Tags

Type your tag names separated by a space and hit enter

Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways.
Eur J Pharmacol. 2008 Feb 02; 580(1-2):70-9.EJ

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 kappaB (NF-kappaB) 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-kappaB through inhibiting phosphorylation at the activation loop of IkappaBalpha kinase beta, phosphorylation and degradation of IkappaBalpha, and NF-kappaB 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-kappaB and Akt activation and that both pathways in the osteoclast lineage are highly sensitive to berberine treatment.

Authors+Show Affiliations

Stomatological Hospital of Jilin University, Changchun 130041, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18083161

Citation

Hu, Jin-Ping, et al. "Berberine Inhibits RANKL-induced Osteoclast Formation and Survival Through Suppressing the NF-kappaB and Akt Pathways." European Journal of Pharmacology, vol. 580, no. 1-2, 2008, pp. 70-9.
Hu JP, Nishishita K, Sakai E, et al. Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways. Eur J Pharmacol. 2008;580(1-2):70-9.
Hu, J. P., Nishishita, K., Sakai, E., Yoshida, H., Kato, Y., Tsukuba, T., & Okamoto, K. (2008). Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways. European Journal of Pharmacology, 580(1-2), 70-9.
Hu JP, et al. Berberine Inhibits RANKL-induced Osteoclast Formation and Survival Through Suppressing the NF-kappaB and Akt Pathways. Eur J Pharmacol. 2008 Feb 2;580(1-2):70-9. PubMed PMID: 18083161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways. AU - Hu,Jin-Ping, AU - Nishishita,Kazuhisa, AU - Sakai,Eiko, AU - Yoshida,Hajime, AU - Kato,Yuzo, AU - Tsukuba,Takayuki, AU - Okamoto,Kuniaki, Y1 - 2007/11/17/ PY - 2007/07/30/received PY - 2007/10/25/revised PY - 2007/11/03/accepted PY - 2007/12/18/pubmed PY - 2008/5/2/medline PY - 2007/12/18/entrez SP - 70 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 580 IS - 1-2 N2 - 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 kappaB (NF-kappaB) 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-kappaB through inhibiting phosphorylation at the activation loop of IkappaBalpha kinase beta, phosphorylation and degradation of IkappaBalpha, and NF-kappaB 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-kappaB and Akt activation and that both pathways in the osteoclast lineage are highly sensitive to berberine treatment. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18083161/Berberine_inhibits_RANKL_induced_osteoclast_formation_and_survival_through_suppressing_the_NF_kappaB_and_Akt_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)01242-3 DB - PRIME DP - Unbound Medicine ER -