Physicochemical characterization and toxicity of decursin and their derivatives from Angelica gigas.
Angelica gigas NAKAI is used to treat dysmenorrhea, amenorrhea, menopause, abdominal pain, injuries, migraine, and arthritis. The present study provided a physicochemical and toxicological characterization of compounds in A. gigas NAKAI (decursin, decursinol angelate, diketone decursin, ether decursin, epoxide decursin and oxim decursin). Diketone decursin (173.16 μg/mL) and epoxide decursin (122.12 μg/mL) exhibited >100 μg/mL kinetic solubility after applying nephelometry, suggesting a highly soluble compound. The Student’s t-test revealed significant differences in the pKa ranges of the compounds by automatic titration from capillary electrophoresis (p<0.05). Diketone decursin, epoxide decursin and oxim decursin might be formulated into an oral dosage form (log P: 0-3) by an automatic titration analysis. A parallel artificial membrane permeability assay demonstrated permeability coefficients of <10 x 10⁻⁶ cm/s for all of the compounds, suggesting poor permeability. Ether decursin exhibited a toxic effect after being applied to mouse (NIH 3T3, EC₅₀: 57.9 μM) and human (HT-29, EC₅₀: 36.1 μM; Hep-G2, EC₅₀: 4.92 μM) cells. Additionally, epoxide and oxim decursin were toxic through acute oral toxicity (four and three deaths of Institute of Cancer Research (ICR) mice) and mutation toxicity testing by applying Salmonella typhimurium cells with and without S9. Although diketone decursin exhibited less permeability, it is potentially valuable pharmacological compound that should be investigated.
College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
Bimit
B
Mahat
Jung-Woo
JW
Chae
In-Hwan
IH
Baek
Gyu-Yong
GY
Song
Jin-Sook
JS
Song
Seong-Kwon
SK
Cho
Kwang-Il
KI
Kwon
D029969:Angelica / Q000737:chemistry*; D000818:Animals; D001578:Benzopyrans / Q000633:toxicity*; D002087:Butyrates / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009152:Mutagenicity Tests; D041681:NIH 3T3 Cells; D010539:Permeability; D010936:Plant Extracts / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D001578:Benzopyrans; D002087:Butyrates; D010936:Plant Extracts; C101278:decursin