Morusin Inhibits RANKL-induced Osteoclastogenesis and Ovariectomized Osteoporosis

Comb Chem High Throughput Screen. 2024;27(9):1358-1370. doi: 10.2174/0113862073252310230925062415.

Abstract

Background: Postmenopausal osteoporosis (PMOP) is a classic type of osteoporosis that has gradually become a significant health problem worldwide. There is an urgent need for a safe alternative therapeutic agent considering the poor therapeutic strategies currently available for this disease. The roots and bark of the Morus australis tree (Moraceae) are used to make a traditional Chinese medicine known as "Morusin", and accumulating evidence has demonstrated its multiple activities, such as anti-inflammatory and anti-tumor effects.

Objective: In this study, we aim to explore the effect of Morusin on mouse osteoclasts and its mechanism.

Methods: In this study, we explored the inhibitory effects of Morusin on murine osteoclasts in vitro and its mechanism, and the protective effect of Morusin on an ovariectomy (OVX)-induced osteoporosis model in vivo.

Results: The results showed that Morusin prevented OVX-induced bone loss and dramatically decreased RANKL-induced osteoclastogenesis. Morusin interfered with RANKL-activated NF- κB, MAPK, and PI3K/AKT signaling pathways. The expression of three master factors that control osteoclast differentiation, c-Fos, NFATc1, and c-Jun, was reduced by Morusin treatment. Collectively, in vitro results indicated that Morusin has a protective effect on OVX-induced bone loss in a mouse model.

Conclusion: Our data provide encouraging evidence that Morusin may be an effective treatment for PMOP.

Keywords: Postmenopausal osteoporosis; RANKL.; moraceae; morusin; osteoclastogenesis; osteoclasts.

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Osteoclasts* / drug effects
  • Osteogenesis* / drug effects
  • Osteoporosis / drug therapy
  • Osteoporosis, Postmenopausal / drug therapy
  • Ovariectomy*
  • RANK Ligand* / metabolism
  • RANK Ligand* / pharmacology
  • Signal Transduction / drug effects

Substances

  • morusin
  • RANK Ligand
  • Flavonoids