Sucrose is generally regarded as the major cause of dental caries in western countries, because of its ubiquity in the diet. There are currently only three substances approved for use in the United States as high-intensity (non-nutritive) sweeteners, namely, saccharin and aspartame, and acesulfame K, which are used in place of sucrose in foods, beverages, and medicines. However, because questions have been raised in both the scientific literature and the popular press about the safety or sweetness quality of these substances, there is an intensive search being conducted to discover new noncariogenic and noncaloric sucrose substitutes. The plant kingdom has already afforded a number of intense sweeteners of commercial significance, such as thaumatin, stevioside, and glycyrrhizin. The objective of this investigation, therefore, is to isolate novel potentially noncariogenic natural intense sweetening agents from several plant species already identified as being sweet, as well as from other sweet plants that will be procured during the project on the basis of literature reports and observations in the field. Plant extracts and chromatographic fractions will be monitored for sweetness using previously established gerbil electrophysiological and behavioral bioassays. Pure isolates suspected as being sweet as a result of observations in the gerbil will be tested for mutagenicity and for acute toxicity in mice. Compounds deemed nonmutagenic and nontoxic will then be assessed for sweetness by a small number of human volunteers. The structures of sweet isolates will be determined by spectroscopic and chemical methods. It is hoped that at least one new sweetener to be obtained in this project may ultimately have use as a safe noncariogenic and non-nutritive sweetening agent. Alternatively, certain compounds may serve as prototype molecules for the synthesis of sweeter or more pleasant-tasting analogues. The discovery of novel sweet compounds of natural origin should also increase existing knowledge on structure-sweetness relationships, and be of use in investigations designed to rationally design sweet molecules.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE008937-01A2
Application #
3222766
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1991-04-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Pharmacy
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Kinghorn, A Douglas; Pan, Li; Fletcher, Joshua N et al. (2011) The relevance of higher plants in lead compound discovery programs. J Nat Prod 74:1539-55
Kinghorn, A D; Ito, A; Kennelly, E J et al. (1998) Studies on some edible and medicinal plants of Mesoamerica. Proc West Pharmacol Soc 41:253-8
Kinghorn, A D; Kaneda, N; Baek, N I et al. (1998) Noncariogenic intense natural sweeteners. Med Res Rev 18:347-60
Imaoka, K; Miller, C J; Kubota, M et al. (1998) Nasal immunization of nonhuman primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces Th1/Th2 help for virus-specific immune responses in reproductive tissues. J Immunol 161:5952-8
Kennelly, E J; Suttisri, R; Kinghorn, A D (1996) Novel sweet-tasting saponins of the cycloartane, oleanane, secodammarane, and steroidal types. Adv Exp Med Biol 405:13-24
Baek, N I; Chung, M S; Shamon, L et al. (1993) Selligueain A, a novel highly sweet proanthocyanidin from the rhizomes of Selliguea feei. J Nat Prod 56:1532-8
Suttisri, R; Chung, M S; Kinghorn, A D et al. (1993) Periandrin V, a further sweet triterpene glycoside from Periandra dulcis. Phytochemistry 34:405-8
Mata, R; Rodriguez, V; Pereda-Miranda, R et al. (1992) Stevisalioside A, a novel bitter-tasting ent-atisene glycoside from the roots of Stevia salicifolia. J Nat Prod 55:660-6
Kaneda, N; Lee, I S; Gupta, M P et al. (1992) (+)-4 beta-hydroxyhernandulcin, a new sweet sesquiterpene from the leaves and flowers of Lippia dulcis. J Nat Prod 55:1136-41