Bisbenzylisoquinoline alkaloids of lotus (Nelumbo nucifera Gaertn.) seed embryo inhibit lipopolysaccharide-induced macrophage activation via suppression of Ca2+-CaM/CaMKII pathway

ABSTRACT Macrophage hyperactivation is associated with various inflammatory diseases. In this study, the effects of nine bisbenzylisoquinoline alkaloids on NO production by LPS-activated RAW264.7 macrophages were evaluated. It was found that certain bisbenzylisoquinoline alkaloids with single oxygen bridge have more potent effects than those with two oxygen bridges. Further studies revealed that three bisbenzylisoquinoline alkaloids (Neferine, Liensinine and Isoliensinine) of lotus (Nelumbo nucifera Gaertn.) seed embryo, a homology of traditional Chinese medicine and food, can also reduce LPS-induced expression of iNOS and production of IL-1β, IL-6 and TNF-α by blocking IκBα phosphorylation and degradation. And this effect is mediated at least partly by the inhibition of cytosolic Ca2+ level and CaM expression as well as the binding of three alkaloids with CaM, thereby inhibiting the subsequent phosphorylation of CaMKII. These results revealed for the first time that three bisbenzylisoquinoline alkaloids of lotus embryo play an anti-inflammatory role via suppressing Ca2+-CaM/CaMKII pathway