BACKGROUND Since non-alcoholic fatty liver disease (NAFLD) pathogenesis is multi-factorial, pharmacotherapy with a specific target commonly exhibits limited efficacy. Phytotherapy, whose therapeutic efficacy is based on the combined action of several active compounds, offers new treatment opportunity for NAFLD. As a representative, many natural polyphenols could be utilized in phytotherapy for NAFLD. PURPOSE In present work, we aimed to investigate the therapeutic effects and underlying mechanism of polyphenols in blueberry leaves (PBL) on NAFLD from a mitochondria-centric perspective since mitochondrial dysfunction could play a dominant role in NAFLD. METHODS Identification and quantification of PBL were performed using liquid chromatography coupled with tandem mass spectrometry. The beneficial effects, especially improving mitochondrial function, and potential mechanism of PBL on NAFLD were studied by in vitro and in vivo study. RESULTS Polyphenols were abundant in blueberry leaves making it advantaged in NAFLD phytotherapy. PBL effectively alleviated hepatic steatosis, oxidative stress and inflammation as indicated by both in vitro and in vivo study. Furthermore, PBL mediated improvement of mitochondrial dysfunction and antioxidant capability through activation of AMPK/PGC-1α/SIRT3 signaling axis. CONCLUSION Considering that mitochondrial dysfunction takes precedence over hepatic steatosis and induces NAFLD development, we conclude that PBL improve mitochondrial dysfunction and oxidative defense, subsequently alleviate hepatic steatosis, oxidative stress and inflammation, and eventually alleviate NAFLD.

中文翻译：

---

使用蓝莓叶多酚进行的植物疗法可通过改善线粒体功能和氧化防御作用来缓解非酒精性脂肪肝疾病。

背景技术由于非酒精性脂肪肝疾病（NAFLD）发病机理是多因素的，因此具有特定靶标的药物治疗通常显示出有限的功效。植物疗法的疗效基于多种活性化合物的共同作用，为NAFLD提供了新的治疗机会。作为代表，许多天然多酚可用于NAFLD的植物治疗。目的在目前的工作中，我们旨在从线粒体为中心的角度研究蓝莓叶中多酚对NAFLD的治疗作用及其潜在机制，因为线粒体功能障碍可能在NAFLD中起主导作用。方法采用液相色谱-串联质谱法对PBL进行鉴定和定量。有益的作用 通过体外和体内研究，研究了PBL对NAFLD的潜在作用机制，尤其是改善线粒体功能。结果蓝莓叶片中含有丰富的多酚，使其在NAFLD植物疗法中具有优势。如体外和体内研究所示，PBL有效缓解了肝脂肪变性，氧化应激和炎症。此外，PBL通过激活AMPK /PGC-1α/ SIRT3信号轴来介导线粒体功能障碍和抗氧化能力的改善。结论考虑到线粒体功能障碍优先于肝脂肪变性并诱发NAFLD发生，我们得出结论，PBL可改善线粒体功能障碍和氧化防御，从而减轻肝脂肪变性，氧化应激和炎症，并最终缓解NAFLD。通过体外和体内研究研究了PBL对NAFLD的潜在作用机制。结果蓝莓叶片中含有丰富的多酚，使其在NAFLD植物疗法中具有优势。如体外和体内研究所示，PBL有效减轻了肝脂肪变性，氧化应激和炎症。此外，PBL通过激活AMPK /PGC-1α/ SIRT3信号轴来介导线粒体功能障碍和抗氧化能力的改善。结论考虑到线粒体功能障碍优先于肝脂肪变性并诱发NAFLD发生，我们得出结论，PBL可改善线粒体功能障碍和氧化防御，从而减轻肝脂肪变性，氧化应激和炎症，并最终缓解NAFLD。通过体外和体内研究研究了PBL对NAFLD的潜在作用机制。结果蓝莓叶片中含有丰富的多酚，使其在NAFLD植物疗法中具有优势。如体外和体内研究所示，PBL有效缓解了肝脂肪变性，氧化应激和炎症。此外，PBL通过激活AMPK /PGC-1α/ SIRT3信号轴来介导线粒体功能障碍和抗氧化能力的改善。结论考虑到线粒体功能障碍优先于肝脂肪变性并诱发NAFLD发生，我们得出结论，PBL可改善线粒体功能障碍和氧化防御，从而减轻肝脂肪变性，氧化应激和炎症，并最终缓解NAFLD。结果蓝莓叶片中含有丰富的多酚，使其在NAFLD植物疗法中具有优势。如体外和体内研究所示，PBL有效缓解了肝脂肪变性，氧化应激和炎症。此外，PBL通过激活AMPK /PGC-1α/ SIRT3信号轴来介导线粒体功能障碍和抗氧化能力的改善。结论考虑到线粒体功能障碍优先于肝脂肪变性并诱发NAFLD发生，我们得出结论，PBL可改善线粒体功能障碍和氧化防御，从而减轻肝脂肪变性，氧化应激和炎症，并最终缓解NAFLD。结果蓝莓叶片中含有丰富的多酚，使其在NAFLD植物疗法中具有优势。如体外和体内研究所示，PBL有效缓解了肝脂肪变性，氧化应激和炎症。此外，PBL通过激活AMPK /PGC-1α/ SIRT3信号轴来介导线粒体功能障碍和抗氧化能力的改善。结论考虑到线粒体功能障碍优先于肝脂肪变性并诱发NAFLD发生，我们得出结论，PBL可改善线粒体功能障碍和氧化防御，从而减轻肝脂肪变性，氧化应激和炎症，并最终缓解NAFLD。体外和体内研究均表明氧化应激和炎症。此外，PBL通过激活AMPK /PGC-1α/ SIRT3信号轴来介导线粒体功能障碍和抗氧化能力的改善。结论考虑到线粒体功能障碍优先于肝脂肪变性并诱发NAFLD发生，我们得出结论，PBL可改善线粒体功能障碍和氧化防御，从而减轻肝脂肪变性，氧化应激和炎症，并最终缓解NAFLD。体外和体内研究均表明氧化应激和炎症。此外，PBL通过激活AMPK /PGC-1α/ SIRT3信号轴来介导线粒体功能障碍和抗氧化能力的改善。结论考虑到线粒体功能障碍优先于肝脂肪变性并诱发NAFLD发生，我们得出结论，PBL可改善线粒体功能障碍和氧化防御，从而减轻肝脂肪变性，氧化应激和炎症，并最终缓解NAFLD。