Gymnemic acids

FLUORINECOMPOUNDS,ORGANIC - FLUORINATED ALIPfiATIC COMPOUNDS] (Vol 11) Gymnemic acid [122168-40-5]... 

Several natural products, eg, gymnemic acid [122168-40-5] and 2i2iphin [73667-51-3] have also shown sweet-inhibiting activities. These are not allowed for foods in the United States, however. 

It has been proposed " that the mechanism(s) of action of gymnemic acids and ziziphins is a biphasic, model-membrane penetration-process. The model suggested that the modifier molecules interact first with the receptor-cell plasma-membrane surface. It was postulated that this initial interaction involves a selective effect on taste perception, including the transduction and quality specification of the sweet stimuli, and selective depression of sweetness perception. Following the initial interaction, the modifier molecules interact with the membrane-lipid interior to produce a general disruption of membrane function and a nonselective effect on taste... 

Some compounds such as gymnemic acid from Gymnema sylvestre (Asclepiadaceae) (which depresses the preceived sweetness of sugars) are known to distort the taste of others ( ) and may play a role in "disguising" the presence of kairomones or nutritional substances. 

Nakamura, Y., Tsumura, Y., Tonogai, Y., and Shibata, T. 1999. Fecal steroid excretion is increased in rats by oral administration of gymnemic acids contained in Gymnema syhestre leaves. J. Nutr. 

H. M. Lui, F. Kiuchi, and Y. Tsuda, Isolation and structure elucidation of gymnemic acids, antisweet principles of Gymnema sylvestre, Chem. Pharm. Bull. (Tokio), 40 (1992) 1366-1375. 

The leaves of the tropical plant Gymnema sylvestre, when chewed, suppress the ability to taste sweetness. The effect lasts for hours, and sugar seems like sand in the mouth. The ability to taste other sweeteners such as saccharin is equally suppressed. There is also a decrease in the ability to taste bitterness. The active principle of leaves has been named gymnemic acid and has been found (Stocklin et al. 1967) to consist of four components, designated as gymnemic acids, Ab A2, A3, and A4. These are D-glucuronides of acety-... 

The sweetness-inhibiting substance ziziphin was isolated from the leaves of the plant Zizyphus jujuba (Rhamnaceae), which is native to China, by Kurihara et al 1 Like gymnemic acids, ziziphin is a glycoside of triterpene that suppresses sweetness in humans. Removal of the acyl group under mild hydrolytic conditions led to complete abolishment of its antisweet activity. 

Gastric inhibitory peptide acts via a GPCR on pancreatic (1 cells to promote insulin secretion. The plant natural products gymnemic acid and phloridzin inhibit D-glucose binding to the GI glucose receptor involved in glucose-stimulated GIP secretion. 

Gymnemic acid I Gymnema sylvestre (Asclepiadaceae) [leaf] Sweet-taste blockers... 

Gymnemic acid Gymnema sylvestre (Asclepiadaceae) 4- Glc absorption (4 Glc-... 

There are only a few sweetness inhibitors known. This article will focus on three sodium dodecyl sulfate (SDS), the gymnemic acids (GA) and the ziziphins (ZJ). Each of these substances has the ability to diminish or eliminate the ability to recognize sweetness. The intensity and duration of the effect varies with the inhibitor. 

A substance isolated from the Indian shrub Gymnema sylvestre, has a profound ability to reduce perceived sweetness of sugar solutions. The effect was noticed over a century ago when two British inhabitants of an Indian village found that, after chewing the leaves of G sylvestre, the sweetness of their tea disappeared (7). The sweetness suppressing activity is due to a mixture of several triterpene saponins which have collectively been termed the gymnemic acids. For most people exposed to the effects of GA, sweetness suppression is complete and the effect lasts for about an hour. 

Once a purified gymnemic acid became available, much psychophysical work was done to understand the nature of the sweetness inhibition effect. The work of Bartoshuk and co-workers illustrates the course taken (15). The results of a typical experiment are shown in Figure 3. The sweetness of a sucrose solution was almost completely suppressed after holding a gymnemic acid solution in the mouth for a few seconds. Further experiments were carried out to determine the effect of gymnemic acid on the other taste qualities (sour, bitter and salty). No effect of gymnemic acid on these tastes was observed. Early work with GA extracts had produced an apparent inhibition of bitter taste, but this effect was later attributed to cross-adaptation to the taste of the crude leaf extract, which was itself quite bitter. Experiments with refined (and tasteless) extracts showed no bitterness suppression. 

Figure 2. Structure of gymnemic acid A, (III), the most abundant gymnemic acid.

Sodium dodecyl sulfate, the gymnemic acids and the ziziphins have all been termed "surface active" taste modifiers because they all possess detergent-like properties. These molecules all have a polar and a non-polar end and they are capable of penetrating the phospholipid membranes that are believed to be components of sweetness receptors. Any speculation about the mechanism of action of these substances must take into account the experimental observations concerning miraculin, monellin, and thaumatin, which were presented at the beginning of this article. Those observations suggested that transport of the modifier to the cell s interior was not occurring and the inhibition effect is manifested at the surface of the cell. 

---