Farrerol suppresses osteoclast differentiation and postmenopausal osteoporosis by inhibiting the nuclear factor kappa B signaling pathway.

Abstract

Excessive bone resorption caused by upregulated osteoclast activity is a key factor in osteoporosis pathogenesis. Farrerol is a typical natural flavanone and exhibits various pharmacological actions. However, the role and mechanism of action of farrerol in osteoclast differentiation regulation remain unclear. This study aimed to evaluate the effects and mechanism of farrerol on the inhibition of osteoclastogenesis. Tartrate-resistant acid phosphatase staining, F-actin staining, and the pit formation assay were performed to examine the differentiation and functions of osteoclasts in vitro. The expression of proteins associated with the nuclear factor kappa B and mitogen-activated protein kinase signaling pathways was analyzed by western blotting. Dual X-ray absorptiometry, microcomputed tomography, and histopathological and immunohistochemical analyses were performed to determine the therapeutic effect of farrerol in vivo bone loss prevention. The effects of farrerol on osteoblastic bone formation were assessed using alkaline phosphatase, alizarin red S staining, and calcein-alizarin red S double labeling. Farrerol inhibited osteoclastogenesis and bone resorption in osteoclasts by suppressing nuclear factor kappa B signaling rather than mitogen-activated protein kinase signaling in vitro. Farrerol protected mice against ovariectomy-induced bone loss by inhibiting osteoclast-mediated bone resorption, instead of promoting osteoblast-mediated bone formation in vivo. The findings of the current study revealed that farrerol is a potential therapeutic agent for osteoporosis.

• Authors: Wei Lu, Guobin Qi, Xiuying Yang, Defang Li, Weibin Chen, Qingmin Zeng, Zengxin Jiang
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 154 Issue 2 Pg. 113-126 (Feb 2024) ISSN: 1347-8648 [Electronic] Japan
• PMID: 38246725 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• NF-kappa B
• alizarin
• farrerol
• Mitogen-Activated Protein Kinases
• Anthraquinones
• Chromones

Topics

• Female
• Humans
• Animals
• Mice
• NF-kappa B
• Osteoclasts
• Osteoporosis, Postmenopausal (drug therapy)
• X-Ray Microtomography
• Signal Transduction
• Osteoporosis (drug therapy)
• Mitogen-Activated Protein Kinases
• Bone Resorption (drug therapy)
• Anthraquinones
• Chromones