In Vitro Inhibition of [³ H]-Angiotensin II Binding on the Human AT₁ Receptor by Proanthocyanidins from Guazuma ulmifolia Bark

Abstract

A bioassay-guided fractionation of the 70 % acetone extract of the bark of Guazuma ulmifolia Lam. on the inhibition of angiotensin II binding to the AT₁ receptor led to the isolation and identification of bioactive oligomeric and polymeric proanthocyanidins consisting mainly of (-)-epicatechin units. The displacement of [³ H]-angiotensin II binding was dose-dependent and correlated with the degree of polymerization of the different fractions containing proanthocyanidins. A strong displacement was seen for the residual fraction suggesting that the most active substances corresponding to the highly polymerized proanthocyanidins. Angiotensin II AT₁ receptor binding might be considered as a potentially interesting biological activity of proanthocyanidins contributing to the very broad spectrum of biological activities of the condensed tannins.

Key words

Proanthocyanidins - AT₁ receptor - CHO cells - Guazuma ulmifolia - Sterculiaceae - radioligand-binding

• 1 Caballero-George C, Vanderheyden P ML, Solis P N, Pieters L, Shahat A A, Gupta M P, Vauquelin G, Vlietinck A J. Biological screening of selected medicinal Panamanian plants by radioligand-binding techniques.  Phytomedicine. 2001;  8 59-70
• 2 Dominguez X, Alcorn J. Screening of medicinal plants used by Huastec Mayans of northeastern Mexico.  Journal of Ethnopharmacology. 1985;  13 139-56
• 3 Hör M, Heinrich M, Rimpler H. Proanthocyanidin polymers with antisecretory activity and proanthocyanidin oligomers from Guazuma ulmifolia bark.  Phytochemistry. 1996;  42 109-19
• 4 Meunier M T, Villie F, Jonadet M, Bastide J, Bastide P. Inhibition of angiotensin I converting enzyme by flavanolic compounds: in vitro and in vivo studies. Planta Medica 1987: 12-5
• 5 Balde A, Van Hoof L, Pieters L, Vanden Berghe D, Vlietinck A. Plant antiviral agents. VII. Antiviral and antibacterial proanthocyanidins from the bark of Pavetta owariensis .  Phytotherapy research. 1990;  4 182-8
• 6 De Bruyne T, Pieters L, Witvrouw M, De Clercq E, Vanden Berghe D, Vlietinck A. Biological evaluation of proanthocyanidin dimers and related polyphenols.  Journal of Natural Products. 1999;  62 954-8
• 7 Ubillas R, Jolad S, Bruening R, Kernan M, King S, Sesin D, Barrett M, Stoddart C, Flaster T, Kuo J, Ayala F, Meza E, Castanel M, McMeekin D, Rozhon E, Tempesta M, Barnard D, Huffman J, Smee D, Sidwell R, Soike K, Brazier A, Safrin S, Orlando R, Kenny P, Berova N, Nakanishi K. SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago).  Phytomedicine. 1994;  1 77-106
• 8 Shahat A, Ismail S, Hammouda F, Azzam S, Lemiere G, De Bruyne T, De Swaef S, Pieters L, Vlietinck A. Anti-HIV activity of flavonoids and proanthocyanidins from Crataegus sinaica .  Phytomedicine. 1998;  5 33-6
• 9 Shahat A, Hammouda F, Ismail S, Azzam S, De Bruyne T, Lasure A, Van Poel B, Pieters L, Vlietinck A. Anti-complementary activity of Crataegus sinaica .  Planta Medica. 1996;  62 0-3
• 10 Ezaki N, Kato M, Takizawa N, Morimoto S, Nonaka G, Nishioka I. Pharmacological studies on Linderae umbellatae ramus, IV. Effects of condensed tannin related compounds on peptic activity and stress-induced gastric lessions in Mice.  Planta Medica. 1985;  1 34-8
• 11 Bahorun T, Trotin F, Pommery J, Vasseur J, Pinkas M. Antioxidant activities of Crataegus monogyna extracts.  Planta Medica. 1994;  60 323-8
• 12 Cheng J, Hsu F, Chen H. Antihypertensive principles from the leaves of Melastoma candidum .  Planta Medica. 1993;  59 405-7
• 13 Sanz M, Terencio M, Paya M. Isolation and hypotensive activity of a polymeric procyanidin fraction from Pistacia lentiscus L.  Pharmazie. 1992;  47 466-7
• 14 Dauer A, Metzner P, Schimmer O. Proanthocyanidins from the bark of Hamamelis virginiana exhibit antimutagenic properties against nitroaromatic compounds.  Planta Medica. 1998;  64 324-7
• 15 Zhu M, Phillipson D, Greengrass P, Bowery N, Cai Y. Plant polyphenols: biologically active compounds of non-selective binders to protein?.  Phytochemistry. 1997;  44 441-7
• 16 De Bruyne T. Two-dimensional NMR investigation and biological evaluation of dimeric proanthocyanidins and related polyphenols. Ph. D. Thesis, University of Antwerp (UIA) Antwerp, Belgium; 1995
• 17 Vanderheyden P ML, Fierens F LP, De Backer J P, Fraeyman N, Vauquelin G. Distinction between surmountable and insurmountable selective hAT₁ receptor antagonists by use of CHO-K₁ cells expressing human angiotensin II hAT₁ receptors.  British Journal of Pharmacology. 1999;  126 1057-65
• 18 Timmermans P B, Benfield P, Chiu A T, Herblin W F, Wong P C. Angiotensin II receptors and functional correlates.  American Journal of Hypertension. 1992;  5 221-35
• 19 Vanderheyden P ML, Verheijen I, Fierens F LP, De Backer J P, Vauquelin G. Inhibition of angiotensin II induced inositol phosphate production in CHO cells expressing human AT₁ receptors by triacid nonpeptide antagonists.  Pharmaceutical Research. 2000;  17 1482-8
• 20 Cheng Y C, Prusoff W H. Relationship between the inhibition constant (K_i) and the concentration of inhibitor which causes 50 percent inhibition (I₅₀) of an enzymatic reaction.  Biochemical Pharmacology. 1973;  22 3099-108
• 21 Hatano T, Yasuhara T, Yoshihara R, Agata I, Noro T, Okuda T. Effects of interaction of tannins with co-existing substances.VII. Inhibitory effects of tannins and related polyphenols on xanthine oxidase.  Chemical Pharmaceutical Bulletin. 1990;  38 224-9
• 22 Hagerman A. Chemistry of tannin-protein complexation.  In: Chemistry and Significance of Condensed Tannins. Plenum Press New York; 1989: 323-33
• 23 Luck G, Liao H, Murray N, Grimmer H, Warminski E, Williamson M, Lilley T, Haslam E. Polyphenols, astringency and proline-rich proteins.  Phytochemistry. 1994;  37 357-71
• 24 Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols.  The Journal of Nutrition. 2000;  130 2073-85