2. Academic Validation
  3. Safranal inhibits estrogen-deficiency osteoporosis by targeting Sirt1 to interfere with NF-κB acetylation

Safranal inhibits estrogen-deficiency osteoporosis by targeting Sirt1 to interfere with NF-κB acetylation

  • Phytomedicine. 2023 Jun:114:154739. doi: 10.1016/j.phymed.2023.154739.
Sun-Ren Sheng 1,  Yu-Hao Wu 1,  Zi-Han Dai 1,  Chen Jin 1,  Gao-Lu He 1,  Shu-Qing Jin 1,  Bi-Yao Zhao 1,  Xin Zhou 1,  Cheng-Long Xie 2,  Gang Zheng 3,  Nai-Feng Tian 4
Affiliations

Affiliations

  • 1 Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, 270# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China.
  • 2 Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, 270# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China. Electronic address: [email protected].
  • 3 Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, 270# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China. Electronic address: [email protected].
  • 4 Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, 270# Xueyuan Road, Wenzhou 325000, Zhejiang Province, China. Electronic address: [email protected].
PMID: 37004404 DOI: 10.1016/j.phymed.2023.154739
Abstract

Background: Osteoporosis is a prevalent bone Metabolic Disease in menopause, and long-term medication is accompanied by serious side effects. Estrogen deficiency-mediated hyperactivated osteoclasts is the initiating factor for bone loss, which is regulated by nuclear factor-κB (NF-κB) signaling. Safranal (Saf) is a monoterpene aldehyde produced from Saffron (Crocus sativus L.) and possesses multiple biological properties, particularly the anti-inflammatory property. However, Saf's role in osteoporosis remains unknown.

Purpose: This study aims to validate the role of Saf in osteoporosis and explore the potential mechanism.

Study design: The RANKL-exposed mouse BMM (bone marrow monocytes) and the castration-mediated osteoporosis model were applied to explore the effect and mechanism of Saf in vitro and in vivo.

Method: The effect of Saf on osteoclast formation and function were assessed by TRAcP staining, bone-resorptive experiment, qPCR, immunoblotting and immunofluorescence, etc. Micro-CT, HE, TRAcP and immunohistochemical staining were performed to estimate the effects of Saf administration on OVX-mediated osteoporosis in mice at imaging and histological levels.

Results: Saf concentration-dependently inhibited RANKL-mediated osteoclast differentiation without affecting cellular viability. Meanwhile, Saf-mediated anti-osteolytic capacity and SIRT1 upregulation were also found in ovariectomized mice. Mechanistically, Saf interfered with NF-κB signaling by activating SIRT1 to increase p65 deacetylation and inactivating IKK to decrease IκBα degradation.

Conclusion: Our results support the potential application of Saf as a therapeutic agent for osteoporosis.

Keywords

Acetylation; Osteoclast; Osteoporosis; Safranal; Sirt1.

Figures
Products