Natural Product Radiance, Vol. 5(4), 2006, pp.

270-278

Article

Non-saccharide natural intense sweeteners An overview of current status

S J Surana, S B Gokhale, R A Rajmane and R B Jadhav*
Department of Pharmacognosy, R.C.Patel College of Pharmacy Shirpur, Dist. Dhule- 425 405, Maharashtra, India *Correspondent author, address, R B Jadhav c/o Dr S G Chaudhari, Plot No. 60, Pitreshwar Colony, Shirpur, Dist. Dhule 425 405 Phone: 9822948642; E-mail: ramjadhav123@yahoo.co.in Received 29 July 2005; Accepted 1March 2006

Abstract
The global consumption of herbs as medicine, nutraceuticals, food additives, cosmaceuticals, etc. is increasing rapidly. One of such area of high commercial potential is nonsaccharide sweeteners. Numerous compounds of plant origin are reported to have different degree of sweetness. In the light of limitations of currently marketed synthetic sweeteners as well as drastic reduction of high-calorific sugar consumption especially in developed countries, an area of lowcalorific, non-saccharide natural sweeteners is gaining tremendous commercial significance. However, in recent past non-saccharide natural sweeteners gone through several ups and downs, therefore, before commercialization of non-saccharide natural sweeteners for both pharmaceutical as well as food industry, it needs to undergo rigorous evaluations. The present paper is a compilation of information on non-saccharide intense natural sweeteners derived from plant metabolites. Keywords: Plant metabolites, Non-nutritive sweeteners, Natural sweeteners, Intense sweeteners. IPC code; Int. cl.7 A61 K 35/78, A23L 2/60

Introduction
Although the history of human efforts in improving food palatability way backs to time unknown, our understanding of mechanism of taste perception remains preliminary. For several years, high calorific sugars remain main source of sweetening agent. However, changing life-style and sugarrelated health problems such as obesity and dental caries and unsuitability of sugars for diabetic patients, replacement of these high calorific sugars by low calorific intense sweeteners has become necessary. Several synthetic sweeteners of low calorific value have recently been appeared in pharmaceutical and food industries, but their health hazards due 270

to harmful side-effects restrict their utility1,2. Thus, search for non-nutritive intense sweeteners remains potential area of research. This compilation is the account of the non-nutritive intense sweeteners derived from plant metabolites along with various approaches used in discovering new sources. This paper also focuses on the methodology practiced in screening and toxicity testing. Sweeteners are the compounds that interact with taste buds that evoke a characteristic response. Sweeteners, therefore, have ability to impart sweet taste by masking the taste of material in which it is added3. Sweeteners can be broadly divided into two categories, natural and synthetic (or artificial) sweeteners. Natural sweeteners can be further divided

into saccharide and non-saccharide sweeteners. Synthetic sweeteners are further divided into two groups, organic salts and inorganic substituted salts. Although each class has its own merits and demerits, present discussion is confined to the natural non-saccharide intense sweeteners and taste modifying plant metabolites. Ideally, sweeteners should be of low-calorific value, able to mask the taste at lower concentration and it should be free from harmful side effects and suitable for long-term use. It should remain stable at wide range of temperature and pH conditions. It should have quick onset of action and no lingering after taste. Sweetener should be water soluble with high dissolution rate. In addition, it should be non-hygroscopic and should give synergetic effect with other sweeteners. Therefore, in addition to other factors, commercialization of sweetener needs to qualify most of these parameters.

Plant metabolites as sweeteners

The chemical structures of molecules that confer a sweet taste are diverse and there are about 80 sweet compounds (other than monosaccharides,
Natural Product Radiance

Article
disaccharides and polyols) obtained from natural source and most of them are derived from vascular plants 4. Nonsaccharide natural sweeteners are widely distributed in diverse plant families such as Asteraceae, Marantaceae, Rutaceae, Menispermaceae, Polypodaceae, etc. Similarly, widely diverse phytoconstituent classes ranging from small molecular secondary metabolites such as flavonoids, terpenoids, steroidal saponins, coumarins, etc. to macromolecular proteins, reported to have intense sweetening property. In addition, there are certain non-sweet plant metabolites known to modify taste effects which lead to either insensitivity towards bitter or sweet taste or modifying the sour or bitter taste to sweet taste3, 5. In Tables 1 and 2 some of these sweeteners and taste modifying plant metabolites have been summarized. with bitter taste may remain unnoticed to local population. In addition, some plants having poor sweetness may also be missed altogether. Also sweet smelling plants are not that usually give sweet taste. Thus, it is necessary to consider these aspects while exploring the ethnobotanical information to avoid subsequent failure in screening program. Third approach is chemotaxonomic tracing, but several times in given genus taste may ranges from sweet-bitter-astringent and probability of success is low. Fourth approach is random screening by organoleptic tasting especially used for undocumented sweet plants. This approach is costly and difficult and needs to investigate each plant from about 2, 40,000 angiosperm species. and behaviour model are used in screening program. In former model, plant extract or enriched fraction is applied on the tongue of anaesthetized gerbil and electrophysiological response recorded from chorda typhani nerve. In this assay, about 25 samples can be investigated in individual animal. This study is further supplemented by conditioned-taste dislike assay using gerbils that are trained to avoid sucrose. Although combination of these two models is not ideal for evaluation of human sweet taste, about 60-70 % of pure compound tested in gerbil respond correctly.

Preliminary safety screening and sweetness evaluation

Promising plant found from any of above approach is subsequently extracted and safety screening of crude extract or fractions is undertaken. Acute toxicity is investigated in mice and mutagenicity in bacteria such as Salmonella typhimurium. After the safety assessment, comparative sweetness can be judged from threshold sensory method using panel of healthy human volunteers relative to 2% w/v sucrose. Although taste perception is subjective phenomenon and several factors such as age, hunger, mood, social environment and individual characteristic affect on it, a rough idea of sweetness intensity can be judged from this protocol. Human study is some what problematic, since the large amount of extract, fraction or pure compound is required for investigation. Therefore, in addition to human study, combination of electrophysiological and behaviour model of gerbils can be considered especially when amount of material under investigation is less. 271

Screening assay for sweetness

Currently, the chemical properties of molecules that induce sweet tastes are not well understood; this eventually leads to unavailability of reliable in vitro method for screening of sweeteners. However, recent psychophysical, electrophysiological and biochemical studies suggest that sweet taste perception for these structurally diverse compounds may involve multiple receptor types and transduction mechanisms. Several mechanisms have been proposed, including competitive inhibition of sweetener receptors, interference with channels and second messenger systems in the taste cell membrane, and nonspecific interactions with taste cell membranes 4 . This information is quite useful in development of in vitro models. However, currently two in vivo methods, electrophysiological

Strategies for discovering new sweeteners from plants

Approaches similar to the drug discovery program have been practiced in discovering new sweeteners from plants 3,5,6. However, some specific clues and simplicity of taste perception are an added advantage in this case. Ethnobotanical information derived from literature and from field investigation can be a rational way in searching new sweeteners. This can be attempted by survey of local population and survey of ethnobotanical information. In former approach, interview with local communities, herbalist and traditional healers gives an idea about sweet plants. However, the information from above sources is not sole mean and many plants
Vol 5(4) July-August 2006