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阳和汤通过AMPK-SIRT3正反馈环介导的线粒体自噬减轻骨关节炎。

Yanghe decoction alleviates osteoarthritis by AMPK-SIRT3 positive feedback loop-mediated mitochondrial autophagy.

作者信息

Shi Peng-Bo, Du Meng-Meng, Yu Peng, Bu Xian-Zhong, Meng Dong-Fang, Qiao Wei-Ping, Wang Li-He, Li Hui-Ying

机构信息

Department of Orthopedics, The First Afliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, China; Engineering Research Center For Traditional Chinese Orthopedics Characteristic Technology and Equipment by Henan Province, Zhengzhou, 450000, China.

Department of Orthopedics, The First Afliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, China.

出版信息

J Ethnopharmacol. 2025 Feb 11;341:119294. doi: 10.1016/j.jep.2024.119294. Epub 2024 Dec 31.

DOI:10.1016/j.jep.2024.119294
PMID:39746407
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Yanghe Decoction(YHD) is a traditional Chinese medicine compound known for its efficacy in treating osteoarthritis (OA).

AIM OF THE STUDY

We aimed to explore the underlying mechanisms of YHD in relation to OA.

MATERIALS AND METHODS

UHPLC-MS technology was used to identify the material basis of YHD. In vivo, OA rat model was induced by the modified Hulth method and then treated with YHD at three different doses (0.625, 1.3 and 2.6 g/kg/d). In vitro,YHD-Contained serum was prepared and administrated into rat chondrocytes, followed by simulation of Lipopolysaccharide(LPS). The protective mechanism was determined by observation of morphology, Flow cytometry and Protein level detection.

RESULTS

In vivo, YHD reduced chondrocyte apoptosis and joint inflammation while promoting mitophagy. It also elevated the protein levels of p-AMPK, SIRT3, PINK1, Parkin, and LC3II/I. In vitro, YHD-Contained Serum reduced chondrocyte apoptosis, decreased mitochondrial ROS, enhanced mitochondrial membrane potential, and upregulated the protein expressions of p-AMPK, SIRT3, PINK1, Parkin, and LC3II/I.

CONCLUSION

Through this study, we demonstrated YHD protect chondrocytes against apoptosis, and its underlying mechanisms may involve the regulation of AMPK-SIRT3 positive feedback loop and activation of PINK1/Parkin mediated mitophagy.

摘要

民族药理学相关性

阳和汤(YHD)是一种传统中药复方,以其治疗骨关节炎(OA)的功效而闻名。

研究目的

我们旨在探讨阳和汤治疗OA的潜在机制。

材料与方法

采用超高效液相色谱-质谱联用(UHPLC-MS)技术鉴定阳和汤的物质基础。在体内,通过改良的 Hulth 方法诱导 OA 大鼠模型,然后用三种不同剂量(0.625、1.3 和 2.6 g/kg/d)的阳和汤进行治疗。在体外,制备含阳和汤血清并将其作用于大鼠软骨细胞,随后模拟脂多糖(LPS)刺激。通过观察形态、流式细胞术和蛋白质水平检测来确定保护机制。

结果

在体内,阳和汤减少软骨细胞凋亡和关节炎症,同时促进线粒体自噬。它还提高了 p-AMPK、SIRT3、PINK1、Parkin 和 LC3II/I 的蛋白质水平。在体外,含阳和汤血清减少软骨细胞凋亡,降低线粒体活性氧(ROS),增强线粒体膜电位,并上调 p-AMPK、SIRT3、PINK1、Parkin 和 LC3II/I 的蛋白质表达。

结论

通过本研究,我们证明阳和汤可保护软骨细胞免受凋亡,其潜在机制可能涉及对 AMPK-SIRT3 正反馈回路的调节以及 PINK1/Parkin 介导的线粒体自噬的激活。

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