Metabolomics and integrated network pharmacology analysis reveal that ginkgolides act as potential active anticancer components by regulating one-carbon metabolism. (15th November 2022)

• Record Type: Journal Article
• Authors: Zhou, Junyao; Qian, Mingmin; Li, Chenxi; Zhou, Wenbin; Yao, Lan; Chen, Yanhua; Abliz, Zeper
• Is Part Of: Journal of ethnopharmacology. Volume 298(2022)
• Publication Date: 2022-11-15
• Subjects: Ginkgolides -- Non-small cell lung cancer -- Cell proliferation -- Metabolomics -- One carbon metabolism; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115609
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Ginkgo biloba L. is a rare tree species unique to China. Ginkgo biloba is a traditional Chinese medicinal with a long history, acting on the heart and lung meridians, and has been reported to have a significant effect on non-small cell lung cancer. However, the mechanism underlying this metabolic effect is poorly understood. Aim of the study: To identify the active components of Ginkgo biloba extract that may have effects on non-small cell lung cancer and their mechanisms of metabolic regulation. Materials and methods: In this study, LC-MS/MS was used to investigate the chemical constituents of Ginkgo biloba extract. Network pharmacology was used to identify the active components potentially valuable in the treatment of non-small cell lung cancer. Antitumor activity was evaluated using CCK-8 and apoptosis assays. The mechanisms of metabolic regulation by the active components were further explored using untargeted metabolomics, targeted metabolomics, and western blot experiments. Results: Network pharmacology and component analysis of Ginkgo biloba extract identified four ginkgolides that significantly affect non-small cell lung cancer. Their antiproliferative activity in A549 cells was evaluated using CCK-8 and apoptosis assays. The metabolomics results indicated that the ginkgolides had a significant regulatory effect on metabolic pathways related to one-carbon metabolisms, such as purine metabolism, glutathione metabolism, and the methionine cycle. Further targeted metabolomics analysis on one-carbon metabolism found that the ginkgolides may significantly affect the content of multiple metabolites in A549 cells, including purine, S-adenyl methionine, S-adenylyl homocysteine, and glutathione upregulated, and adenosine, tetrahydrofolate, and 10-Formyl-tetrahydrofolate significantly decreased. Notably, dihydrofolate reductase (DHFR) and methylenetetrahydrofolate dehydrogenases (MTHFR) were found to be altered after the treatment of ginkgolides. Conclusion: This in vitro study indicated that ginkgolides might inhibit the growth of A549 cells by targeting one-carbon metabolism. This study also demonstrated that metabolomics combined with network pharmacology is a powerful tool for identifying traditional Chinese medicines' active components and metabolic mechanisms. Graphical abstract: Image 1