Angiotensin Converting Enzyme (ACE) Inhibitory Alkaloids from Fritillaria ussuriensis

Abstract

Bioassay-guided fractionation of the BuOH-soluble extract of Fritillaria ussuriensis afforded verticinone (1), verticine (2), and peimisine (3). Purification of these compounds was achieved with the use of various chromatographic methods. The structures of the compounds were identified on the basis of MS and NMR data analysis. Compounds 1 - 3 inhibited angiotensin I converting enzyme activity in a dose-dependent manner, displaying 50 % inhibitory concentration values of 165.0 μM, 312.8 μM, 526.5 μM, respectively. The presence of these active substances may be responsible, at least in part, for the antihypertensive action of the bulbs of Fritillaria ussuriensis.

References

• 1 Ruschitzka F, Corti R, Noll G, Luscher T F. A rationale for treatment of endothelial dysfunction in hypertension.  Journal of Hypertension. 1999;  17 S25-35
• 2 Lacaille-Dubois M A, Franck U, Wagner H. Search for potential angiotensin converting enzyme (ACE)-inhibitors from plants.  Phytomedicine. 2001;  8 47-52
• 3 Choo H YP, Peak K H, Park J, Kim D H, Chung H S. Design and synthesis of α,β-unsaturated carbonyl compounds as potential ACE inhibitors.  European Journal of Medicinal Chemistry. 2000;  35 643-8
• 4 Carson P E. Rationale for the use of combination angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy in heart failure.  American Heart Journal. 2000;  140 361-6
• 5 Anderson A, Anderson H. Plants from Réunion Island with alleged antihypertensive and diuretic effects - an experimental and ethnobotanical evaluation.  Journal of Ethnopharmacology. 1997;  58 189-206
• 6 Nyman U, Joshi P, Madsen L B, Pederson T B, Pinstrup M, Rajasekharan S, George V, Pushpangadan P. Ethnomedical information and in vitro screening for angiotensin-converting enzyme inhibition of plants utilized as traditional medicines in Gujarat, Rajasthan, and Kerala (India).  Journal of Ethnopharmacology. 1998;  60 189-206
• 7 Duncan A C, Jäger A K, Johannes van S. Screening of Zulu medicinal plants for angiotensin converting enzyme (ACE) inhibitors.  Journal of Ethnopharmacology. 1999;  68 63-70
• 8 Terencio M C, Sanz M J, Paya M J. Antihypertensive action of a procyanidin glycoside from Rhamnus lycioides .  Journal of Ethnopharmacology. 1991;  31 109-14
• 9 Li S L, Lin G, Chan S W, Li P. Determination of the major isosteroidal alkaloids in bulbs of Fritillaria by high-performance liquid chromatography coupled with evaporative light scattering detection.  Journal of Chromatography A. 2001;  909 207-14
• 10 Ding K, Lin G, HO Y -P, Cheng T Y, Li P. Prederivatization and high-performance liquid chromatographic analysis of alkaloids of bulbs of Fritillaria .  Journal of Pharmaceutical Sciences. 1996;  85 1174-79
• 11 Kang D -G, Oh H, Cho D -K, Kwon E -K, Han J -H, Lee H -S. Effects of bulb of Fritillaria ussuriensis maxim. on angiotensin converting enzyme and vascular release of NO/cGMP in rats.  Journal of Ethnopharmacology. 2002;  81 49-55
• 12 Kaneko K, Tanaka M, Haruki K, Naruse N, Mitsuhashi H. ¹³C-NMR studies on the cevanine alkaloids: the application of ¹³C-NMR spectrum for structure elucidation of new alkaloids, baimonidine and isoverticine. Tetrahedron Letters 1979;: 3737-40
• 13 Kaneko K, Katsuhara T, Mitsuhashi H, Chen Y -P, Hsu H -Y, Shiro M. Isolation and structure elucidation of new alkaloids from Fritillaria delavayi Franch.  Chemical and Pharmaceutical Bulletin. 1985;  33 2614-7
• 14 Santos R A, Krieger E M, Green L J. An improved fluorometric assay of rat serum and plasma converting enzyme.  Hypertension. 1985;  7 244-52