Editor's Note
The authors of this study investigate investigate the therapeutic effects and underlying mechanism of polyphenols in blueberry leaves (PBL) on non-alcoholic fatty liver disease (NAFLD) from a mitochondria-centric perspective since mitochondrial dysfunction could play a dominant role in NAFLD. The authors hypothesize that phytotherapy, with therapeutic efficacy based on the combined action of several active compounds, could offer a new treatment opportunity for NAFLD. The study notes since NAFLD pathogenesis is multi-factorial, pharmacotherapy with a specific target commonly exhibits limited efficacy. Based on the results of this study, the authors concluded that PBL improve mitochondrial dysfunction and oxidative defense, subsequently alleviate hepatic steatosis, oxidative stress and inflammation, and eventually alleviate NAFLD.
Abstract

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.

Graphical abstract
2020 Annual Fund Sponsors: