1. Academic Validation
  2. Therapeutic potential of Sweroside in postmenopausal osteoporosis: Inhibition of osteoclast differentiation and promotion of osteoclast apoptosis via NF-κB and MAPK pathways

Therapeutic potential of Sweroside in postmenopausal osteoporosis: Inhibition of osteoclast differentiation and promotion of osteoclast apoptosis via NF-κB and MAPK pathways

  • Int Immunopharmacol. 2025 May 16:155:114630. doi: 10.1016/j.intimp.2025.114630.
Zhipeng Wu 1 Jinquan Wang 2 Kaiye Chen 1 Qing Yu 1 Xijie Zhou 1 Long Wu 1 Chenghao Sun 3
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
  • 2 Department of Orthopaedics, Dongyang People's Hospital, Wenzhou Medical University Affiliated Dongyang Hospital, Dongyang, Zhejiang Province, China.
  • 3 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China. Electronic address: sunchenghaosmith@hotmail.com.
Abstract

Postmenopausal osteoporosis (PMOP) is a common metabolic bone disorder resulting from disrupted bone remodeling due to estrogen deficiency, leading to an increased risk of fractures in postmenopausal women. Sweroside, a natural compound derived from lonicerae japonicae flos, has demonstrated neuroprotective and antioxidant properties, yet its effects on PMOP remain underexplored. In vitro studies indicated that Sweroside inhibited osteoclast differentiation and bone resorption in a concentration-dependent manner. Further investigations revealed that these effects were linked to the suppression of osteoclast-specific gene expression, the modulation of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways, and the promotion of osteoclast Apoptosis via p53 activation. Additionally, in vivo experiments using ovariectomized (OVX) mice showed that Sweroside alleviated bone loss and enhanced bone density. Overall, these findings suggest that Sweroside could be a promising therapeutic candidate for PMOP by modulating critical signaling pathways to inhibit osteoclast formation and bone resorption.

Keywords

Apoptosis; MAPK; NF-κB; Osteoclast differentiation; Postmenopausal osteoporosis; Sweroside.

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