Inhibitory effects of 16-hydroxycleroda-3,13(14)E-dien-15-oic acid on superoxide anion and elastase release in human neutrophils through multiple mechanisms

Han Lin Chang, Fang Rong Chang, Jin Shan Chen, Hui Po Wang, Yi Hsiu Wu, Chien Chiao Wang, Yang Chang Wu, Tsong Long Hwang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Reactive oxygen species and granule proteases produced by neutrophils contribute to the pathogenesis of inflammatory diseases. In this study, a cellular model in isolated human neutrophils was established to elucidate the anti-inflammatory functions of 16-hydroxycleroda-3,13(14)E-dien-15-oic acid (PL3S), a clerodane diterpenoid from Formosan Polyalthia longifolia var. pendula. PL3S significantly inhibited the generation of superoxide anion and the release of elastase in formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP)-activated human neutrophils in a concentration-dependent fashion with IC50 values of 3.06 ± 0.20 and 3.30 ± 0.48 μM, respectively. PL3S did not affect cAMP-dependent pathway, and the inhibitory effect of PL3S was not reversed by protein kinase A inhibitor. PL3S did not display antioxidant or superoxide anion-scavenging ability, and it failed to alter the subcellular NADPH oxidase activity. PL3S concentration-dependently inhibited calcium mobilization caused by FMLP but not thapsigargin. Furthermore, PL3S attenuated the FMLP-induced protein kinase B (AKT) and p38 mitogen-activated protein kinase phosphorylation. However, PL3S had no effect on FMLP-induced phosphorylation of extracellular regulated kinase and c-Jun N-terminal kinase. In summary, these results indicate that the suppressive effects of PL3S on human neutrophil respiratory burst and degranulation are at least partly mediated by inhibition of calcium, AKT, and p38 signaling pathways.

Original languageEnglish
Pages (from-to)332-339
Number of pages8
JournalEuropean Journal of Pharmacology
Volume586
Issue number1-3
DOIs
Publication statusPublished - May 31 2008

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leucyl-phenylalanine
Pancreatic Elastase
Superoxides
Neutrophils
Acids
Polyalthia
Clerodane Diterpenes
Phosphorylation
Calcium
Proto-Oncogene Proteins c-akt
Thapsigargin
Respiratory Burst
JNK Mitogen-Activated Protein Kinases
Diterpenes
NADPH Oxidase
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Inhibitory Concentration 50
Reactive Oxygen Species

Keywords

  • Clerodane diterpenoid
  • Elastase
  • Neutrophil
  • Polyalthia longifolia
  • Superoxide anion

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Inhibitory effects of 16-hydroxycleroda-3,13(14)E-dien-15-oic acid on superoxide anion and elastase release in human neutrophils through multiple mechanisms. / Chang, Han Lin; Chang, Fang Rong; Chen, Jin Shan; Wang, Hui Po; Wu, Yi Hsiu; Wang, Chien Chiao; Wu, Yang Chang; Hwang, Tsong Long.

In: European Journal of Pharmacology, Vol. 586, No. 1-3, 31.05.2008, p. 332-339.

Research output: Contribution to journalArticle

Chang, Han Lin ; Chang, Fang Rong ; Chen, Jin Shan ; Wang, Hui Po ; Wu, Yi Hsiu ; Wang, Chien Chiao ; Wu, Yang Chang ; Hwang, Tsong Long. / Inhibitory effects of 16-hydroxycleroda-3,13(14)E-dien-15-oic acid on superoxide anion and elastase release in human neutrophils through multiple mechanisms. In: European Journal of Pharmacology. 2008 ; Vol. 586, No. 1-3. pp. 332-339.
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AU - Chang, Han Lin

AU - Chang, Fang Rong

AU - Chen, Jin Shan

AU - Wang, Hui Po

AU - Wu, Yi Hsiu

AU - Wang, Chien Chiao

AU - Wu, Yang Chang

AU - Hwang, Tsong Long

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N2 - Reactive oxygen species and granule proteases produced by neutrophils contribute to the pathogenesis of inflammatory diseases. In this study, a cellular model in isolated human neutrophils was established to elucidate the anti-inflammatory functions of 16-hydroxycleroda-3,13(14)E-dien-15-oic acid (PL3S), a clerodane diterpenoid from Formosan Polyalthia longifolia var. pendula. PL3S significantly inhibited the generation of superoxide anion and the release of elastase in formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP)-activated human neutrophils in a concentration-dependent fashion with IC50 values of 3.06 ± 0.20 and 3.30 ± 0.48 μM, respectively. PL3S did not affect cAMP-dependent pathway, and the inhibitory effect of PL3S was not reversed by protein kinase A inhibitor. PL3S did not display antioxidant or superoxide anion-scavenging ability, and it failed to alter the subcellular NADPH oxidase activity. PL3S concentration-dependently inhibited calcium mobilization caused by FMLP but not thapsigargin. Furthermore, PL3S attenuated the FMLP-induced protein kinase B (AKT) and p38 mitogen-activated protein kinase phosphorylation. However, PL3S had no effect on FMLP-induced phosphorylation of extracellular regulated kinase and c-Jun N-terminal kinase. In summary, these results indicate that the suppressive effects of PL3S on human neutrophil respiratory burst and degranulation are at least partly mediated by inhibition of calcium, AKT, and p38 signaling pathways.

AB - Reactive oxygen species and granule proteases produced by neutrophils contribute to the pathogenesis of inflammatory diseases. In this study, a cellular model in isolated human neutrophils was established to elucidate the anti-inflammatory functions of 16-hydroxycleroda-3,13(14)E-dien-15-oic acid (PL3S), a clerodane diterpenoid from Formosan Polyalthia longifolia var. pendula. PL3S significantly inhibited the generation of superoxide anion and the release of elastase in formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP)-activated human neutrophils in a concentration-dependent fashion with IC50 values of 3.06 ± 0.20 and 3.30 ± 0.48 μM, respectively. PL3S did not affect cAMP-dependent pathway, and the inhibitory effect of PL3S was not reversed by protein kinase A inhibitor. PL3S did not display antioxidant or superoxide anion-scavenging ability, and it failed to alter the subcellular NADPH oxidase activity. PL3S concentration-dependently inhibited calcium mobilization caused by FMLP but not thapsigargin. Furthermore, PL3S attenuated the FMLP-induced protein kinase B (AKT) and p38 mitogen-activated protein kinase phosphorylation. However, PL3S had no effect on FMLP-induced phosphorylation of extracellular regulated kinase and c-Jun N-terminal kinase. In summary, these results indicate that the suppressive effects of PL3S on human neutrophil respiratory burst and degranulation are at least partly mediated by inhibition of calcium, AKT, and p38 signaling pathways.

KW - Clerodane diterpenoid

KW - Elastase

KW - Neutrophil

KW - Polyalthia longifolia

KW - Superoxide anion

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