Polygonum cuspidatum extract attenuates fructose-induced liver lipid accumulation through inhibiting Keap1 and activating Nrf2 antioxidant pathway.

Polygonum cuspidatum has been used in traditional Chinese medicine to treat liver disorders associated with oxidative stress, inflammation and lipid accumulation for centuries in patients.The aim of this study was to examine whether P. cuspidatum extract (PCE) prevented against fructose-induced liver lipid accumulation via regulating Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.PCE was administered orally to male Sprague-Dawley rats given 10% fructose drinking water for 6 weeks at 80 and 160 mg/kg once daily for 11 weeks.

PCE significantly alleviated liver lipid accumulation in fructose-fed rats with metabolic syndrome. It also inhibited Keap1, activated Nrf2 antioxidant pathway, resulting in the suppression of oxidative stress, evidenced by reducing hydrogen peroxide (H₂O₂), malondialdehyde (MDA) and hydroxy radical (OH^•) levels, and increasing glutathione (GSH)/oxidized glutathione (GSSG) ratio as well as superoxidase dismutase (SOD) and catalase (CAT) activity in the liver of fructose-fed rats. Additionally, PCE up-regulated peroxisome proliferator activated receptor-α (PPAR-α), and down-regulated sterol regulatory element binging protein 1 (SREBP-1), fatty acid synthetase (FAS) and stearoyl-CoA desaturase-1 (SCD-1) in this animal model, being consistent with its reduction of triglyceride (TG) levels.

These results demonstrate that PCE reduces oxidative stress, and prevent lipid accumulation in the liver of fructose-fed rats possibly by targeting the Keap1/Nrf2 pathway. PCE may be a promising therapeutic strategy for fructose-associated liver lipid accumulation.