Exploration of the Mechanism of Kaempferol in the Treatment of Cervical Cancer-based on Metabolomics and Network Pharmacology

Abstract

Background: Cervical cancer is a prevalent malignancy among women globally. Objective: We aimed to uncover the mechanism of action of kaempferol in the treatment of cervical cancer using an integrated approach that combines metabolomics with network pharmacology. Methods: Initially, we investigated the specific metabolites and potential pathways influenced by kaempferol in the pathological progression of cervical cancer, employing UHPLC-Q-Orbitrap MS metabolomics. In addition, network pharmacology analysis was performed to ascertain the pivotal targets of kaempferol in the context of CC therapy. Results: Metabolomics analysis indicated that the therapeutic effect of kaempferol on cervical cancer is primarily associated with 11 differential metabolites and 7 metabolite pathways. These pathways include arginine and proline metabolism, the tricarboxylic acid cycle, phenylalanine, tyrosine, and tryptophan biosynthesis, fatty acid biosynthesis, glycerophospholipid metabolism, pantothenate and CoA biosynthesis, and tyrosine metabolism. Additionally, kaempferol was found to regulate 3 differential metabolites, namely palmitic acid, citric acid, and L-tyrosine, by directly targeting 7 specific proteins, including AKR1B1, CS, EGFR, PLA2G1B, PPARG, SLCO2B1, and SRC. Furthermore, molecular docking demonstrated strong binding affinities between kaempferol and 7 crucial targets. Conclusion: This study elucidates the intricate mechanisms by which kaempferol acts against cervical cancer. Furthermore, this research offers a novel approach to investigating the potential pharmacological mechanisms of action exhibited by natural compounds.