Harmine, a β-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo

Yonezawa, Takayuki; Hasegawa, Shinichi; Asai, Midori; Ninomiya, Tadashi; Sasaki, Toshinori; Cha, Byung‐Yoon; Teruya, Toshiaki; Ozawa, Hiroki; Yagasaki, Kazumi; Nagai, Kazuo; Woo, Je‐Tae

doi:10.1016/j.ejphar.2010.10.048

Cited by 53 publications

(39 citation statements)

References 25 publications

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“…Furthermore, harmine prevented RANKLinduced bone resorption in both cell and bone tissue cultures [3] .…”

Section: Effect Of Harmine On Bone Systemmentioning

confidence: 99%

“…Neurochemical and behavioral studies have shown that some beta-carboline alkaloids facilitate the dopaminergic transmission and interact with D1 and D2 dopaminergic receptors in the striatum [8] . Most beta-carboline alkaloids are known to be strong inhibitors of which metabolizes catecholamine neurotransmitters [3] . Harmine possesses antidepressant activity by interacting with MAO A and several cell-surface receptors, including serotonin receptor 2A (5-hydroxytrytamine receptor 2A, 5-HT2A) [12] .…”

Section: Overview Of Alkaloidsmentioning

confidence: 99%

“…Harmine is widely distributed in nature, such as in various plants, marine creatures, insects, mammalians, human tissues and body fluids. Harmine have antimicrobial, antiplasmodial, antifungal, antioxidative, antitumor, antimutagenic, cytotoxic and hallucinogenic properties [1][2][3][4][5][6][7] . Beta-carboline compounds act as inverse agonists at the benzodiazepine site of the gammaaminobutyric acid type A receptors and have actions entirely opposite to those of the anxiolytic benzodiazepines.…”

Section: Introductionmentioning

confidence: 99%

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A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

Patel

Gadewar

Tripathi

et al. 2012

Asian Pacific Journal of Tropical Biomedicine

216

120

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“…Furthermore, harmine prevented RANKLinduced bone resorption in both cell and bone tissue cultures [3] .…”

Section: Effect Of Harmine On Bone Systemmentioning

confidence: 99%

Section: Overview Of Alkaloidsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

Patel

Gadewar

Tripathi

et al. 2012

Asian Pacific Journal of Tropical Biomedicine

216

120

View full text Add to dashboard Cite

“…Some natural compounds have also been shown to inhibit osteoclast differentiation. 3,4) However, many patients have already lost bone mass before any receiving any treatment. Bone formation therefore needs to be accelerated to treat osteoporosis.…”

mentioning

confidence: 99%

APrunus mumeExtract Stimulated the Proliferation and Differentiation of Osteoblastic MC3T3-E1 Cells

Kono

Okuno

Inada

et al. 2011

Bioscience, Biotechnology, and Biochemistry

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Osteoporosis is a serious disease caused by decreased bone mass. There is constant matrix remodeling in bones, by which bone formation is performed by osteoblastic cells, whereas bone resorption is accomplished by osteoclast cells. We investigated the effect of a Japanese apricot (Prunus mume SIBE. et ZUCC.) extract on the proliferation and osteoblastic differentiation in pre-osteoblastic MC3T3-E1 cells. An alkaline phosphatase (ALP) activity assay, cell proliferation assay, alizarin red staining and expression analysis of osteoblastic genes were carried out to assess the proliferation and osteoblastic differentiation. The water-soluble fraction of Prunus mume (PWF) increased the ALP activity, cell proliferation and mineralization. The gene expression of osteopontin and bone morphogenetic protein-2, which are markers in the early period of osteoblastic differentiation, were significantly enhanced by the PWF treatment. PWF therefore stimulated the proliferation and osteoblastic differentiation of cells and may have potential to prevent osteoporosis.

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“…RANKL-induced osteoclastogenesis is mediated by M-CSF and RANKL. RANKL predominantly activates AKT, ERK, NF-kB and AP-1 signaling pathways [27][28][29]. MAPKNFATc1 constitutes the main downstream signaling cascade of RANKL during early-stage osteoclastogenesis (within 24h from RANKL-stimulation), whilst TRACP and cathepsin K are required for bone resorption during late-stage osteoclastogenesis (>48h from RANKLstimulation).…”

Section: Discussionmentioning

confidence: 99%

Psoralen and Bakuchiol Ameliorate M-CSF Plus RANKL-Induced Osteoclast Differentiation and Bone Resorption Via Inhibition of AKT and AP-1 Pathways in Vitro

Chai

Zhou

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Psoralen and bakuchiol are the main active compounds found in the traditional Chinese medicine Psoralea corylifolia L., and have been used to treat osteoporosis. This study aims to investigate the anti-osteoporosis effects of these two compounds using osteoclasts precursor differentiation and bone absorption assays in vitro. Methods: Primary mouse osteoclasts precursor cells were induced by M-CSF (macrophage colony stimulating factor) plus RANKL (receptor activator of nuclear factor kappa-B ligand) in vitro. TRACP (tartrate-resistant acid phosphatase) enzyme activity and toluidine blue staining were used to observe the effects of psoralen and bakuchiol on osteoclast differentiation and bone resorption, respectively. Gelatin zymography was used to assess MMP (matrix metalloproteinase) activity, and ELISA was performed to measure cathepsin K activity. Western blotting analysis for expression of phosphorylated AKT, ERK, NF-kB, and c-jun; and immunofluorescence analysis for c-jun and p65 nuclear translocation in induced osteoclasts were then used to determine the mechanism of anti-bone resorption of psoralen and bakuchiol. Results: Mature osteoclasts were induced by M-CSF plus RANKL from primary bone marrow macrophages in vitro. Both psoralen and bakuchiol significantly inhibited TRACP enzyme activity and slightly decreased the number of TRACP⁺ multinuclear osteoclasts induced by M-CSF plus RANKL. Bakuchiol significantly decreased bone lacunae area and attenuated MMP-2 activity induced by M-CSF plus RANKL in osteoclasts. Both psoralen and bakuchiol significantly decreased the expression and nuclear translocation of phosphorylated c-jun stimulated by M-CSF plus RANKL, but no significant effect on p65 translocation was observed in osteoclasts. Additionally, bakuchiol significantly attenuated the increased of M-CSF plus RANKL-induced phosphorylation of AKT in osteoclasts. Conclusions: Psoralen and bakuchiol ameliorated M-CSF plus RANKL-induced osteoclast differentiation and bone resorption via inhibition of AKT and AP-1 pathways activation in vitro.

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Harmine, a β-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo

Cited by 53 publications

References 25 publications

A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

APrunus mumeExtract Stimulated the Proliferation and Differentiation of Osteoblastic MC3T3-E1 Cells

Psoralen and Bakuchiol Ameliorate M-CSF Plus RANKL-Induced Osteoclast Differentiation and Bone Resorption Via Inhibition of AKT and AP-1 Pathways in Vitro

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