Cycas revoluta leaves: As a potential flavonoids source for targeted regulation of immune-related markers in lung adenocarcinoma

Abstract

Cycas revoluta Thunb. (CR) is a widely distributed ornamental and economical plant, and its seeds are important sources of starch and β-cyclodextrin production. However, the medicinal value of CR leaves should also be considered, because flavonoids in CR leaves could represent a possible substance basis for the treatment of lung adenocarcinoma (LUAD). Oxidative stress (OS) and inflammatory immune response (IIR) have been reported to be associated with tumorigenesis and tumor progression. In this study, for the first time, Ultra-high-performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry (UPLC-Q Exactive Orbitrap-MS) method was used to systematically analyze the chemical profile of CR leaves, and characteristic fragment ions and fragmentation patterns of flavonoids obtained from CR. leaves was analyzed. Subsequently, network pharmacology and molecular docking methods were applied to explore the underlying central targets and related pathways of the targeted regulation of OS and IIR by flavonoids in CR leaves. Consequently, A total of 62 components were characterized from CR. including 10 flavonoids, which were (-)-epigallocatechin, amentoflavone, bilobetin, catechin, ginkgetin, hinokiflavone, naringenin, podocarpusflavone A, sciadopitysin, and vitexin respectively. The hub targets of these 10 flavonoids from CR in treating LUAD was narrowed in Fms-like tyrosine kinase 3 (FLT3), Cyclin A2 (CCNA2), Cyclin B1 (CCNB1), Insulin-like growth factor-binding protein 3 (IGFBP3), Peroxisome proliferator-activated receptor-γ (PPARG), Catalase (CAT), and Myeloid cell leukemia-1 (MCL1). Among them, amentoflavone and podocarpusflavone A have shown great therapeutic potential, while CAT and CCNA2 can be used as potential markers for future studies of flavonoids in CR leaves against LUAD from the perspective of OS and IIR. Taken together, the results showed that flavonoids in CR leaves are potential sources of anti-LUAD compounds by targeting OS and IIR, which will offer a scientific insight for the exploitation and application of CR leaves as functional resources and also provide methodological references for the deeper development of other cash crops.