ReferenceID 5392
Hederagenin protects mice against ovariectomy-induced bone loss by inhibiting RANKL-induced osteoclastogenesis and bone resorption
Life Sci
AIMS: Postmenopausal osteoporosis and other osteolytic bone diseases are often caused by the elevation in osteoclastogenesis and/or increased osteoclastic bone resorption, leading to excessive bone loss. Hederagenin (Hed
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Record Fields
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- Reference Id
- 5392
- Evidence Id
- 21982
- Core Evidence Id
- 21982
- Source Reference Id
- 4043
- Herb2 Reference Id
- HBREF004840
- Subject Paper Key
- HBIN028847_31972206
- Pubmed Id
- 31972206
- Doi
- 10.1016/j.lfs.2020.117336
- Paper Title
- Hederagenin protects mice against ovariectomy-induced bone loss by inhibiting RANKL-induced osteoclastogenesis and bone resorption
- Paper Abstract
- AIMS: Postmenopausal osteoporosis and other osteolytic bone diseases are often caused by the elevation in osteoclastogenesis and/or increased osteoclastic bone resorption, leading to excessive bone loss. Hederagenin (Hed) is a pentacyclic triterpenoid saponin extracted from various natural medicinal plants and exhibits numerous biological activities and may offer benefits against bone-related conditions. We evaluated the effects of Hed on osteoclast formation and bone resorption in vitro and the in vivo therapeutic benefits in the mouse model of ovariectomy (OVX)-induced bone loss. MAIN METHODS: In vitro, osteoclast formation were determined by TRAcp staining; bone resorption were examined using Hydroxyapatite resorption assay and Podosomal actin belt formation assay; Related molecular mechanisms were determined by western blot assay. Construction of OVX mice by bilateral oophorectomy to simulate bone loss in vivo. KEY FINDINGS: In vitro cellular assays showed that Hed inhibited RANKL-induced osteoclast formation and osteoclast bone (hydroxyapatite) resorption as well as marker gene expression from BMM culture. Mechanistically, Hed attenuated RANKL-induced intracellular reactive oxygen species (ROS) production, and MAPK signaling pathway (ERK and p38) activation which curbed the downstream induction of c-Fos and NFATc1. Consistent with the in vitro findings, Hed administration effectively protected OVX mice from bone loss by reducing osteoclast number and activity on bone surface. SIGNIFICANCE: Our data provided promising evidence for the potential use of Hederagenin in the treatment of osteoclast-mediated osteolytic bone diseases such as postmenopausal osteoporosis.
- Journal
- Life Sci
- Publish Year
- 2020
- Experiment Subject
- mouse; bmm culture
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Ovariectomy; Osteoclast-mediated Osteolytic Bone Diseases; Postmenopausal Osteoporosis; Osteolytic Bone Diseases; Excessive Bone Loss
- Paper Title Cn
- Paper Title En
- Hederagenin protects mice against ovariectomy-induced bone loss by inhibiting RANKL-induced osteoclastogenesis and bone resorption
- Bilingual Status
- semi_complete