Diaporisoindole E inhibits RANKL-induced osteoclastogenesis via suppression of PI3K/AKT and MAPK signal pathways.
Phytomedicine
; 75: 153234, 2020 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-32510335
ABSTRACT
BACKGROUND:
Diaporisoindole E (SA8), an isoprenylisoindole alkaloids isolated from the mangrove endophytic fungus Diaporthe sp. SYSU-HQ3, was reported with anti-inflammatory activity in RAW264.7 cells. However, the effect of SA8 in bone metabolism is unknown.PURPOSE:
The purpose of this study is to investigate the inhibitory effect of SA8 in RANKL-induced osteoclastogenesis and to explore its mechanism of action.METHODS:
Osteoclastogenesis was assayed by TRAP staining. Expression of osteoclast specific genes was evaluated by real time-PCR. The inhibition of phosphorylation of the protein was measured by western blot analysis. The transcription activity of NF-κB was conducted using luciferase reporter gene assays. Osteoblast differentiation was assayed by alkaline phosphatase and Alizarin Red staining.RESULTS:
SA8 significantly inhibited the osteoclast differentiation in a dose- and time-dependent manner, which is consistent with the suppression of osteoclast specific genes including TRAP, DC-stamp, NFATc1, MMP-9, and ATP6v0d2. Further study on the mechanism of action revealed that SA8 inhibited osteoclast differentiation by attenuating PI3K/AKT and MAPK but not through NF-κB signaling pathways. Moreover, SA8 also suppressed bone resorption activity in a hydroxyapatite-coated plate without affecting osteoblast differentiation in C3H10T1/2 using alkaline phosphatase and Alizarin Red staining.CONCLUSIONS:
These findings suggest that SA8 (Diaporisoindole E) is the potential anti-osteoporosis agent.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
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Osteogênese
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Fosfatidilinositol 3-Quinases
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Alcaloides Indólicos
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Proteínas Proto-Oncogênicas c-akt
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Ligante RANK
Idioma:
En
Revista:
Phytomedicine
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China