Diaporisoindole E inhibits RANKL-induced osteoclastogenesis via suppression of PI3K/AKT and MAPK signal pathways

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
Pei HuaQiong Gu

Abstract

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. The purpose of this study is to investigate the inhibitory effect of SA8 in RANKL-induced osteoclastogenesis and to explore its mechanism of action. 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. 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 hydroxyap...Continue Reading

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