Kalopanaxsaponin A is a Basic Saponin Structure for the Anti-Tumor Activity of Hederagenin Monodesmosides

Abstract

Hederagenin, δ-hederin {hederagenin α-L-arabinoside}, kalopanax-saponin A {hederagenin 3-O-α-L-rhamnosyl(1→2)-α-L-arabinoside}, kalopanaxsaponin I {hederagenin 3-O-β-D-xylosyl(1→3)-α-L-rhamnosyl(1→2)-α-L-arabinoside}, and sapindoside C {hederagenin 3-O-β-D-glucosyl(1→4)-β-D-xylosyl (1→3)-α-L-rhamnosyl(1→2)-α-L-arabinoside} were isolated from stem bark of Kalopanax pictus Nakai (Araliaceae). Among glycosides of hederagenin, disaccharide (kalopanaxsaponin A, commonly also called α-hederin), trisaccharide (kalopanaxsaponin I), and tetrasaccharide (sapindoside C) showed significant cytotoxicity on several types of tumor cells, while hederagenin itself exhibited only weak cytotoxicity and its monosaccharide (δ-hederin) was non-cytotoxic. From these results, it suggests that the arabinosyl moiety at C-3 blocks the activity of hederagenin and the position of the second sugar for glycoside linkage is also important for cytotoxicity. In the in vivo experiments, kalopanaxsaponin A (15 mg/kg, i.p.) apparently increased the life span of mice bearing Colon 26 and 3LL Lewis lung carcinoma, as well as cisplatin (3 mg/kg, i.p.). These results indicated that kalopanaxsaponin A has potential anti-tumor applications.

Key words

Kalopanax pictus - Araliaceae - kalopanaxsaponin A (α-hederin) - anti-tumor activity - structure-activity-relationship (SAR)

References

• 1 Quetin-Leclercq J, Elias R, Balansard G, Bassleer R, Angenot L. Cytotoxic activity of some triterpenoid saponins.  Planta Medica. 1992;  58 279-81
• 2 Lee K T, Sohn I C, Park H J, Kim D W, Jung G O, Park K Y. Essential moiety for antimutagenic and cytotoxic activity of hederagenin monodesmosides and bisdesmosides isolated from the stem bark of Kalopanax pictus .  Planta Medica. 2000;  66 329-32
• 3 Mimaki Y, Kuroda M, Asano T, Sashida Y. Triterpene saponins and lignans from the roots of Pulsatilla chinensis and their cytotoxic activity against HL-60 cells.  J. Nat. Prod.. 1999;  62 1279-83
• 4 Kim D H, Yu K W, Bae E A, Park H J, Choi J W. Metabolism of kalopanaxsaponin B and H by human intestinal bacteria and antidiabetic activity of their metabolites.  Biol. Pharm. Bull.. 1998;  21 360-5
• 5 Lee M, Hahn D R. Titerpenoidal saponins from the leaves of Kalopanax pictum var. chinense .  Arch. Pharm. Res.. 1991;  14 124-8
• 6 Ahmad V U. Att-ur-Rahman: Handbook of Natural Products Data, II. Pentacyclic triterpenoids. In: Rahman AU, editor Amsterdam; Elsevier 1994: 223-4
• 7 Kupchan S M, Uchida I, Branfman A R, Dailey R G, Fei B Y. Antileukemic principles isolated from Euphorbiaceae plants.  Science. 1976;  191 571-2
• 8 Kirmizigul S, Anil S, Rose M E. Triterpenoid saponins from Cephalaria transsylvanica .  J. Nat. Prod.. 1996;  59 415-8
• 9 Bhandari P, Gray A I, Rastogi R P. Triterpenoid saponins from Caltha palustris .  Planta Medica. 1987;  53 98-100
• 10 Choi J S, Woo W S. Triterpenoid glycosides from the roots of Patrinia scabiosaefolia .  Planta Medica. 1987;  53 62-4
• 11 Kizu H, Shimana H, Tomimori T. Studies on the constituents of Clematis species. VI. The constituents of Clematis stans Sieb. Et Zucc.  Chem. Pharm. Bull.. 1995;  43 2187-94
• 12 Majester-Savornin B, Elias R, Diaz-Lanza A M, Balansard G, Gasquet M, Delmas F. Saponins of the ivy plant, Hedera helix, and their leishmanicidic activity.  Planta Medica. 1991;  57 260-2
• 13 Kim D W, Bang K H, Rhee Y H, Lee K T, Park H J. Growth inhibitory activities of kalopanaxsaponins A and I against human pathogenic fungi.  Arch. Pharm. Res.. 1998;  21 688-91
• 14 Calabrese A L. Antiviral activity of hederin.  J. Pharm. Sci.. 1975;  64 VIII
• 15 Danloy S, Quetin-Leclercq J, Coucke P, De Pauw-Gillet M C, Elias R, Balansard G, Angenot L, Bassleer R. Effects of α-hederin, a saponin extracted from Hedera helix, on cells cultured in vitro .  Planta Medica. 1994;  60 45-9
• 16 Mba Gachou C, Laget M, Guiraud-Dauriac H, De Meo M, Elias R, Dumenil G. The protective activity of alpha-hederin against H₂O₂ genotoxicity in HepG2 cells by alkaline comet assay.  Mutat. Res.. 1999;  445 9-20
• 17 Jeong H G, Park H Y. The prevention of carbon tetrachloride-induced hepatotoxicity in mice by a α-hederin: Inhibition of cytochrome P450 2E1 expression.  Biochem. Mol. Biol. Int.. 1998;  45 163-70
• 18 Shi J Z, Liu G T. Effect of α-hederin and sapindoside B on hepatic microsomal cytochrome P-450 in mice.  Chung Kuo Li Hsueh Pao. 1996;  17 264-6
• 19 Iszard M B, Liu J, Klaassen C D. Effect of several metallothionein inducers on oxidative stress defense mechanisms in rats.  Toxicology. 1995;  104 25-33