Furocoumarins from Angelica dahurica with Hepatoprotective Activity on Tacrine-Induced Cytotoxicity in Hep G2 Cells

Abstract

Fractionation of the MeOH extract of Angelica dahurica Benth et Hook resulted in the isolation of six furocoumarins, imperatorin (1), isoimperatorin (2), (±)-byakangelicol (3), (+)-oxypeucedanin (4), (+)-byakangelicin (5), and (+)-aviprin (6). Among these, compounds 1 and 5 exhibited strong hepatoprotective activities, displaying EC₅₀ values of 36.6 ± 0.98 and 47.9 ± 4.6 μM, respectively. Compounds 3 and 4 showed moderate activities with EC₅₀ values of 112.7 ± 5.35 and 286.7 ± 6.36 μM, respectively. Silybin as a positive control showed the EC₅₀ value with 69.0 ± 3.4 μM. Comparison of hepatoprotective activities for six furocoumarins 1 - 6 suggested that oxy-substitution at the C-9 position increased the hepatoprotective activity.

References

• 1 Watkins P B, Zimmerman H J, Knapp M J, Gracon S I, Lewis K W. Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease.  Journal of the American Medical Association. 1994;  271 992-8
• 2 Grant M H, Duthie S J, Gray A G, Burke M D. Mixed function oxidase and UDP-glucuronyltransferase activities in the human Hep G2 hepatoma cell line.  Biochemical and Pharmacology. 1988;  37 4111-6
• 3 Viau C J, Curren R D, Wallace K. Cytotoxicity of tacrine and velnacrine metabolites in cultured rat, dog, and human hepatocytes.  Drug & Chemical Toxicology. 1993;  16 227-39
• 4 Kim C M, Heo M Y, Kim H P, Sin K S, Pachaly P. Pharmacological activities of water extracts of Umbelliferae plants.  Archives of Pharmacal Research. 1991;  14 87-92
• 5 Dictionary of Natural Products on C D-ROM. Version 8 : 2. London; Chapman & Hall/CRC Press 2000
• 6 Okamoto T, Yoshida S, Kobayashi T, Okabe S. Inhibition of concanavalin A-induced mice hepatitis by coumarin derivatives.  Japanese Journal of Pharmacology. 2001;  85 95-7
• 7 Matusuda H, Murakami T, Kageura T, Ninomiya K, Toguchida I, Nishida N. et al . Hepatoprotective and nitric oxide production inhibitory activities of coumarin and polyacetylene constituents from the roots of Angelica furcijuga .  Bioorganic & Medicinal Chemistry Letters. 1998;  8 2191-6
• 8 Harkar S, Razdan T K, Waight E S. Steroids, chromone and coumarins from Angelica officinalis .  Phytochemistry. 1984;  23 419-26
• 9 Ishihara K, Fukutake M, Takayuki A, Mizuhara Y, Wakui Y, Yanggisawa T. et al . Simultaneous determination of byak-angelicin and oxypeucedanin hydrate in rat plasma by column-switching high-performance liquid chromatography with ultraviolet detection.  Journal of Chromatography B. 2001;  753 309-14
• 10 Benoit G G, Naud C F, Simard M A, Astier A L. Noninterference of cytochrome P4501A2 in the cytotoxicity of tacrine using genetically engineered V79 Chinese hamster cells for stable expression of the human or rat isoform and two human hepatocyte cell lines.  Chemical Pharmacology. 1997;  53 423-7
• 11 Colombain M, Goll V, Muyard F, Girard C, Bévalot F, Richert L. A bioassay using the human hepatoblastoma cell line HepG2 for detecting phototoxicity of furocoumarins.  Planta Medica. 2001;  67 644-6
• 12 Cho H, Jun J Y, Song E K, Kang K H, Baek H Y, Ko Y S, Kim Y C. Bakuchiol: A hepatoprotective compound of Psoralea corylifolia on tacrine-induced cytotoxicity in Hep G2 cells.  Planta Medica. 2001;  67 750-1