Aerial Yam Bulbils Protect Against APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Mitochondrial Dysfunction Through Nrf2 Activation

山药球茎通过激活Nrf2抑制氧化应激和线粒体功能障碍,从而保护肝脏免受对乙酰氨基酚(APAP)诱导的肝毒性损伤。

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Abstract

BACKGROUND/OBJECTIVES: The extract from aerial yam bulbils (AYB) contains various bioactive compounds, yet the mechanisms underlying its effects on APAP-induced liver injury need to be investigated further. This study sought to pursue the effects of AYB extract and the potential mechanisms involved in mitigating APAP-induced hepatotoxicity. METHODS: TIB-73 cells were pretreated with AYB extract (10, 20, and 40 μg/mL) for 24 h and treated with APAP for 24 h to induce cytotoxicity. RESULTS: Analysis of apoptosis-related proteins revealed that AYB extract exerts anti-apoptotic effects and inhibiting the MAPK signaling pathways, thereby reducing apoptotic cell death. Additionally, AYB extract significantly suppressed ROS overproduction by enhancing the expression of endogenous antioxidants and reducing the endoplasmic reticulum (ER) stress in APAP-treated cells, indicating that AYB extract inhibits APAP-induced oxidative stress. AYB extract effectively preserved mitochondrial membrane potential (MMP), maintained mitochondrial function-related genes, reduced mitochondrial oxidative stress, and mitigated mitochondrial damage, thereby preserving mitochondrial integrity. Additionally, AYB extract activated the Nrf2-related signaling pathway through nuclear translocation, leading to the upregulation of downstream antioxidative target genes. Diosgenin, a compound with known antioxidant properties and hepatoprotective effects, was identified in significant quantities in the AYB extract, suggesting that it may contribute to the observed hepatoprotective effects. CONCLUSIONS: Overall, these findings demonstrate that AYB extract, with its antioxidative properties, effectively protects TIB-73 cells from APAP-induced liver injury.

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