Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), State Ethnic Affairs Commission, 100081, Beijing, China; College of Pharmacy, Minzu University of China, Beijing, 100081, China.
Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), State Ethnic Affairs Commission, 100081, Beijing, China; Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, 100081, Beijing, China.
J Ethnopharmacol. 2022 Nov 15;298:115609. doi: 10.1016/j.jep.2022.115609. Epub 2022 Aug 8.
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.
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.
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.
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.
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.
银杏（Ginkgo biloba L.）是中国特有的珍稀树种。银杏作为一种传统中药，具有悠久的历史，作用于心肺经络，据报道对非小细胞肺癌有显著疗效。然而，这种代谢作用的机制尚不清楚。
鉴定银杏提取物中可能对非小细胞肺癌有作用的活性成分及其代谢调节机制。
本研究采用 LC-MS/MS 法研究银杏提取物的化学成分。采用网络药理学方法鉴定治疗非小细胞肺癌有潜在价值的活性成分。采用 CCK-8 和细胞凋亡实验评价抗肿瘤活性。进一步采用非靶向代谢组学、靶向代谢组学和 Western blot 实验探讨活性成分的代谢调节机制。
网络药理学和银杏提取物成分分析鉴定出 4 种银杏内酯，对非小细胞肺癌有显著影响。采用 CCK-8 和细胞凋亡实验评价其在 A549 细胞中的增殖抑制活性。代谢组学结果表明，银杏内酯对与一碳代谢相关的代谢途径如嘌呤代谢、谷胱甘肽代谢和蛋氨酸循环具有显著的调节作用。进一步对一碳代谢的靶向代谢组学分析发现，银杏内酯可能显著影响 A549 细胞中多种代谢物的含量，包括嘌呤、S-腺苷甲硫氨酸、S-腺苷同型半胱氨酸和谷胱甘肽上调，而腺苷、四氢叶酸和 10-甲酰四氢叶酸显著减少。值得注意的是，二氢叶酸还原酶（DHFR）和亚甲基四氢叶酸脱氢酶（MTHFR）在银杏内酯处理后发生改变。
本体外研究表明，银杏内酯可能通过靶向一碳代谢抑制 A549 细胞的生长。本研究还表明，代谢组学结合网络药理学是鉴定中药活性成分及其代谢机制的有力工具。
