Isolation and characterization of sesquiterpenes from Arecophila saccharicola YMJ96022401 with NO production inhibitory activity.
Sesquiterpenes, arecoic acids A-F and arecolactone, were isolated from the ethyl acetate extracts of the fermented broth of Arecophila saccharicola YMJ96022401 along with two known analogues 1,7α,10α-trihydroxyeremophil-11(13)-en-12,8-olide and 1,10α,13-trihydroxyeremophil-7(11)-en-12,8-olide. Their structures were elucidated on the basis of spectroscopic data analyses. The inhibitory effects of all of these compounds on nitric oxide (NO) production in lipopolysaccharide (LPS, 200 μg/mL)-activated murine macrophage RAW264.7 cells were also evaluated. Among these compounds, 1,7α,10α-trihydroxyeremophil-11(13)-en-12,8-olide significantly inhibited NO production without any cytotoxicity, and its average maximum inhibition (E(max)) at 100 μM and median inhibitory concentration (IC₅₀) were 85.7%±0.8% and 16.5±1.0 μM, respectively. Arecolactone was the most potent, with the E(max) at 12.5 μM and IC₅₀ being 94.7%±0.8% and 1.32±0.1 μM, respectively, but displayed cytotoxicity at considerable higher concentrations than 25 μM. Analyses of Western blotting indicated that arecolactone (0.8-12.5 μM) inhibited induction of inducible NO synthase (iNOS) by LPS, which involved suppression of NF-κB activation and the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH₂-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) in activated RAW 264.7 cells. In addition, arecolactone concentration-dependently prevented the vascular hyporeactivity to phenylephrine induced by LPS (300 ng/mL) through iNOS pathway in isolated rat thoracic aortic rings. These results indicated that both of these naturally occurring iNOS inhibitors may provide a rationale for the potential anti-inflammatory effect of A. saccharicola YMJ96022401.
Department of Microbiology and Immunology, Taipei Medical University, Taipei 110, Taiwan.
Lin-Wen
LW
Lee
Guei-Jane
GJ
Wang
Mei-Hsiang
MH
Lin
Yu-Min
YM
Ju
Yen-Wen
YW
Lin
Fang-Yu
FY
Chen
Tzong-Huei
TH
Lee
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D012717:Sesquiterpenes; D009569:Nitric Oxide; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases