Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways

Abstract

Background/Aims: This study aimed to investigate the anti-inflammatory activity of Berbamine (BER), a bisbenzylisoquinoline alkaloid extracted from Berberis amurensis (Xiao Bo An), and the underlying mechanisms. Methods: Macrophages and neutrophils were treated with BER in vitro and stimulated with LPS and fMLP. The effects of BER on the expression of pro-inflammatory mediators in macrophages were evaluated with quantitative RT-PCR and ELISA. The effects of BER on the activation and superoxide release of neutrophils were determined with flow cytometry and WST-1 reduction test. The inhibitory effects of BER on the activation of signaling pathways related to inflammatory response in macrophages were evaluated by western blot analysis. In addition, a mouse peritonitis model was made by peritoneal injection of thioglycollate medium and anti-inflammatory effects of BER were investigated in vivo by quantitative analysis of pro-inflammatory factor production and leukocyte exudation. Results: BER significantly inhibited inflammatory factor expression by LPS-stimulated macrophages and suppressed activation and superoxide release of fMLP-stimulated neutrophils. In the mouse peritonitis model, BER significantly inhibited the activation of macrophages and exudation of neutrophils. According to analysis, BER significantly suppressed phosphorylation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways in LPS-stimulated macrophages. Conclusions: Collectively, data from this study suggest that BER has anti-inflammatory potential, which is effected via inhibition of NF-κB and MAPK signaling pathways, and thus holds promise for treatment of inflammatory disease.

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Bisbenzylisoquinoline alkaloids of lotus ( Nelumbo nucifera Gaertn.) seed embryo inhibit lipopolysaccharide-induced macrophage activation via suppression of Ca 2+ -CaM/CaMKII pathway

“…About 500 natural products belong to this large alkaloid class (Weber & Opatz, 2019). Lots of bisbenzylisoquinoline alkaloids, such as Neferine, Tetrandrine, Cepharanthine, Berbamine and Dauricine, have been found to inhibit the activation of macrophages and thus have anti-inflammatory activity (Gao, Feng, Zhang, Wang, & Cui, 2016;Jia et al, 2017;Paudel, Karki, & Kim, 2016;Qiao et al, 2019;Wu, Guo, Min, Pei, & Chen, 2018). However, the structure-activity relationship of these compounds is still unclear.…”