Ajugol's upregulation of TFEB-mediated autophagy alleviates endoplasmic reticulum stress in chondrocytes and retards osteoarthritis progression in a mouse model.

Autor: Wu, Jingtao, Yu, Heng, Jin, Yangcan, Wang, Jingquan, Zhou, Liwen, Cheng, Teng, Zhang, Zhao, Lin, Binghao, Miao, Jiansen, Lin, Zhongke
Předmět:
Zdroj: Chinese Medicine; 9/7/2023, Vol. 18 Issue 1, p1-16, 16p
Abstrakt: Background: Osteoarthritis (OA), a degenerative disease with a high global prevalence, is characterized by the degradation of the extracellular matrix (ECM) and the apoptosis of chondrocytes. Ajugol, a extract derived from the herb Rehmannia glutinosa, has not yet been investigated for its potential in modulating the development of OA. Methods: We employed techniques such as western blotting, immunofluorescence, immunohistochemistry, X-ray imaging, HE staining, and SO staining to provide biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery. Results: Our findings revealed that treatment with 50 μM Ajugol activated TFEB-mediated autophagy, alleviating ER stress-induced chondrocyte apoptosis and ECM degradation caused by TBHP. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery. Conclusion: These results provide compelling biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA by activating autophagy and attenuating ER stress-induced cell death and ECM degradation. The promising in vivo results further suggest the potential of Ajugol as a treatment strategy for OA progression. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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