Extract of camellia seed cake ameliorates glycolipid metabolism disorder in mice through inhibiting ACOX1 activity

Acyl-CoA oxidase 1 (ACOX1) plays a key role in glycolipid metabolism disorders. Camellia seed cake, a byproduct of oil production, was identified as a source of ACOX1 inhibitors. Under optimized conditions (58 % ethanol, 70 °C, 62 min), the extract exhibited an 83.55 % inhibition rate and an IC₅₀ of 18.88 mg/mL after purification. Among 138 compounds identified in the extract, 57 were flavonoids, with luteolin-4'-<i>O</i>-glucoside showing the highest binding affinity to ACOX1. In diabetic mice, the extract significantly reduced hepatic ACOX1 activity by 46.49 % and blood glucose levels by 25.76 %, and simultaneously decreased blood lipids and alleviated hepatic lipid accumulation. Oxidative stress was mitigated through reduced H₂O₂ production and enhanced antioxidant enzyme activity. Furthermore, ACOX1 inhibition lowered the hepatic NADH/NAD⁺ ratio by 34.96 %, thereby upregulating SIRT1 expression by 20.00 % and suppressing UCP2 by 33.04 %, ultimately increasing ATP levels by 14.66 %. Collectively, camellia seed cake extract ameliorates glycolipid metabolism disorders via ACOX1 inhibition.