Antiproliferative and Apoptotic Effects of Butyrolactone Lignans from Arctium lappa on Leukemic Cells

Abstract

In the course of screening for pharmacologically active substances from extracts of crude drugs used traditionally in Sino-Japanese herbal medicines, it was found that the 70 % ethanol extract from the fruits of Arctium lappa L. (Compositae) showed potent antiproliferative activity against B cell hybridoma cell, MH60. By bioassay-guided purification, a new lignan, (+)-7,8-didehydroarctigenin, together with the known lignans (-)-arctigenin and (-)-matairesinol were isolated as the active ingredients from an aqueous ethanolic extract of the fruits of A. lappa. Of these active compounds, (-)-arctigenin showed the most potent antiproliferative activity against MH60 cells (IC₅₀ : 1.0 μM), and the activity was suggested to be due to apoptosis.

References

• 1 Eich E, Perts H, Kaloga M, Schulz J, Fesen M R, Mazumder A. et al . (-)-Arctigenin as a lead structure for inhibitors of human immunodeficiency virus type-1 integrase.  J Med Chem. 1996;  39 86-95
• 2 Youssef D, Frahm A W. Constituents of the Egyptian Centaurea scoparia; III. Phenolic constituents of the aerial parts.  Planta Med. 1995;  61 570-3
• 3 Rhaman M MA, Dewick P M, Jackson D E, Lucas J A. Lignans of Forsythia intermedia .  Phytochemistry. 1990;  29 1971-80
• 4 Christensen L P, Lam J. Acetylenes and other constituents from Centaurea species.  Phytochemistry. 1991;  30 3289-92
• 5 Inagaki I, Hisada S, Nishibe S. Lignans of Trachelospermum asiaticum var. intermedium. I. Isolation and structures of arctiin, matairesinoside and tracheloside.  Chem Pharm Bull. 1972;  20 2710-8
• 6 Ozawa S, Davin L B, Lewis N G. Formation of (-)-arctigenin in Forsythia intermedia .  Phytochemistry. 1993;  32 643-52
• 7 Marco J A, Sanz-Cervera J F, Garcia-Lliso V, Susanna A, Garcia-Jacas N. Sesquiterpene lactones, lignans and aromatic esters from Cheirolophus species.  Phytochemistry. 1994;  37 1101-7
• 8 Hayashi M, Kim Y P, Takamatsu S, Enomoto A, Shinose M, Takahashi Y. et al . Madindoline, a novel inhibitor of IL-6 activity from Streptomyces sp. K93 - 0711. I. Taxonomy, fermentation, isolation and biological activities.  J Antibiot. 1996;  49 091-5
• 9 Pag B, Pag M, Noël C. A new fluorometric assay for cytotoxicity measurements in vitro .  Int J Oncol. 1993;  3 473