Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-κB and Akt pathways

Jin Ping Hu, Kazuhisa Nishishita, Eiko Sakai, Hajime Yoshida, Yuzo Kato, Takayuki Tsukuba, Kuniaki Okamoto

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Berberine, an isoquinoline alkaloid isolated from several medicinal plants, has been reported to possess anti-bacterial, anti-inflammatory and antitumor properties. Although berberine also inhibits osteoclastogenesis and bone resorption, the molecular machinery for its inhibitory effects remains unknown. This study focused on the suppressive effects of berberine on receptor activator of nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis and survival. Berberine inhibited RANKL-mediated osteoclast formation and survival while having no cytotoxic effects on bone marrow macrophages or osteoblastic cells. Berberine attenuated RANKL-induced activation of NF-κB through inhibiting phosphorylation at the activation loop of IκBα kinase β, phosphorylation and degradation of IκBα, and NF-κB p65 nuclear translocation. RANKL-induced Akt phosphorylation was strongly inhibited by berberine; however, neither monocyte/macrophage-colony stimulating factor (M-CSF)-induced nor insulin-induced Akt activation was inhibited by the drug. Under M-CSF- and RANKL-deprived condition, berberine increased the active form of caspase-3 in osteoclasts. By contrast, berberine did not potentiate the activation of caspase-3 in M-CSF-deprived bone marrow macrophages. These findings indicate that berberine inhibits osteoclast formation and survival through suppression of NF-κB and Akt activation and that both pathways in the osteoclast lineage are highly sensitive to berberine treatment.

Original languageEnglish
Pages (from-to)70-79
Number of pages10
JournalEuropean Journal of Pharmacology
Volume580
Issue number1-2
DOIs
Publication statusPublished - Feb 2 2008
Externally publishedYes

Fingerprint

Berberine
Osteoclasts
Macrophage Colony-Stimulating Factor
Phosphorylation
Osteogenesis
Caspase 3
Berberine Alkaloids
Bone Marrow
Macrophages
Medicinal Plants
Bone Resorption
Cytoplasmic and Nuclear Receptors
Monocytes
Anti-Inflammatory Agents
Phosphotransferases
Insulin
Ligands

Keywords

  • Akt
  • Apoptosis
  • Berberine
  • NF-κB
  • Osteoclast
  • RANKL

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-κB and Akt pathways. / Hu, Jin Ping; Nishishita, Kazuhisa; Sakai, Eiko; Yoshida, Hajime; Kato, Yuzo; Tsukuba, Takayuki; Okamoto, Kuniaki.

In: European Journal of Pharmacology, Vol. 580, No. 1-2, 02.02.2008, p. 70-79.

Research output: Contribution to journalArticle

Hu, Jin Ping ; Nishishita, Kazuhisa ; Sakai, Eiko ; Yoshida, Hajime ; Kato, Yuzo ; Tsukuba, Takayuki ; Okamoto, Kuniaki. / Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-κB and Akt pathways. In: European Journal of Pharmacology. 2008 ; Vol. 580, No. 1-2. pp. 70-79.
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