Herbal Combination of Angelica gigas, Zingiber officinale, and Aconitum carmichaeli Alleviates High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice Through NRF2-Mediated Regulation of Adipogenesis and Non-Shivering Thermogenesis.

Obesity is a complex metabolic disorder characterized by excessive fat accumulation and is closely associated with non-alcoholic fatty liver disease (NAFLD), a condition that increases the risk of metabolic complications such as insulin resistance, type 2 diabetes, and cardiovascular diseases. JI017 is a recently optimized multi-herbal formula composed of Angelica gigas, Zingiber officinale , and processed Aconitum carmichaeli. Clinical records of these three herbs indicate their potentially synergistic anti-obesity effects. This study was conducted to verify the effects of JI017 in an animal model of obesity-associated NAFLD. The effect of JI017 on glucose metabolism, white adipose tissue (WAT) adipogenesis, brown adipose tissue (BAT) thermogenesis, liver oxidative stress, and gut microbiota composition was assessed. The results showed that JI017 improved glucose sensitivity, reduced WAT mass by suppressing PPARγ and C/EBPα expression, and increased BAT thermogenesis through upregulation of UCP1 and PGC-1α. Additionally, JI017 reduced liver oxidative stress by increasing HO-1 and NRF2 expression and modulated the gut microbiota by restoring the Firmicutes/Bacteroidetes ratio. These findings on the multi-targeted effects of JI017 suggest its potential as a promising therapeutic approach for metabolic diseases including NAFLD.