Isorhapontigenin delays senescence and matrix degradation of nucleus pulposus cells via PI3K/AKT/mTOR-mediated autophagy pathway in vitro and alleviates intervertebral disc degeneration in vivo

异山梨苷元体外通过 PI3K/AKT/mTOR 介导的自噬通路延缓髓核细胞衰老和基质降解,体内减轻椎间盘退变

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作者:Ze Wang, Jiawei Ma, Yun Sun, Zebin Jin, Rukang Zheng, Yuanyuan Li, Heng Yu, Haobo Ye, Yaosen Wu, Xinjiang Ge, Zexin Chen

Abstract

Intervertebral disc degeneration (IVDD), a common degenerative disc disease, is a major etiological factor for back pain, affecting a significant number of middle-aged and elderly individuals worldwide. Thus, IVDD is a major socio-economic burden. The factors contributing to the complex IVDD etiology, which has not been elucidated, include inflammation, oxidative stress, and natural aging. In particular, inflammation and aging of nucleus pulposus cells are considered primary pathogenic factors. Isorhapontigenin (ISO) is a polyphenolic compound commonly found in traditional Chinese herbs and grapes. We have demonstrated that ISO exerts anti-inflammatory and anti-aging effects and mitigates extracellular matrix (ECM) degradation. In this study, in vitro experiments revealed that, ISO delays aging and ECM degradation by promoting PI3K/AKT/mTOR-mediated autophagy. Meanwhile, in vivo experiments affirmed that ISO delays the progression of IVDD.

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