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桃叶珊瑚苷可在体外保护软骨细胞免受白细胞介素-1β诱导的凋亡，并在小鼠模型中抑制骨关节炎。

Aucubin Protects Chondrocytes Against IL-1β-Induced Apoptosis In Vitro And Inhibits Osteoarthritis In Mice Model.

作者信息

Wang Bo-Wei, Jiang Yi, Yao Zi-Long, Chen Pei-Sheng, Yu Bin, Wang Sheng-Nan

机构信息

Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.

Department of Orthopaedics, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, Fujian 350007, People's Republic of China.

出版信息

Drug Des Devel Ther. 2019 Oct 9;13:3529-3538. doi: 10.2147/DDDT.S210220. eCollection 2019.

DOI:10.2147/DDDT.S210220
PMID:31631977
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6791845/
Abstract

OBJECTIVE: Chondrocyte apoptosis has also been strongly correlated with the severity of cartilage damage and matrix depletion in an osteoarthritis (OA) joint. Therefore, pharmacological inhibitors of apoptosis may provide a novel treatment option for patients with OA. Aucubin, a natural compound isolated from , has been proved to possess antioxidative and anti-apoptotic properties. However, anti-osteoarthritis effect of aucubin in animal model and anti-apoptotic response of aucubin in OA chondrocytes remain unclear. This study aimed to determine whether aucubin could slow progression of OA in a mouse model and inhibit the IL-1β-induced chondrocyte apoptosis. METHODS: OA severity and articular cartilage degradation were evaluated by Safranin-O staining, Hematoxylin-eosin (H&E) staining, and Osteoarthritis Research Society International (OARSI) standards. Chondrocyte viability was observed by Cell Counting Kit-8 (CCK8) and live/dead cells assay; the apoptotic rate of chondrocytes was evaluated by flow cytometry (FCM) with Annexin V-FITC/PI kit. Mediators of apoptosis were tested by Western blot of Bax, caspase-3, caspase-9, and Bcl-2 expression. The intracellular levels of Reactive oxygen species (ROS) were assessed by the probe of 2,7-Dichlorofluorescin diacetate (DCFH-DA). RESULTS: The articular cartilage in the limb with destabilization of the medial meniscus (DMM) exhibited early OA-like manifestations characterized by proteoglycan loss, cartilage fibrillation, and erosion, with lower OARSI score. Oral administration of aucubin remarkably attenuated the loss of proteoglycan and the articular cartilage erosion and decreased the OARSI scores underwent DMM surgery. Aucubin treatment significantly reverses IL-1β-induced cytotoxicity and attenuated the IL-1β-induced chondrocyte apoptosis. In addition, aucubin can significantly inhibit mediators of apoptosis in rat primary chondrocytes. Furthermore, aucubin remarkably attenuated the IL-1β-induced intracellular ROS production. CONCLUSION: Our findings suggest that aucubin has a protective effect on articular cartilage and slowing progression of OA in a mouse model. This protective effect may result from inhibiting chondrocyte apoptosis and excessive ROS production.

摘要

目的：软骨细胞凋亡也与骨关节炎（OA）关节中软骨损伤的严重程度和基质消耗密切相关。因此，凋亡的药理学抑制剂可能为OA患者提供一种新的治疗选择。桃叶珊瑚苷是从[具体来源未给出]中分离出的一种天然化合物，已被证明具有抗氧化和抗凋亡特性。然而，桃叶珊瑚苷在动物模型中的抗骨关节炎作用以及在OA软骨细胞中的抗凋亡反应仍不清楚。本研究旨在确定桃叶珊瑚苷是否能减缓小鼠模型中OA的进展并抑制IL-1β诱导的软骨细胞凋亡。 方法：通过番红O染色、苏木精-伊红（H&E）染色和国际骨关节炎研究学会（OARSI）标准评估OA严重程度和关节软骨降解。通过细胞计数试剂盒-8（CCK8）和活/死细胞测定观察软骨细胞活力；使用膜联蛋白V-异硫氰酸荧光素/碘化丙啶（PI）试剂盒通过流式细胞术（FCM）评估软骨细胞的凋亡率。通过对Bax、半胱天冬酶-3、半胱天冬酶-9和Bcl-2表达进行蛋白质印迹法检测凋亡介质。使用二氯荧光素二乙酸酯（DCFH-DA）探针评估细胞内活性氧（ROS）水平。 结果：内侧半月板不稳定（DMM）肢体的关节软骨表现出早期OA样表现，其特征为蛋白聚糖丢失、软骨纤维化和侵蚀，OARSI评分较低。口服桃叶珊瑚苷可显著减轻蛋白聚糖的丢失和关节软骨侵蚀，并降低接受DMM手术的小鼠的OARSI评分。桃叶珊瑚苷治疗可显著逆转IL-1β诱导的细胞毒性，并减轻IL-1β诱导的软骨细胞凋亡。此外，桃叶珊瑚苷可显著抑制大鼠原代软骨细胞中的凋亡介质。此外，桃叶珊瑚苷可显著减轻IL-1β诱导的细胞内ROS产生。 结论：我们的研究结果表明，桃叶珊瑚苷对关节软骨具有保护作用，并可减缓小鼠模型中OA的进展。这种保护作用可能是由于抑制软骨细胞凋亡和过量的ROS产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbe/6791845/1d7960745b16/DDDT-13-3529-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbe/6791845/9da859e34e5f/DDDT-13-3529-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbe/6791845/0eaacd8905a8/DDDT-13-3529-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbe/6791845/7c89c634dec7/DDDT-13-3529-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bbe/6791845/1d7960745b16/DDDT-13-3529-g0007.jpg

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本文引用的文献

[1]
The therapeutic effect of aucubin-supplemented hyaluronic acid on interleukin-1beta-stimulated human articular chondrocytes.

Phytomedicine. 2018-10-2

[2]
Aucubin suppresses Titanium particles‑mediated apoptosis of MC3T3‑E1 cells and facilitates osteogenesis by affecting the BMP2/Smads/RunX2 signaling pathway.

Mol Med Rep. 2018-7-16

[3]
Paeonol alleviates interleukin-1β-induced inflammatory responses in chondrocytes during osteoarthritis.

Biomed Pharmacother. 2017-9-10

[4]
Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus.

BMC Complement Altern Med. 2017-2-2

[5]
Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis.

Int J Mol Sci. 2016-12-20

[6]
Role of ROS and RNS Sources in Physiological and Pathological Conditions.

Oxid Med Cell Longev. 2016

[7]
Gold Nanoparticles of Diameter 13 nm Induce Apoptosis in Rabbit Articular Chondrocytes.

Nanoscale Res Lett. 2016-5-13

[8]
ROS/oxidative stress signaling in osteoarthritis.

Biochim Biophys Acta. 2016-4

[9]
Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis.

Int J Mol Sci. 2015-10-30

[10]
Aucubin prevents interleukin-1 beta induced inflammation and cartilage matrix degradation via inhibition of NF-κB signaling pathway in rat articular chondrocytes.

Int Immunopharmacol. 2015-2

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