番红花醛通过靶向 Sirt1 干扰 NF-κB 乙酰化来抑制雌激素缺乏性骨质疏松症,Phytomedicine

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番红花醛通过靶向 Sirt1 干扰 NF-κB 乙酰化来抑制雌激素缺乏性骨质疏松症
Phytomedicine ( IF 6.7 ) Pub Date : 2023-03-05 , 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 ₁ , Gang Zheng ₁ , Nai-Feng Tian ₁

Affiliation

背景

骨质疏松症是更年期常见的骨代谢疾病，长期服药伴随着严重的副作用。雌激素缺乏介导的过度活化的破骨细胞是骨质流失的起始因素，其受核因子-κB（NF-κB）信号传导的调节。藏红花醛 (Saf) 是一种从藏红花 ( Crocus sativus L.)中提取的单萜醛，具有多种生物学特性，尤其是抗炎特性。然而，Saf 在骨质疏松症中的作用仍然未知。

目的

本研究旨在验证Saf在骨质疏松症中的作用并探索其潜在机制。

学习规划

应用RANKL暴露的小鼠BMM（骨髓单核细胞）和去势介导的骨质疏松症模型，探讨Saf在体外和体内的作用和机制。

方法

通过 TRAcP 染色、骨吸收实验、qPCR、免疫印迹和免疫荧光等评估 Saf 对破骨细胞形成和功能的影响。进行显微 CT、HE、TRAcP 和免疫组化染色以评估 Saf 给药对 OVX-在成像和组织学水平上介导的小鼠骨质疏松症。

结果

Saf 浓度依赖性地抑制 RANKL 介导的破骨细胞分化，而不影响细胞活力。同时，在去卵巢小鼠中也发现了 Saf 介导的抗骨溶解能力和 Sirt1 上调。从机制上讲，Saf 通过激活 Sirt1 以增加 p65 去乙酰化和使 IKK 失活以减少 IκBα 降解来干扰 NF-κB 信号传导。

结论

我们的结果支持 Saf 作为骨质疏松症治疗剂的潜在应用。

"点击查看英文标题和摘要"

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

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.