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Oroxin B 通过抑制破骨细胞的形成和活性来减轻卵巢切除引起的骨丢失。

Oroxin B Attenuates Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Formation and Activity.

机构信息

Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

出版信息

Drug Des Devel Ther. 2021 Nov 30;15:4811-4825. doi: 10.2147/DDDT.S328238. eCollection 2021.

Abstract

BACKGROUND

Osteoclasts are the major players in bone resorption and have always been studied in the prevention and treatment of osteoporosis. Previous studies have confirmed that a variety of flavonoids inhibit osteoporosis and improve bone health mainly through inhibiting osteoclastogenesis. Oroxin B (OB) is a flavonoid compound extracted from traditional Chinese herbal medicine (L.) Vent, exerts potent antitumor and anti-inflammation effect, but its effect on osteoclastogensis remains unknown.

METHODS

We comprehensively evaluated the effect of OB on the formation and function of osteoclasts and the underling mechanism by bone marrow-derived macrophage in vitro. In vivo, we used mice ovariectomized model to verify the protective effect of OB.

RESULTS

OB was found to inhibit osteoclast formation and bone resorption function in vitro, in a dose-dependent manner and the increased osteoclastic-related genes induced by RANKL (NFATc1, c-fos, cathepsin K, RANK, MMP9 and TRAP) were also attenuated following OB treatment. Mechanistical investigation showed OB abrogated the increased phosphorylation level of MAPK and NF-κB pathway, and diminished the expression of the vital transcription factors for osteoclastogenesis. OB also prevented ovariectomy (OVX)-induced bone loss by inhibiting osteoclast formation and activity in mice.

CONCLUSION

Our study demonstrated that OB may act as an anti-osteoporosis agent by inhibiting osteoclast maturation and attenuating bone resorption.

摘要

背景

破骨细胞是骨吸收的主要参与者,一直是预防和治疗骨质疏松症的研究对象。先前的研究已经证实,多种黄酮类化合物通过抑制破骨细胞生成来预防和治疗骨质疏松症,改善骨骼健康。奥洛辛 B(OB)是从传统中药(L.)Vent 中提取的一种黄酮类化合物,具有很强的抗肿瘤和抗炎作用,但它对破骨细胞生成的影响尚不清楚。

方法

我们通过体外骨髓来源的巨噬细胞全面评估了 OB 对破骨细胞形成和功能的影响及其潜在机制。在体内,我们使用去卵巢小鼠模型来验证 OB 的保护作用。

结果

OB 被发现能够抑制体外破骨细胞的形成和骨吸收功能,呈剂量依赖性,并且能够减弱 RANKL(NFATc1、c-fos、组织蛋白酶 K、RANK、MMP9 和 TRAP)诱导的破骨细胞相关基因的增加。机制研究表明,OB 阻断了 MAPK 和 NF-κB 通路的磷酸化水平的增加,并减少了破骨细胞生成的关键转录因子的表达。OB 还通过抑制破骨细胞的形成和活性来预防去卵巢(OVX)诱导的小鼠骨丢失。

结论

我们的研究表明,OB 可能通过抑制破骨细胞成熟和减弱骨吸收来发挥抗骨质疏松作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a7c/8643139/3b1146c66ea1/DDDT-15-4811-g0001.jpg

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