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Musa paradisiaca L. (Musaceae), a tropical plant named banana is used as food and as medicine in Brazil. Banana inflorescence, popularly known as mangará, presents several biological activities including anti-inflammatory effects. Here, we demonstrated the immunomodulatory activity of banana inflorescence extract (HEM) on a mice model of combined allergic rhinitis and asthma syndrome (CARAS) and in human macrophages. The HEM inhibited the eosinophil migration, production of cytokines as IL-4, IL-5, IL-13, and IL-17A dependent on IFN-ɣ production in the airway. The mechanism of the extract was, in part, by the NF-κB signaling pathway inhibition. Besides, the HEM decreased expression of the CD86 and HLA-DR receptors on human M1 macrophages independently of M2 modulation. Therefore, we infer that the inflorescence, a disposable material from the banana crops, has anti-allergic property in the CARAS model and modulates the human macrophages, characterizing it as biologically important material for the production of phytomedicine.