Asaroidoxazines from the Roots of Asarum asaroides Induce Apoptosis in Human Neuroblastoma Cells

• Published in: Journal of natural products (Washington, D.C.) Vol. 83; no. 10; pp. 3050 - 3057
• Main Authors: Ohta, Shinji, Oshimo, Shiori, Ohta, Emi, Nehira, Tatsuo, Ômura, Hisashi, Uy, Mylene M, Ishihara, Yasuhiro
• Format: Journal Article
• Language: English
• Published: American Chemical Society and American Society of Pharmacognosy 23-10-2020
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.0c00574

Plants in the family Aristolochiaceae contain phenanthrene skeleton-containing chemical constituents that exhibit nephrotoxic, carcinogenic, mutagenic, anti-inflammatory, and cytotoxic effects. Two new phenanthrene-containing 1,2-oxazin-6-ones, designated as asaroidoxazine A (1) and asaroidoxazine B (2), and a known aristolactam, 5-methoxyaristololactam I (3), were isolated from the roots of Asarum asaroides. The structures of compounds 1 and 2 were determined using spectroscopic methods and X-ray crystallography. Treatment of SH-SY5Y human neuroblastoma cells with 1 μM of asaroidoxazine A (1) induced nuclear condensation as well as caspase-3/7 activation, indicating that this compound is a strong apoptosis inducer in neuronal cells. This is the first report of apoptosis induction by phenanthrene-containing oxazines.