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[Display omitted] • Syzygium aromaticum aqueous extract (AE) enhanced innate immunity by inducing macrophages M1 polarization. • AE inhibited the Nrf2/HO-1 signal while activated the TLR4/Myd88 mediated NF-κB and MAPK pathways in macrophages. • AE alleviated Helicobacter pylori infection-related inflammation. Previous studies suggested that Syzygium aromaticum dried buds (S. aromaticum), which is an edible and medicinal herb, possess potential effect on innate immunity and Helicobacter pylori (H. pylori) infection-related inflammation, but the specific action and especially the molecular mechanism have not been well elucidated. The objective of this work was to further explore the effects of Syzygium aromaticum aqueous extract (AE) on innate immunity and H. pylori related-inflammation, especially the potential molecular mechanisms involved. In order to accomplish this, analyses of the phagocytic rate, NO content, ROS level, as well as ELISA, RT-qPCR, and Western blotting et al. assays were carried out. Results indicated that AE increased phagocytic rate, ROS, and cytokine expression levels, meanwhile activated TLR4/MyD88 mediated NF-κB and MAPK pathways and decreased Nrf2/HO-1 signaling. AE also prevented the release of pro-inflammatory substances made by H. pylori -infected RAW 264.7 and GES-1 cells. All things considered, it was shown that AE's ability to boost innate immunity involves inducing macrophage M1 polarization by increasing TLR4/MyD88-mediated NF-κB and MAPK pathways and blocking Nrf2/HO-1 signaling. Additionally, by lowering the production of pro-inflammatory molecules, AE can lessen the inflammation brought on by H. pylori. Considering that S. aromaticum is an edible herbal medicine with immune-enhancing activity and good safety, it deserves further study and utilization for treating diseases including H. pylori infection-related disorders. [ABSTRACT FROM AUTHOR]