The regulation of the TLR4/NF-κB and Nrf2/HO-1 signaling pathways is involved in the inhibition of lipopolysaccharide-induced inflammation and oxidative reactions by morroniside in RAW 264.7 macrophages

• Published in: Archives of biochemistry and biophysics 2021-07, Vol.706, p.108926-108926, Article 108926
• Main Authors: Park, Cheol, Cha, Hee-Jae, Lee, Hyesook, Kim, Gi-Young, Choi, Yung Hyun
• Format: Article
• Language: English
• Subjects: Inflammation; Morroniside; Nrf2/HO-1; Oxidative stress; TLR4/NF-κB
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2021.108926

Morroniside, a major iridoid glycoside isolated from Cornus officinalis, has a variety of beneficial pharmacological properties. Although morroniside has recently been reported to exhibit anti-inflammatory and antioxidant effects, the detailed mechanism has not yet been fully elucidated. In this study, we investigated the inhibitory effect of morroniside on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Our results indicated that morroniside pretreatment significantly inhibited the LPS-induced phagocytic activity and release of pro-inflammatory factors, which was associated with blocking the expression of their regulatory genes. Morroniside also markedly suppressed the expression of myeloid differentiation factor 88 as well as Toll-like receptor 4 (TLR4), and attenuated the translocation of nuclear factor-κB (NF-κB) to the nucleus in LPS-treated RAW 264.7 macrophages. Furthermore, morroniside prevented the binding of LPS to the TLR4 on the cell surface. In addition, morroniside abolished reactive oxygen species (ROS) generation, and enhanced the expression of heme oxygenase-1 (HO-1) following activation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the morroniside-mediated inhibition of inflammatory response in LPS-treated RAW 264.7 macrophages. In conclusion, our findings suggest that morroniside exerts LPS-induced anti-inflammatory and antioxidant effects by targeting the TLR4/NF-κB and Nrf2/HO-1 signaling pathways in RAW 264.7 macrophages. Taken together, our findings suggest that morroniside interacted structurally and electrochemically with TLR4/MD2 complex, consequently can be a potential functional agent to prevent inflammatory and oxidative damage. [Display omitted] •Morroniside has an anti-inflammatory and antioxidant effect in RAW 264.7 macrophages.•Morroniside inhibits LPS-induced activation of NF-κB in RAW 264.7 macrophages.•Morroniside diminishes LPS-induced expression of TLR4 and MyD88 and prevents LPS from binding to the TLR4.•Morroniside activates the Nrf2/HO-1 signaling pathway in LPS-treated RAW 264.7 macrophages.