliferation, and promoted the apoptosis in colon cancer Caco2 and HT-29 cells. HQ, FMNT and CS also markedly inhibited the migration of Caco2 and HT-29 cells, accompanied by a marked increase in E-cadherin expression, and a notable decrease in N-cadherin and Vimentin expression. In addition, HQ, FMNT and CS strikingly decreased the expression of ERK1/2 phosphorylation (p-ERK1/2) without marked change in total ERK1/2 expression. They also slightly downregulated the p-Akt expression without significant alteration in total Akt expression. Pearson correlation analysis showed a significant positive correlation between the inactivation of ERK1/2 signaling pathway and the HQ, FMNT and CS-induced suppression of colon cancer. The molecular docking results indicated that FMNT and CS had a strong binding affinity for the key molecules of ERK1/2 signaling pathway. Conclusively, HQ, FMNT and CS exerted good therapeutic effects against colon cancer by mainly inhibiting the ERK1/2 signaling pathway, suggesting that HQ, FMNT and CS could be useful supplements that may enhance chemotherapeutic outcomes and benefit colon cancer patients.

Elucidation of the mechanism of action of ailanthone in the treatment of colorectal cancer: integration of network pharmacology, bioinformatics analysis and experimental validation

“…CRC constitutes a major health threat with high incidence and mortality rates ( Hu et al, 2023 ). Although AIL reportedly exhibits promising antitumor activity ( Zhuo et al, 2015 ; Ni et al, 2017 ; Yang et al, 2018 ; Liu et al, 2019 ), research regarding its role in CRC treatment is limited ( Ding et al, 2022 ).…”

Design, Synthesis, Biological Evaluation, and Molecular Docking Studies of Pleuromutilin Derivatives Containing Thiazole

“…In molecular docking, a higher number of hydrogen bonds and lower binding free energy values signify a stronger affinity between the ligand and receptor, leading to a more stable conformation. 33 Therefore, to gain insight into the potential interaction between compound 14 and the 50S ribosome, molecular docking analyses were conducted. The molecular docking results are illustrated in Figure 6.…”

A review of the botany, phytochemistry, traditional uses, pharmacology, toxicology, and quality control of the Astragalus memeranaceus

“…Tumors are classified as benign and malignant, and cancer is a type of malignant tumor that originates from epithelial tissue. According to the studies conducted in the last decade, FMN and CAL can treat oncological diseases, including lung ( Yang et al, 2014 ), breast ( Yu et al, 2017 ), colorectal ( Hu et al, 2023 ), ovarian ( Yao et al, 2019 ), and gastric cancers ( Zhou et al, 2015 ), via various molecular pathways. Their mechanism of anti-tumor action includes inhibition of cell proliferation, influence on the cell cycle, and induction of apoptosis.…”