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Human Neutrophil Elastase Inhibitory Alkaloids from Chelidonium majus L.

  • Kim, Jeong Yoon (Division of Applied Life Science (BK21 plus), IALS, Graduate School of Gyeongsang National University) ;
  • Lee, Ji Hye (Division of Applied Life Science (BK21 plus), IALS, Graduate School of Gyeongsang National University) ;
  • Song, Yeong Hun (Division of Applied Life Science (BK21 plus), IALS, Graduate School of Gyeongsang National University) ;
  • Jeong, Won Min (Division of Applied Life Science (BK21 plus), IALS, Graduate School of Gyeongsang National University) ;
  • Tan, Xuefei (Division of Applied Life Science (BK21 plus), IALS, Graduate School of Gyeongsang National University) ;
  • Uddin, Zia (Division of Applied Life Science (BK21 plus), IALS, Graduate School of Gyeongsang National University) ;
  • Park, Ki Hun (Division of Applied Life Science (BK21 plus), IALS, Graduate School of Gyeongsang National University)
  • Received : 2015.07.12
  • Accepted : 2015.08.04
  • Published : 2015.09.30

Abstract

Human neutrophil elastase (HNE) represents a good therapeutic target for the treatment of inflammatory diseases as well as invasion of microorganism. The methanol extract of a aerial part of Chelidonium majus L. showed high activity against the neutrophil elastase with an $IC_{50}$ value of $100{\mu}g/mL$. Due to its potency, subsequent bioactivity-guided fractionation of methanol extract led to six alkaloids (1-6), which were identified as dihydrosanguinarine (1), (s)-stylopine (2), arnottianamide (3), (+)-chelidonine (4), spallidamine (5), and N-trans-feruloyltyramine (6). Among of them, three alkaloids (2, 5, and 6) inhibited HNE in a dose-dependent manner with $IC_{50}$ ranging between 11.6 and $51.0{\mu}M$. Lineweaver-Burk and Dixon plots, and their secondary replots showed that alkaloids (2, 5, and 6) were mixed inhibitors of HNE. The analysis of $K_I$ and $K_{IS}$ value proved that all inhibitors (2, 5, and 6) had reversible mixed type I mechanism.

Keywords

References

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