Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidii Fructus in Treating Colorectal Cancer

Zhihui Wei; Xiaoyun Zhang; Antang Peng; Chenxu Liu; Yajing Zhang; Xuhong Duan; Jianying Pang

doi:10.2174/0113862073273396231010102606

Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidii Fructus in Treating Colorectal Cancer

Comb Chem High Throughput Screen. 2023 Oct 11. doi: 10.2174/0113862073273396231010102606. Online ahead of print.

Authors

Zhihui Wei¹, Xiaoyun Zhang², Antang Peng³, Chenxu Liu⁴, Yajing Zhang⁴, Xuhong Duan⁴, Jianying Pang⁴

Affiliations

¹ China Pharmaceutical University School of Pharmacy Nanjing China.
² Hebei University of Chinese Medicine College of Integrated Chinese and Western Medicine Shijiazhuang China.
³ Shijiazhuang Fourth Hospital The Traditional Chinese Medicine Hospital of Shijiazhuang Shijiazhuang China.
⁴ Hebei University of Chinese Medicine College of Pharmacy Shijiazhuang China.

PMID: 37861043
DOI: 10.2174/0113862073273396231010102606

Abstract

Aims: Cnidii Fructus (CF) is known for its antibacterial, anti-inflammatory, and antitumor properties, as well as its activities against kidney deficiency and impotence. In this study, we aimed to explore the anti-CRC cancer effect and molecular mechanism of CF via network pharmacology and in vitro antitumor experiments.

Methods: Network pharmacology was used to investigate the anti-CRC mechanism of CF. First, a series of databases was used to screen the active phytochemical targets and anti-CRC core targets. Then, the GO and KEGG pathways were analyzed to predict possible mechanisms. Molecular docking analysis explore core targets-phytochemicals interactions. In vitro antitumor experiments were carried on verifying anti-CRC mechanism of CF.

Results: In this study, 20 active ingredient targets and 50 intersecting targets were analyzed by Cytoscape software 3.9.1 to obtain the core genes and phytochemicals. Then, the GO and KEGG pathways of 50 intersecting targets were analyzed to predict possible mechanisms. The results from GO and KEGG indicated that CF has significant antitumor efficacy, which involves many signaling pathways, such as PI3K/AKT and p53. The five core targets and five core phytochemicals were screened for molecular docking to show protein-ligand interactions. According to the results of molecular docking, the compound O-acetylcolumbianetin was selected for the anti- CRC functional verification in vitro. MTT assay showed that O-acetylcolumbianetin significantly inhibited the proliferation of colorectal HCT116 cells in a time- and quantity-dependent manner. O-acetylcolumbianetin can promote the expression of CASP3 protein, induce HCT116 cells apoptosis, thus exert anti-CRC effect.

Conclusion: This study preliminarily verified the anti-CRC effect and molecular mechanism of CF and provided a reference for Traditional Chinese Medicine anti-tumor subsequent research.

Keywords: Cnidii Fructus; network pharmacology; active phytochemicals; molecular mechanism; colorectal cancer.