| Summary: | 碩士 === 長庚大學 === 中醫學系天然藥物 === 99 === Neutrophils are phagocytic cells of the innate immune system that play a crucial role in host defence and inflammatory responses. It is well known that high concentrations of reactive oxygen species and granule proteases produced by activated neutrophils contribute to the pathogenesis of inflammatory diseases. Chalcone is abundantly present in the plant kingdom and has various biological activities such as anti-inflammatory and antioxidant. Herein, the anti-inflammatory effect of MVBR-28, a Mannich base of heterocyclic chalcone, and its underlying mechanisms were investigated in human neutrophils. Our data showed that MVBR-28 has potent inhibitory effects on superoxide anion generation, reactive oxygen species production, elastase release, and CD11b expression in N-formyl-methionyl-leucyl
-phenylalanine (FMLP)-induced human neutrophils. However, MVBR-28 displayed no abilities in the reduction of radical generation, superoxide anion production, and elastase activity in cell-free systems, and it failed to alter subcellular NADPH oxidase activity. MVBR-28 did not affect cellular cAMP concentrations, and the inhibitory effects of MVBR-28 were not reversed by inhibitors of protein kinase A and protein phosphatase. MVBR-28 only caused a slight decrease of FMLP-induced phosphorylations of ERK, JNK, p38 MAPK, and Akt. Significantly, MVBR-28 showed potent inhibition on Ca2+ mobilization in FMLP- and thapsigargin-activated human neutrophils. Furthermore, FMLP-induced intracellular alkalinization was reduction by MVBR-28, which was independent of intracellular Ca2+ concentration. In summary, the present study shows that MVBR-28 inhibits human neutrophil proinflammatory responses, including respiratory burst, degranulation, and adhesion. These anti-inflammatory effects are attributed to the intracellular acidification and inhibition of calcium entry. Our data suggest that MVBR-28 might have future potential to be developed as a novel anti-inflammatory agent for improving neutrophilic inflammatory diseases.
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