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.
- 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].
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.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Keap1-Nrf2