Structure and functions of gamma-dodecalactone isolated from Antrodia camphorata for NK cell activation
Resource
BIOORGANIC & MEDICINAL CHEMISTRY, 18(18), 6896-6804
Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Journal Volume
18
Journal Issue
18
Pages
6896-6804
Date Issued
2010
Date
2010
Author(s)
Chen, Chia-Jung
Krishna, R.Vijaya
Tsai, Chia-Che
Wu, Wan-Hsun
Chao, Louis Kuoping
Hwang, Kent-Hao
Chien, Chichen Michael
Chang, Hwan-You
Chen, Shui-Tein
Abstract
The preserved fungal species Antrodia camphorata has diverse health-promoting effects and has been popularly used in East Asia as a traditional herb. We isolated a volatile compound from the culture medium of A. camphorata and identified it as γ-dodecalactone (γ-DDL). Cytomic screening for immune-modulating activity revealed that γ-DDL can activate human NK cells to express the early activation marker CD69. Further experiments showed that γ-DDL not only can induce NK cells to express CD69 but also stimulate NK cells to secrete cytotoxic molecules (FasL and granzyme B) and Th1 cytokines (TNF-α and INF-γ). Measuring the distribution of γ-DDL in the subcellular compartments of NK cells revealed that γ-DDL has been converted to 4-hydroxydodecanoic acid (an acyclic isomer of γ-DDL) in a time-dependent manner in the cytoplasm. Synthetic (R,S)-4-hydroxydodecanoic acid activated NK cells to express CD69 mRNA within 10 min, in contrast to γ-DDL, which activated NK cells to express CD69 within 50 min. This faster activation suggests that γ-DDL has converted to 4-hydroxydodecanoic acid and to stimulate the NK cells to express CD69. Optically pure (R)-(+)-4-hydroxydodecanoic acid and (S)-(-)-4-hydroxydodecanoic acid were obtained via: (1) synthesis of its diastereomeric esters of (R,S)-4-hydroxydodecanoic (R)-(-)-2-phenylpropionate; (2) separation of diastereomers via preparative HPLC, and (3) subsequent hydrolysis of the obtained optical pure ester of (R)-(+)-4-hydroxydodecanoic acid (R)-(-)-2-phenylpropionate and (R)-(-)-4-hydroxydodecanoic acid (R)-(-)-2-phenylpropionate, respectively. Further assays of NK cells activation using each enantiomer showed that only the (R)-(+)-4-hydroxydodecanoic acid can activate NK cells. ? 2010 Elsevier Ltd. All rights reserved.
Subjects
γ-Dodecalactone; 4-Hydroxydodecanoic acid; Antrodia camphorata; CD69; NK cells
SDGs
Other Subjects
2 phenylpropionate; 4 hydroxydodecanoic acid; CD69 antigen; Fas ligand; fungal protein; gamma dodecalactone; gamma interferon; granzyme B; immunomodulating agent; tumor necrosis factor alpha; unclassified drug; Antrodia camphorata; article; cell activation; cell compartmentalization; concentration response; controlled study; cytoplasm; cytotoxicity; diastereoisomer; drug identification; drug isolation; enantiomer; fungus culture; high performance liquid chromatography; human; human tissue; hydrolysis; natural killer cell; protein expression; structure activity relation; 4-Butyrolactone; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Antrodia; Fas Ligand Protein; Granzymes; Humans; Interferon-gamma; Killer Cells, Natural; Lectins, C-Type; Lymphocyte Activation; Stereoisomerism; Tumor Necrosis Factor-alpha; Taiwanofungus camphoratus
Type
journal article
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