<br>Geniposide 通过 PINK1/Parkin 信号通路激活线粒体自噬，有效保护 HT22 细胞免受 Aβ 诱导的损伤,BIOCHEMICAL PHARMACOLOGY

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Geniposide 通过 PINK1/Parkin 信号通路激活线粒体自噬，有效保护 HT22 细胞免受 Aβ 诱导的损伤
BIOCHEMICAL PHARMACOLOGY ( IF 5.3 ) Pub Date : 2024-05-16 , DOI: 10.1016/j.bcp.2024.116296
Jiaxi Ye ₁ , Jiaying Wu ₁ , Liang Ai ₁ , Min Zhu ₁ , Yun Li ₂ , Dong Yin ₂ , Qihui Huang ₁

Affiliation

阿尔茨海默病（AD）是一种神经退行性疾病，其特征是淀粉样蛋白-β （Aβ）肽在其发病机制中显著参与。Geniposide 源自 Gardenia jasminoides 的多功能药用，是被广泛研究的活性化合物之一。目的是探讨京尼泊苷对 Aβ25-35 诱导的 HT22 细胞损伤的影响，特别关注其对 PINK1/Parkin 介导的线粒体自噬的调节。在我们的研究中，京尼泊苷通过增强细胞活力和保留线粒体膜电位表现出显着的恢复作用。此外，它有效减少和减轻了 Aβ25-35 诱导的氧化应激和细胞凋亡率。值得注意的是，京尼泊苷表现出增强自噬通量、上调 LC3II 和 Beclin-1 表达以及下调 p62 表达的能力。此外，京尼泊苷对 PINK1 和 Parkin 蛋白的表达产生积极影响，分子对接证实了京尼泊苷和 PINK1/Parkin 蛋白之间的强烈相互作用。有趣的是，京尼泊苷在缓解 Aβ25-35 诱导的显着细胞凋亡率、活性氧过量产生以及减少 PINK1 和 Parkin 表达方面的有益结果被线粒体自噬抑制剂环孢菌素 A （CsA）损害。总的来说，这些发现表明，京尼泊苷可能通过激活线粒体自噬保护 HT22 细胞免受 Aβ25-35 触发的神经退行性损伤。这些见解为京尼泊苷对神经损伤的防御后果提供了有价值的参考，从而突出了其作为 AD 治疗干预的潜力。

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Geniposide effectively safeguards HT22 cells against Aβ-induced damage by activating mitophagy via the PINK1/Parkin signaling pathway

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the significant involvement of amyloid-beta (Aβ) peptide in its pathogenesis. Geniposide, derived from the versatile medicinal of Gardenia jasminoides, is one of the active compounds studied extensively. The objective was to explore the impact of geniposide on Aβ25-35-induced damage in HT22 cells, specifically focusing on its modulation of PINK1/Parkin-mediated mitophagy. In our investigation, geniposide exhibited remarkable restorative effects by enhancing cell viability and preserving the mitochondrial membrane potential. Moreover, it effectively reduced and mitigated the oxidative stress and apoptosis rates induced by Aβ25-35. Notably, geniposide exhibited the capacity to enhance autophagic flux, upregulate LC3II and Beclin-1 expression, and downregulate the expression of p62. Furthermore, geniposide positively influenced the expression of PINK1 and Parkin proteins, with molecular docking substantiating a strong interaction between geniposide and PINK1/Parkin proteins. Intriguingly, the beneficial outcomes of geniposide on alleviating the pronounced apoptosis rates, the overproduction of reactive oxygen species, and diminished the PINK1 and Parkin expression induced by Aβ25-35 were compromised by the mitophagy inhibitor cyclosporine A (CsA). Collectively, these findings suggested that geniposide potentially shields HT22 cells against neurodegenerative damage triggered by Aβ25-35 through the activation of mitophagy. The insights contribute valuable references to the defensive consequences against neurological damage of geniposide, thereby highlighting its potential as a therapeutic intervention in AD.

更新日期：2024-05-16

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