Integrated Network Pharmacology and Metabolomics to Dissect the Mechanisms of Naringin for Treating Cervical Cancer.

Abstract

Cervical cancer is one of the malignant cancers with high mortality among women worldwide. Although vaccines and early detection have reduced cervical cancer mortality, it remains a malignancy with a high mortality rate in women. We aimed to develop a novel integrated strategy that combines metabolomics with network pharmacology to explore the therapeutic mechanisms of naringin in cervical cancer. The mechanism of naringin intervention in cervical cancer was initially clarified by metabolomics and network pharmacology. The method of LC-MS and network pharmacology for the detection and identification of potential biomarkers and the mechanisms of action of naringin was used. The metabolites were detected and identified based on ultra-high-performance liquid chromatography coupled with Quadrupole- Exactive Orbitrap MS (UHPLC-Q-Exactive Orbitrap MS) and followed by the network pharmacology analysis. In network pharmacology, naringin played a synergetic role through regulatory shared pathways, such as steroid hormone biosynthesis, sphingolipid signaling pathway and arachidonic acid metabolism, etc. Besides, the metabolomics analysis showed that 20 differential metabolites and 10 metabolic pathways were mainly involved in the therapeutic effect of naringin on cervical cancer. The result showed that naringin treatment for cervical cancer mainly occurs through the following metabolic pathways: amino acid metabolism and arachidonic acid metabolism. This work provided valuable information and a scientific basis for further studies of naringin in the treatment of cervical cancer.