Figure 2.

Cellular mechanisms of the anti-inflammatory, immunomodulatory and antioxidant effects exerted by hop compounds. Polyphenols extracted from H. lupulus such as xanthohumol, isoxanthohumol and bitter acids can interfere with intracellular immune signaling pathways at different levels. Due to the inhibition of TLR4 activation through preventing the association of TLR4 dimers with the co-stimulatory molecule MD2, NF-κB nuclear translocation was prevented. Hop compounds inhibit NF-κB signaling pathway due to both, the inhibition of TLR4 activation through preventing the association of TLR4 dimers with the co-stimulatory molecule MD2, and in a TLR-independent fashion. Hop compounds can inhibit other pro-inflammatory signaling pathways driven by STAT-1 and IRF-1. Thus, reducing the expression of the subset of pro-inflammatory mediators such as IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α, inflammasome subunits, nitric oxide, cyclooxygenases, and prostaglandin production, adhesion molecules such as ICAM-1, MCP-1, and MIP-1. Simultaneously, hop compounds promote microglial phagocytic activity together with the switching to M2 phenotype. In different cell types, hop compounds also prevent fibrotic processes by reducing the expression of α-SMA or TGF-β. However, hop compounds also promote the pro-inflammatory and cytotoxic responses from lymphocytes to elicit anti-tumor responses. Finally, in many cases, the anti-inflammatory effects of hop compounds are accompanied by the activation of the antioxidant response regulator, Nrf-2, and the increase in the production of HO-1, NQO-1, GST, GCL, Trx-1 and TrxR-1.