Sanguiin H-6, a constituent of Rubus parvifolius L., inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorption in vitro and prevents tumor necrosis factor-α-induced osteoclast formation in vivo

Eiko Sakai, Yuri Aoki, Masako Yoshimatsu, Kazuhisa Nishishita, Mayumi Iwatake, Yutaka Fukuma, Kuniaki Okamoto, Takashi Tanaka, Takayuki Tsukuba

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background Osteoclasts are multinucleated bone-resorbing cells that differentiate in response to receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). Enhanced osteoclastogenesis contributes to bone diseases, such as osteoporosis and rheumatoid arthritis. Rubus parvifolius L. is traditionally used as an herbal medicine for rheumatism; however, its detailed chemical composition and the molecular mechanisms responsible for its biological action have not been elucidated. Purpose To investigate the mechanisms by which R. parvifolius L. extract and its major constituent sanguiin H-6, inhibit osteoclastogenesis and bone resorption. Methods Cell proliferation, cell differentiation, and bone resorption were detected in vitro. Inhibition of signaling pathways, marker protein expression, and protein nuclear translocation were evaluated by western blot analysis. Tumor necrosis factor-α (TNF-α)-mediated osteoclastogenesis was examined in vivo. Results R. parvifolius L. extract inhibited the bone-resorption activity of osteoclasts. In addition, sanguiin H-6 markedly inhibited RANKL-induced osteoclast differentiation and bone resorption, reduced reactive oxygen species production, and inhibited the phosphorylation of inhibitor of NF-κB alpha (IκBα) and p38 mitogen-activated protein kinase. Sanguiin H-6 also decreased the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), cathepsin K, and c-Src. Moreover, sanguiin H-6 inhibited the nuclear translocation of NFATc1, c-Fos, and NF-κB in vitro, as well as TNF-α-mediated osteoclastogenesis in vivo. Conclusions Our data revealed that R. parvifolius L. has anti-bone resorption activity and suggest that its constituent, sanguiin H-6, can potentially be used for the prevention and treatment of bone diseases associated with excessive osteoclast formation and subsequent bone destruction.

Original languageEnglish
Pages (from-to)828-837
Number of pages10
JournalPhytomedicine
Volume23
Issue number8
DOIs
Publication statusPublished - Jul 15 2016
Externally publishedYes

Fingerprint

Osteoclasts
Bone Resorption
Cytoplasmic and Nuclear Receptors
Osteogenesis
Tumor Necrosis Factor-alpha
Ligands
NFATC Transcription Factors
Bone Diseases
Cathepsin K
Herbal Medicine
p38 Mitogen-Activated Protein Kinases
Protein Transport
Rheumatic Diseases
Osteoporosis
Cell Differentiation
Reactive Oxygen Species
Rheumatoid Arthritis
Western Blotting
Phosphorylation
Cell Proliferation

Keywords

  • c-Fos
  • Nuclear factor of activated T cells cytoplasmic-1
  • Osteoclast
  • Receptor activator of nuclear factor-κb
  • Sanguiin H-6

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

Cite this

Sanguiin H-6, a constituent of Rubus parvifolius L., inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorption in vitro and prevents tumor necrosis factor-α-induced osteoclast formation in vivo. / Sakai, Eiko; Aoki, Yuri; Yoshimatsu, Masako; Nishishita, Kazuhisa; Iwatake, Mayumi; Fukuma, Yutaka; Okamoto, Kuniaki; Tanaka, Takashi; Tsukuba, Takayuki.

In: Phytomedicine, Vol. 23, No. 8, 15.07.2016, p. 828-837.

Research output: Contribution to journalArticle

Sakai, Eiko ; Aoki, Yuri ; Yoshimatsu, Masako ; Nishishita, Kazuhisa ; Iwatake, Mayumi ; Fukuma, Yutaka ; Okamoto, Kuniaki ; Tanaka, Takashi ; Tsukuba, Takayuki. / Sanguiin H-6, a constituent of Rubus parvifolius L., inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorption in vitro and prevents tumor necrosis factor-α-induced osteoclast formation in vivo. In: Phytomedicine. 2016 ; Vol. 23, No. 8. pp. 828-837.
@article{4226bd2b9dc842eb99356df9e7b4d8e2,
title = "Sanguiin H-6, a constituent of Rubus parvifolius L., inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorption in vitro and prevents tumor necrosis factor-α-induced osteoclast formation in vivo",
abstract = "Background Osteoclasts are multinucleated bone-resorbing cells that differentiate in response to receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). Enhanced osteoclastogenesis contributes to bone diseases, such as osteoporosis and rheumatoid arthritis. Rubus parvifolius L. is traditionally used as an herbal medicine for rheumatism; however, its detailed chemical composition and the molecular mechanisms responsible for its biological action have not been elucidated. Purpose To investigate the mechanisms by which R. parvifolius L. extract and its major constituent sanguiin H-6, inhibit osteoclastogenesis and bone resorption. Methods Cell proliferation, cell differentiation, and bone resorption were detected in vitro. Inhibition of signaling pathways, marker protein expression, and protein nuclear translocation were evaluated by western blot analysis. Tumor necrosis factor-α (TNF-α)-mediated osteoclastogenesis was examined in vivo. Results R. parvifolius L. extract inhibited the bone-resorption activity of osteoclasts. In addition, sanguiin H-6 markedly inhibited RANKL-induced osteoclast differentiation and bone resorption, reduced reactive oxygen species production, and inhibited the phosphorylation of inhibitor of NF-κB alpha (IκBα) and p38 mitogen-activated protein kinase. Sanguiin H-6 also decreased the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), cathepsin K, and c-Src. Moreover, sanguiin H-6 inhibited the nuclear translocation of NFATc1, c-Fos, and NF-κB in vitro, as well as TNF-α-mediated osteoclastogenesis in vivo. Conclusions Our data revealed that R. parvifolius L. has anti-bone resorption activity and suggest that its constituent, sanguiin H-6, can potentially be used for the prevention and treatment of bone diseases associated with excessive osteoclast formation and subsequent bone destruction.",
keywords = "c-Fos, Nuclear factor of activated T cells cytoplasmic-1, Osteoclast, Receptor activator of nuclear factor-κb, Sanguiin H-6",
author = "Eiko Sakai and Yuri Aoki and Masako Yoshimatsu and Kazuhisa Nishishita and Mayumi Iwatake and Yutaka Fukuma and Kuniaki Okamoto and Takashi Tanaka and Takayuki Tsukuba",
year = "2016",
month = "7",
day = "15",
doi = "10.1016/j.phymed.2016.04.002",
language = "English",
volume = "23",
pages = "828--837",
journal = "Phytomedicine",
issn = "0944-7113",
publisher = "Urban und Fischer Verlag Jena",
number = "8",

}

TY - JOUR

T1 - Sanguiin H-6, a constituent of Rubus parvifolius L., inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorption in vitro and prevents tumor necrosis factor-α-induced osteoclast formation in vivo

AU - Sakai, Eiko

AU - Aoki, Yuri

AU - Yoshimatsu, Masako

AU - Nishishita, Kazuhisa

AU - Iwatake, Mayumi

AU - Fukuma, Yutaka

AU - Okamoto, Kuniaki

AU - Tanaka, Takashi

AU - Tsukuba, Takayuki

PY - 2016/7/15

Y1 - 2016/7/15

N2 - Background Osteoclasts are multinucleated bone-resorbing cells that differentiate in response to receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). Enhanced osteoclastogenesis contributes to bone diseases, such as osteoporosis and rheumatoid arthritis. Rubus parvifolius L. is traditionally used as an herbal medicine for rheumatism; however, its detailed chemical composition and the molecular mechanisms responsible for its biological action have not been elucidated. Purpose To investigate the mechanisms by which R. parvifolius L. extract and its major constituent sanguiin H-6, inhibit osteoclastogenesis and bone resorption. Methods Cell proliferation, cell differentiation, and bone resorption were detected in vitro. Inhibition of signaling pathways, marker protein expression, and protein nuclear translocation were evaluated by western blot analysis. Tumor necrosis factor-α (TNF-α)-mediated osteoclastogenesis was examined in vivo. Results R. parvifolius L. extract inhibited the bone-resorption activity of osteoclasts. In addition, sanguiin H-6 markedly inhibited RANKL-induced osteoclast differentiation and bone resorption, reduced reactive oxygen species production, and inhibited the phosphorylation of inhibitor of NF-κB alpha (IκBα) and p38 mitogen-activated protein kinase. Sanguiin H-6 also decreased the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), cathepsin K, and c-Src. Moreover, sanguiin H-6 inhibited the nuclear translocation of NFATc1, c-Fos, and NF-κB in vitro, as well as TNF-α-mediated osteoclastogenesis in vivo. Conclusions Our data revealed that R. parvifolius L. has anti-bone resorption activity and suggest that its constituent, sanguiin H-6, can potentially be used for the prevention and treatment of bone diseases associated with excessive osteoclast formation and subsequent bone destruction.

AB - Background Osteoclasts are multinucleated bone-resorbing cells that differentiate in response to receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). Enhanced osteoclastogenesis contributes to bone diseases, such as osteoporosis and rheumatoid arthritis. Rubus parvifolius L. is traditionally used as an herbal medicine for rheumatism; however, its detailed chemical composition and the molecular mechanisms responsible for its biological action have not been elucidated. Purpose To investigate the mechanisms by which R. parvifolius L. extract and its major constituent sanguiin H-6, inhibit osteoclastogenesis and bone resorption. Methods Cell proliferation, cell differentiation, and bone resorption were detected in vitro. Inhibition of signaling pathways, marker protein expression, and protein nuclear translocation were evaluated by western blot analysis. Tumor necrosis factor-α (TNF-α)-mediated osteoclastogenesis was examined in vivo. Results R. parvifolius L. extract inhibited the bone-resorption activity of osteoclasts. In addition, sanguiin H-6 markedly inhibited RANKL-induced osteoclast differentiation and bone resorption, reduced reactive oxygen species production, and inhibited the phosphorylation of inhibitor of NF-κB alpha (IκBα) and p38 mitogen-activated protein kinase. Sanguiin H-6 also decreased the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), cathepsin K, and c-Src. Moreover, sanguiin H-6 inhibited the nuclear translocation of NFATc1, c-Fos, and NF-κB in vitro, as well as TNF-α-mediated osteoclastogenesis in vivo. Conclusions Our data revealed that R. parvifolius L. has anti-bone resorption activity and suggest that its constituent, sanguiin H-6, can potentially be used for the prevention and treatment of bone diseases associated with excessive osteoclast formation and subsequent bone destruction.

KW - c-Fos

KW - Nuclear factor of activated T cells cytoplasmic-1

KW - Osteoclast

KW - Receptor activator of nuclear factor-κb

KW - Sanguiin H-6

UR - http://www.scopus.com/inward/record.url?scp=84977623111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977623111&partnerID=8YFLogxK

U2 - 10.1016/j.phymed.2016.04.002

DO - 10.1016/j.phymed.2016.04.002

M3 - Article

VL - 23

SP - 828

EP - 837

JO - Phytomedicine

JF - Phytomedicine

SN - 0944-7113

IS - 8

ER -