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Open Access Research article

Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis

Letizia Penolazzi1, Ilaria Lampronti1, Monica Borgatti1, Mahmud Tareq Hassan Khan23, Margherita Zennaro1, Roberta Piva1 and Roberto Gambari14*

Author Affiliations

1 BioPharmaNet, ER-GenTech, Department of Biochemistry and Molecular Biology, Ferrara University, Ferrara, Italy

2 Department of Pharmacology, Institute of Medical Biology, University of Tromso, Tromso, Norway

3 H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi, Pakistan

4 Biotechnology Center, Ferrara University, Ferrara, Italy

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BMC Complementary and Alternative Medicine 2008, 8:59  doi:10.1186/1472-6882-8-59

Published: 30 October 2008

Abstract

Background

Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of Emblica officinalis fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.

Methods

The effects of extracts from Emblica officinalis on differentiation and survival of human primary OCs cultures obtained from peripheral blood were determined by tartrate-acid resistant acid phosphatase (TRAP)-positivity and colorimetric MTT assay. The effects of Emblica officinalis extracts on induction of OCs apoptosis were studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally, in vitro effects of Emblica officinalis extracts on NF-kB transcription factor activity were determined by gel shift experiments.

Results

Extracts of Emblica officinalis were able to induce programmed cell death of mature OCs, without altering, at the concentrations employed in our study, the process of osteoclastogenesis. Emblica officinalis increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments demonstrated that Emblica officinalis extracts act by interfering with NF-kB activity, a transcription factor involved in osteoclast biology. The data obtained demonstrate that Emblica officinalis extracts selectively compete with the binding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observed effects of Emblica officinalis on the expression levels of interleukin-6, a NF-kB specific target gene.

Conclusion

Induction of apoptosis of osteoclasts could be an important strategy both in interfering with rheumatoid arthritis complications of the bone skeleton leading to joint destruction, and preventing and reducing osteoporosis. Accordingly, we suggest the application of Emblica officinalis extracts as an alternative tool for therapy applied to bone diseases.