Effect of Malus asiatica Nakai Leaf Flavonoids on the Prevention of Esophageal Cancer in C57BL/6J Mice by Regulating the IL-17 Signaling Pathway

Background: The aim of this study was to observe the preventive effect of flavonoids extracted from Malus asiatica Nakai leaves (FMANL) on esophageal cancer in mice, especially the ability of FMANL to regulate the interleukin 17 (IL-17) signaling pathway during this process.

Materials and methods: The C57BL/6J mice were treated with 4-nitroquinoline N-oxide (4NQO) to induce esophageal cancer, and the visceral tissue index and the serum and esophageal tissue indexes of mice were used to verify the effect of FMANL.

Results: The experimental results showed that FMANL can effectively control the changes in visceral tissue caused by esophageal cancer. FMANL could increase the cytokine levels of interleukin 10 (IL-10), monocyte chemotactic protein 1 (MCP-1) and decrease the cytokine levels of tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), interleukin 6 (IL-6), and interleukin 12p70 (IL-12p70) in serum of mice with esophageal cancer. FMANL could also reduce CD3⁺, CD4⁺, and CD8⁺ and enhance CD19⁺ mouse peripheral blood lymphocytes. The results of qPCR and Western blot analysis showed that FMANL could down-regulate the mRNA and protein expression levels of IL-17, interleukin 23 (IL-23), interleukin 1 beta (IL-1β), chemokine (C-X-C) ligand 1 (CXCL1), chemokine (C-X-C) ligand 2 (CXCL2), S100 calcium-binding protein A8 (S100A8), S100 calcium-binding protein A9 (S100A9), matrix metalloprotein 9 (MMP-9), and matrix metalloprotein 13 (MMP-1) in mice with esophageal cancer. High-performance liquid chromatography (HPLC) detection showed that FMANL contained 10 chemicals, including rutin, hyperoside, isoquercitrin, dihydroquercetin, quercitrin, hesperidin, myricetin, baicalin, neohesperidin dihydrochalcone, and quercetin.

Conclusion: It could be concluded that FMANL can effectively prevent experimentally induced esophageal cancer in mice, and its effects might be obtained from 10 compounds present in FMANL.

Keywords: C57BL/6J mice; Malus asiatica Nakai leaves; esophageal cancer; flavonoid; mRNA IL-17 signaling pathway.