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. 2018 Jan 5;16(1):14.
doi: 10.3390/md16010014.

Suppression of RANKL-Induced Osteoclastogenesis by the Metabolites from the Marine Fungus Aspergillus flocculosus Isolated from a Sponge Stylissa sp

Affiliations

Suppression of RANKL-Induced Osteoclastogenesis by the Metabolites from the Marine Fungus Aspergillus flocculosus Isolated from a Sponge Stylissa sp

Hee Jae Shin et al. Mar Drugs. .

Abstract

A new α-pyrone merosesquiterpenoid possessing an angular tetracyclic carbon skeleton, ochraceopone F (1), and four known secondary metabolites, aspertetranone D (2), cycloechinulin (3), wasabidienone E (4), and mactanamide (5), were isolated from the marine fungus Aspergillus flocculosus derived from a sponge Stylissa sp. collected in Vietnam. The structures of Compounds 1-5 were elucidated by analysis of 1D and 2D NMR spectra and MS data. All the isolated compounds were evaluated for anti-proliferation activity and their suppression effects on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation using tartate-resisant acid phosphatase (TRAP). Compounds 1-5 had no anti-proliferative effect on human cancer cell lines up to 30 μg/mL. Among these compounds, aspertetranone D (2) and wasabidienone E (4) exhibited weak osteoclast differentiation inhibitory activity at 10 μg/mL. However, mactanamide (5) showed a potent suppression effect of osteoclast differentiation without any evidence of cytotoxicity.

Keywords: Aspergillus flocculosus; TRAP assay; mactanamide; marine fungus; osteoclastogenesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of Compounds 15 isolated from Aspergillus flocculosus.
Figure 2
Figure 2
Key 1H-1H COSY, HMBC, and ROESY correlations of ochraceopone F (1).
Figure 3
Figure 3
(A) Cell viability was measured by XTT assay. (B) Bone marrow macrophages (BMMs) were treated with vehicle or indicated concentration of Compounds 15 in the presence of RANKL and M-CSF. Cells were fixed with 10% formalin, stained by chromogenic substrate dissolved in tartate-containing buffer, and photographed under a light microscopy.
Figure 3
Figure 3
(A) Cell viability was measured by XTT assay. (B) Bone marrow macrophages (BMMs) were treated with vehicle or indicated concentration of Compounds 15 in the presence of RANKL and M-CSF. Cells were fixed with 10% formalin, stained by chromogenic substrate dissolved in tartate-containing buffer, and photographed under a light microscopy.
Figure 4
Figure 4
(A) Supernatants were mixed with chromogenic substrate dissolved in tartrate-containing buffer and TRAP activity was determined by measuring optical density at 540 nm. Each column shows the mean ± S.D. of quadruplicate determinations. Statistical significance was analyzed by one-way ANOVA and Dunnett’s t-test (* p < 0.05). (B) Cells were fixed with 10% formalin and stained by chromogenic substrate containing TRAP.

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