Fatty acid synthase inhibitors separated from oiltea camellia by high-speed counter-current chromatography

The inhibitory effects of oiltea camellia extracts (OCEs) and its active components on fatty acid synthase (FAS) were investigated. OCE potently inhibited the activity of FAS with an half-maximal inhibitory concentration (IC₅₀) value of 2.30 μg/mL. The inhibition kinetic results showed that OCE and acetyl-CoA competitively inhibited FAS but these compounds exhibited mixed inhibition against malonyl-CoA and NADPH. Further study uncovered that the active components of OCE, ellagic acid (EA) and 3-O-methylellagic acid 4'-O-β-D-glucopyranoside (MEAG), which were isolated and purified by high-speed counter-current chromatography (HSCCC) using a 2-phase solvent system of chloroform-ethanol-water-acetic acid (4:3:2:0.01, v/v/v/v), inhibited FAS with IC₅₀ of 2.50 and 37.73 μg/mL, respectively. Their inhibition kinetics were different from that of OCE. Both of them exhibited uncompetitive inhibition for nicotinamide adenine dinucleotide phosphate (NADPH) and decreased the FAS activity through inactivation of acetyl/malonyl transferase on FAS. These results suggest that OCE could be a valuable resource for bioactive substances.

With the gradual increase in tea oil production, it was in urgent need of dealing with Camellia fruit hull, which was always discarded because of low economic benefits. Camellia fruit hull has been shown to have significant antioxidant effects including 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging ability and ferric-reducing antioxidant power. This study found that the ethanolic extract of Camellia fruit hull at low concentration efficiently inhibited FAS activity, which is a potential therapy target of both obesity and cancer. These results suggest that OCE could be a valuable resource for bioactive substances.