A novel marine halophenol derivative attenuates lipopolysaccharide-induced inflammation in RAW264.7 cells via activating phosphoinositide 3-kinase/Akt pathway

• Published in: Pharmacological reports Vol. 72; no. 4; pp. 1021 - 1031
• Main Authors: Yang, Fan, Cai, Hong-Hong, Feng, Xiu-E, Li, Qing-Shan
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2020
• Subjects: Drug Safety and Pharmacovigilance; Medicine; Pharmacotherapy; Pharmacy; RAW264.7 cells; PI3K/Akt pathway; LM49; Anti-inflammation
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1007/s43440-019-00018-9

Background 2,4′,5′-Trihydroxyl-5,2′-dibromo diphenylmethanone (LM49), a novel active halophenol derivative synthesized by our group from marine plants, exhibits strong anti-inflammatory activities. However, molecular machineries involved in its effect have not been fully identified. The study was aimed to investigate the anti-inflammatory effect of LM49 on lipopolysaccharide (LPS)-stimulated RAW264.7 cells and its underlying mechanism. Methods RAW264.7 cells were treated with LPS (10 μg/mL) and then exposed to different concentrations of LM49 (i.e., 5, 10, and 15 μM) for 24 h. Cytokine release in culture medium of RAW264.7 cells was measured by enzyme-linked immunosorbent assay (ELISA). Phagocytic capacity (FITC–dextran uptake) was determined by flow cytometry. The protein level of phosphoinositide 3-kinase (PI3K), AKT and p-AKT was measured by western blot analysis. Results Our findings revealed that LM49 reduced the production and mRNA levels of cytokines related to inflammation such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α), and increased the level of IL-10, an anti-inflammatory cytokine. In addition, LM49 decreased the production of nitric oxide and reactive oxygen species. Moreover, flow cytometry showed that LM49 significantly enhanced the phagocytic capacity (FITC–dextran uptake) of macrophages. The effects of LM49 were significantly inhibited by the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. In particular, LY294002 attenuated the phagocytic capacity of RAW264.7 cells induced by LM49 and prevented the effects on cytokines. Conclusion These findings suggest that LM49 possesses anti-inflammatory activity on LPS-stimulated RAW264.7 cells, in which the PI3K/Akt pathway plays an essential role. LM49 may have clinical utility as an anti-inflammatory agent. Graphic abstract In this study, we demonstrated that a halophenol derivative (LM49) could possess anti-inflammatory activity on LPS-stimulated RAW264.7 cells by reducing pro-inflammatory cytokines and enhancing the phagocytic capacity, in which the PI3K/Akt pathway plays an essential role. LM49 may have clinical utility as an anti-inflammatory agent.