Efficient extraction and isolation of skimmianine from New Caledonian plant Medicosma leratii and evaluation of its effects on apoptosis, necrosis, and autophagy

This study was aimed at improving the current knowledge about the new Caledonian plant species Medicosma leratii, by developing efficient methods of extraction and isolation of specialized metabolites. Ultrasound-assisted extraction (UAE) significantly gave higher yields of the furoquinoline alkaloid skimmianine (22.34 mg/100 g) than accelerated solvent extraction (ASE, 1.37-12.36 mg/100 g). High-performance countercurrent chromatographic (HPCCC) separation of the methanol leaf extract with n-hexane-ethyl acetate-methanol-water (6:5:6:5 v/v) afforded skimmianine (1, 7.55 mg, HPLC-DAD purity 99.4%), normelicopidine (3, 1.87 mg, 95.6%), normelicopicine (4, 2.63 mg, 97.3%) and a new furoquinoline alkaloid named sarcodifurine C (2, 1.20 mg, 95.8%). The effect of the crude extract and its main constituent, skimmianine, on apoptosis, autophagy, and necrosis induction in tumor cells has also been investigated. The crude extract and skimmianine were found to be effective apoptosis inducers in HeLa cervical cancer cell line, but not in colon cancer SW620 and HT-29 cells. Additionally, skimmianine effectively potentiated the pro-apoptotic properties of the antincancer agent sorafenib in cervical cancer cells.