Review Article
`ISSN: 0974-6943
`
`Keerthi Priya et al. / Journal of Pharmacy Research 2011,4(7),2034-2039
`Available online through
`www.jpronline.info
`Natural Sweeteners : A Complete Review
`Keerthi Priya*, Dr.Vankadari Rama Mohan Gupta, Kalakoti Srikanth
`Daewoong Pharmaceutical Co. Ltd. Balanagar,Hyderabad-500 037, Andhraprdesh, India
`Received on: 12-04-2011; Revised on: 18-05-2011; Accepted on:21-06-2011
`
`ABSTRACT
`Two types of sweeteners are available: natural sweeteners of plant origin and artificial or synthetic sweeteners. Sweetening agents either evoke sweet taste or
`enhance the perception of sweet taste. Natural sweetening agents are preferred over synthetic sweetening agents since they do not have any adverse impact
`on health. Non-saccharide natural sweetening agents are low calorific, nontoxic and super sweet (100 to 10,000 times sweeter than sugar) in nature and can
`overcome the problems of sucrose and synthetic sweeteners. Natural sweeteners are useful sugar substitutes for diabetic patients. The active sweet principles
`stored in plants can be grouped under: terpenoids, steroidal saponins, dihydroisocoumarins, dihydrochalcones, proteins, polyols, volatile oils, etc. in nature.
`Common and scientific names of these sweeteners along with their properties, chemical structure of sweet principles, pharmaceutical uses have been presented
`in this paper.
`
`Key words: Natural sweetening agents, Saccharide sweeteners, Non-saccharide sweeteners. Terpenoids, Polyols
`INTRODUCTION
`Preference for sweet taste at a range of intensities is characteristic of human
`species. In the fetus, taste buds are developed by the 16th week of gestation, and
`the new born infant is able to respond favorably to sweetened solutions. Sugar
`is a natural sweetener that provides 4 calories per gram. It is acknowledged
`that excess sugar ingestion amounts to increased energy intake which, in turn,
`can lead to weight gain and chronic diseases associated with obesity and dental
`caries. Therefore, there is need for sugar substitutes, which can help reduce
`caloric intake, particularly in overweight individuals [1] The demand for new
`alternative “low calorie” sweeteners for dietetic and diabetic purposes has
`increased worldwide. As of mid-2002, over 100 plant-derived sweet com-
`pounds of 20 major structural types had been reported, and were isolated from
`more than 25 different families of green plants. Several of these highly sweet
`natural products are marketed as sweeteners or flavouring agents in some
`countries as pure compounds, compound mixtures, or refined extracts [2].
`
`3.Sugar is also employed in the coating of pills and tablets
`4.Honey plays an important role in Ayurvedic system of medicine. It is used as
`an important vehicle for many preparations
`b. Food Industry
`Sweetening agents are used to prepare jams, chocolates, sweets, ice-creams,
`cakes, candies, juices, soft-drinks, beverages, chewing-gums and many other
`food items.
`
`Classification of Natural sweetening agents
`The search for sugar substitutes from natural sources has led to the discovery
`of several substances that possess an intensely sweet taste or taste-modifying
`properties. About 150 plant materials have been found to taste sweet because
`they contain large amounts of sugars and/or Polyols or other sweet constitu-
`ents [3]. A schematic representation of the types of sweeteners and their origin
`is given below.
`
`Many synthetic sweeteners, which are widely used are proved to be carcino-
`genic and are non-nutritive. Hence demand greatly increased for natural sweet-
`ening agents, especially for non-sacchariferous sweetening agents, because
`they are highly potent, useful, safe and low-calorie sugar alternatives. Re-
`cently it was found that Himalayan forests are good sources of plants contain-
`ing non-saccharide sweetening agents.
`
`Ideal properties of sweetening agents
`Sweetening agents should have the following ideal properties
`1.
`They are required to be effective when used in small concentration.
`2.
`They must be stable at a wide range of temperature to which the
`formulations are likely to be exposed.
`Prolonged use of these agents containing preparations should not
`produce any carcinogenic effects
`They should have very low or non-calorific value.
`4.
`They should be compatible with other ingredients in formulations.
`5.
`They should not show batch to batch variations.
`6.
`They should be readily available and inexpensive.
`
`3.
`
`Uses of Natural Sweetening agents
`a. Pharmaceutical uses
`1.In pharmaceutical industries these are used in liquid, oral preparations, loz-
`enges, pills and tablets.
`2.In liquid orals sugar is used to prepare syrup base, to maintain the consis-
`tency and viscosity of the preparation and to mask the bitter taste of the drug.
`
`*Corresponding author.
`Keerthi Priya
`Research Scientist- FR&D
`Daewoong Pharmaceutical co. Ltd.
`Andhraprdesh, India- 502313.
`Tel.: + 91-9490214505
`Fax: 084582-74465
`E-mail:keerthi09@gmail.com
`
`Sweetening Agents
`
` Natural Sweetening Agents
`
` Synthetic Sweetening Agents
`
` Saccharides Sweetening Agents
`eg. Sucrose,glucose, honey etc.
`
` Non-sacharides Sweetening Agents
`.
`
`Terpenoids
`
`Steroidal saponins
`
`Proteins
`
`Dihydrochalcones
`
`Dihydroisocoumarins
`
`Voletile oils
`
`Polyols
`
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`Keerthi Priya et al. / Journal of Pharmacy Research 2011,4(7),2034-2039
`Table 1. Various sources for different natural sweetening agents
`
`Plant
`
`Family
`
`Part
`
`Sweetening Principle
`
`Chemical Class
`
`Times Sweeter
`than Sucrose
`
`Abrusosides & glycyrrhizin
`Glycyrrhizin
`Gaudichaudioside-A
`Sucrose
`trans-Cinnamaldehyde
`Neohesperidin dihydrochalcone
`Hesperidin dihydrochalcone
`Hesperidin dihydrochalcone
`Naringin dihydrochalcone
`Cyclocaryoside
`Cynarin
`Monellin
`-
`Trans-anethole
`Glycyrrhizin
`Carnosiflosides-V,VI
`Phyllodulcin
`Trans-anethole
`Hernandulcin
`trans-Anethole
`trans-Anethole
`Perillartine
`
`Triterpene glycosides
`Triterpene glycosides
`Diterpene Glycosides
`Disaccharide
`Aromatic aldehyde
`Dihydrochalcone
`Dihydrochalcone
`Dihydrochalcone
`Dihydrochalcone
`Steroidal saponins
`Protein
`Protein
`Dihydroflavonols
`Phenylpropanoid
`Triterpene glycosides
`Triterpene glycosides
`Dihydroisocoumarin
`Phenyl propanoid
`Sesquiterpene
`Phenyl propanoid
`Phenyl propanoid
`Monoterpenoid
`
`Periandrin V
`trans-anethole
`Polypodoside
`Osladin
`Pterocaryoside A&B
`Rubusoside & Sauvioside A
`Sucrose
`Glycyphyllin
`Strigin
`Steviosides
`Mogroside V
`Trilobatin
`Miraculin
`Dihydroquercetin-3-O-
`acetate 4-(methyl ether)
`Thaumatin
`
`Triterpene glycosides
`Phenyl propanoid
`Steroidal saponin glycosides
`Steroidal saponin glycosides
`Secodammaranoid saponin
`Diterpene glycosides
`Disaccharide
`Dihydrochalcone glycosides
`Steroidal saponin Glycosides
`Tricyclicditerpenoid Glycosides
`Triterpene glycosides
`Dihydrochalcone Glycosides
`Protein
`Dihydroflavonol
`
`30-100
`100
`100
`-
`50
`1000
`300
`300
`1000
`250
`-
`2500
`400
`-
`100
`-
`300-400
`-
`1000-1500
`-
`-
`400-2000
`
`100-200
`-
`600
`50-100
`50-100
`-
`-
`100-200
`-
`200-300
`250
`400-1000
`
`Abrus Precatoris
`Achras sapota
`Baccharis gaudichaudiana
`Beta vulgaris
`Cinnamomum osmophloeum
`Citrus aurantium
`Citrus limoni
`Citrus sinensis
`Citrus paradise
`Cyclocarya palirus
`Cynara scolymus
`Dioscoreophyllum Cuminsii
`Eremophila glutinosa
`Foeniculum vulgare
`Glycyrrhiza glabra
`Hemsleya carnosiflora
`Hydrangea macrophylla
`Illicium verum
`Lippia dulcis
`Myrrhis odorata
`Osmorhiza longistylis
`Perilla frutescens
`
`Periandra dulcis
`Piper marginatum
`Polypodium glycyrrhiza
`Polypodium vulgare
`Pterocarya paliurus
`Rubus suavissimus
`Saccharum officinarum
`Smilax glycyphylla
`Staurogyne mergunsis
`Stevia rebaudiana
`Siraltia grosvenorii
`Symplococos paniculata
`Synsepalum dulcifucum
`Tessaria dodoneifolia
`
`Leguminosae
`Sapotaceae
`
`Chenopodiaceae
`Lauraceae
`Rutaceae
`Rutaceae
`Rutaceae
`Rutaceae
`-
`Asteraceae
`Menispermaceae
`-
`Umbelliferae
`Leguminosae
`-
`Saxifragaceae
`Illiciceace
`Verbenaceae
`Apiaceae
`Apiaceae
`Labiatae
`
`-
`Piperaceae
`Polypodiaceae
`Polypodiaceae
`-
`Rosaceae
`Poaceae
`Liliaceae
`-
`Asteraceae
`
`Symplocaceae
`Sapotaceae
`
`Leaves,roots
`Latex and fruit
`Aerial parts
`Roots
`Leaves
`Peels of the fruits
`Peels of the fruits
`Peels of the fruits
`Peels of the fruits
`Leaves
`Leaves & flowers
`Fruit pulp
`Entire plant
`Fresh aerial Parts
`Roots and stolons
`Rhizomes
`-
`Dried fruits
`Herb
`Fresh roots
`Fresh roots
`Leaves,seeds and
`flowering tops
`Roots
`Dried leaves
`Rhizomes
`Rhizomes
`Leaves and stem
`Leaves
`Canes
`All parts
`Leaves
`Leaves
`
`Leaves
`Fruits
`Aerial parts
`
`Thamatococcus
`
`Marantaceae
`
`Aril of the fruit
`
`SACCHARIDE SWEETENING AGENTS
`
`Protein
`
`3000
`
`floral source and on the activity of invertase normally present in honey. It is
`used as Demulcent, sweetening agents and good nutrient to infant and patients.
`It is antiseptic and applied to burns and wounds. It is a common ingredient in
`several cough mixtures, Cough drops and used in the preparation of creams,
`lotions, soft drinks and candies[11, 12].
`
`Trehalose
`Trehalose, also known as mycose or tremalose, is a natural alpha-linked
`disaccharide formed by an a
`,a -1,1-glucoside bond between two a-glucose units.
`First it was introduced by H.A.L. Wiggers in 1832. He discovered it in an ergot
`of rye. In 1859 Marcellin Berthelot isolated it from trehala manna, a sub-
`stance made by weevils, and named it trehalose. Trehalose is also known as
`Mycose. It is synthesized by fungi, plants and invertebrate animals. Trehalose
`is mainly found in Trehala manna, a common constituent of fungi (Amantia
`muscaria)[13].
`
`Trehalose has a solubility and osmotic profile similar to maltose. Above 80ºC
`tehalose becomes slightly soluble in water relative to other sugars. Compared
`to other sugars, trehalose is more stable to wide ranges of pH and heat, and
`does not easily interact with protienaceous molecules. Trehalose was shown to
`be homogenously distributed throughout all dietary formulations and was stable
`when stored for 7 days at 22ºC and for 6 weeks at 4ºC [14].
`
`As an extension of its natural capability to protect biological structures,
`trehalose has been used for the preservation and protection of biologic mate-
`rials. It stabilizes bioactive soluble proteins such as monoclonal antibodies and
`enzymes for medical use. It is used to preserve blood products for transfusion
`and greatly extends shelf life of platelets. It is used to preserve embryos during
`freeze-drying where it increases viability [15].Maltose ia also a disaccharide
`made by the action of the enzyme Maltase on starch, Lactose occurs in milk
`of all mammals and is prepared pure from cows milk.
`
`Saccharide sweetening agents have high calorific values (3600-4000 cal/gm).
`These saccharide sweeteners fulfill the most worldwide requirement. But regu-
`lar use of sugar can increase prevalence of diseases like dental caries, cardio-
`vascular diseases, obesity, diabetes mellitus and micronutrient deficiency. Hence
`demand is gradually decreasing for saccharide sweeteners.
`
`Sucrose
`The sucrose, derived from Sanskrit word Sarkara, was being extracted from
`sugarcane in India, and has been identified about 6000-10,000 BC as mentioned
`in Rig and Atharva Vedas. It was introduced in non-Asiatic continents by Alexander
`the Great (c.325 BC) [4]. Sucrose is a Disaccharide sugar obtained mainly from
`the cane juice of saccharum Officinarum (Graminae) [5] and and from the roots
`of Beta Vulgaris (chenopodiaceae) [6]. Sucrose is most often prepared as a fine,
`white crystalline powder with a pleasing, sweet taste. It consists of two monosac-
`charides, a -glucose and fructose.
`
`Sucrose melts and decomposes at 186ºC to form caramel, and when combusted
`produces carbon dioxide, and water [7]. Pharmaceutically sucrose is used for
`making syrups, lozenges. It gives viscosity and consistency to fluids. Sucrose is
`ubiquitous in food preparations due to both its sweetness and its functional
`properties; it is important in the structure of many foods including biscuits and
`cookies, candy canes, ice cream, and also assists in the preservation of foods.
`The structural and chemical formula is mentioned in Figure 1.
`
`
`
`Figure 1. The structural and chemical formula of sucrose
`
`Honey
`Honey is a sugar secretion deposited in honeycombs by the bees Apis indica
`(Indian Bee), Apis mellifera, Apis dorsata (Rock Bee) and other species of Apis
`of family Apidae. Honey is the only sweetener obtained from animal source [8].
`The typical composition of honey is: moisture, 17.7%; total sugars, 76.4%;
`ash, 0.18%; and total acid (as formic acid), 0.08%. Traditionally its use in
`food has been as sweetening agent several aspects of its use indicate that
`honey also functions as food preservative [9]. Honey also contains tiny amounts
`of several compounds thought to function as antioxidants, including chrysin,
`pinobanksin, Vitamin C, catalase, and pinocembrin [10]
`
`NON-SACCHARIDE SWEETENING AGENTS
`Non saccahride sweetening agents are those, which contain substances other
`than saccharides as sweet principles. They contain Terpenoids, proteins,
`dihydrochalcones, steroidal saponins, etc as sweet principles. The non-saccharide
`Honey is essentially a solution of Leavulose (40-50%), dextrose (32-37%)
`sweeteners posses some advantages over saccharide sweeteners. They are:
`and sucrose (0.2%) in water (13-20%). The properties of sugars vary with the
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`• Non-carcinogenic.
`• Potent sweeteners (10,000 times sweeter than sucrose).
`• They have very low calorific values, hence useful for diabetic persons.
`• They do not have any effect on prevalence of diseases.
`
`
`TERPENOIDSSteviosides
`
`Times sweeter
`than sucrose
`
`Stevioside
`Dulcoside
`RebaudiosideB
`RebaudiosideA
`RebaudiosideC
`RebaudiosideD
`RebaudiosideE
`Steiobioside
`
`250-300
`50-120
`300-350
`250-450
`50-150
`250-450
`150-300
`100-125
`
`Table3.Concentrations of rebiana
`used in various products
`Product
`Range
`(mg/kg or mg/lit)
`
`Glycyrrhizin content
`
`Persian liquorice
`(G.glabra var violaceae)
`Spanish liquorice
`(G.glabra var typical)
`Russian liquorice
`(G.glabra var glandulifera)
`
`7.5-13 %
`
`5-10%
`
`10%
`
`Keerthi Priya et al. / Journal of Pharmacy Research 2011,4(7),2034-2039
`ammonium chloride, alkali iodides, quinine and cascara. Moreover,various
`pharmacological activities of glycyrrhizin, including anti-inflammatory,
`immunomodulatory, anti ulcer, and anti allergy activities have been reported.
`Glycyrrhizin also has anti viral activity against various DNA and RNA viruses,
`including HIV and severe acute respiratory syndrome (SARS) associated
`coronavirus. Therefore, a large amount of liquorice and its extracts are on the
`world market as sweetening agents and medicinal materials[21].Ammoniated
`glycyrrhizin, the fully ammoniated salt of glycyrrhizic acid, is commercially
`available and has been found to be 100 times sweeter than sucrose. It is one of
`the most efficient substances known for masking bitter taste of quinine. A
`Chinese Natural medicine prepared from the dried roots of various glycyrriza
`sp. is most frequently prescribed as an important ingredient in many prepara-
`tions of traditional Chinese medicine(Kampou medicine) [45].
`Sapodilla (Acharas sapota)
`Table 4.Glycyrrhizin content in
`Acharas sapota (sapotaceae) is another
`various spices
`sweet plant, the latex fruits of which
`Source
`contain glycyrrhizin as sweet principle.
`Sapodilla is the medium-sized tree na-
`tive to Central America, but it also
`grown elsewhere in the tropics. It is best
`known source of chicle gum (the co-
`agulated latex) which is the basis for
`chewing gum manufacture [22]
`Polypodium glycyrrhiza
`Polypodoside A, a novel intensely sweet constituent of the rhizomes of
`polypodium glycyrrhiza. This compound was rated by human taste panel as
`exhibiting 600 times sweetness intensity of 6% w/v aqueous sucrose solution
`[23].
`Abrusosides
`These are Triterpene glycoside
`sweet principles present in the leaves
`of Indian liquorice plant Abrus
`precatorius (leguminosae). Like
`liquorice, roots of this plant also
`contain
`glycyrrhizin. Abrus
`precatorius is a climbing shrub,
`indigenously found
`throughout
`India. The plant is propagated
`through seeds. Leaves and roots of
`this plant contain sweet tasting
`Triterpene glycoside principles.
`Leaves taste sweeter than roots,
`seeds are poisonous and contain
`Abrin, a poisonous substance.
`Leaves contain Triterpene glycosides Abrusosides, A, B, C, D and E. Roots
`contain the sweet oleanane type Triterpene glycoside glycyrrhizin. Hence
`this plant is used as substitute for liquorice. Abrusosides are non-toxic.Abrisosides
`A, B, C and D are found to be 30, 100, 50, 75 times sweeter than 2% w/v
`sucrose, respectively. Abrusoside E is marginally sweet but the monomethyl
`ester proved to be more potently sweet [24, 25]. Leaf extract (purified abrusosides
`A-D) is commercially used for sweetening foods, beverages and medicines.
`Leaves, roots and seed are used for medicinal purposes [26].
`
`Steviosides
`Stevia is the safest Natural Sweetener and it can substitute sucrose in various
`preparations and formulations.[16] Steviosides are obtained from leaves of small
`perennial herb Stevia Rebaudiana
`Table2. Components of Stevia
`(compositae),a native of Paraguay, South
`rebaudiana leaf
`Brazil and cultivated in Japan, southeast
`Asia, USA, etc. Stevioside was first iso-
`Component
`lated principle of this plant, which is 200-
`300 times sweeter principle than sucrose.
`In addition to stevioside several other sweet
`principles such as steviosides A and B,
`Steviobioside, RebaudiosideA, B, C, D, E
`and Dulcoside A were isolated from Stevia
`rebaudiana leaf. The major components
`of the leaf and their sweetness potency
`are shown in the table 2 [17].
`Stevioside is the major component (5-15% in the dried leaves) of sweet tasting
`leaf extract but has an unpleasant after taste, this problem is solved by blending
`it with other compounds or by its conversion into RebaudiosideA, which is
`normally present in the leaves in lower content (3-4%), does not have any after
`taste and has a sweetening power 1.2 to 1.6 times higher than steviosides.
`Rebiana
`Rebiana is the common name for
`highly-purity rebaudiosideA. It is
`sweeter and more delicious than
`stevioside [18]. It provides Zero calo-
`ries and has a clean, sweet taste with
`50-600
`Carbonated soft drinks
`no significant undesirable taste char-
`50-600
`Still beverages
`acteristics. It is also well suited for
`200-200
`Powdered soft drinks
`300-6000
`Chewing gum
`blending with other non-caloric or
`150-1000
`Dairy products
`carbohydrate sweeteners. Rebaudioside
`200-1000
`Edible gels
`is often 200-300 times sweeter than
`200-1000
`Nutraceuticles
`50-1000
`Pharmaceuticals
`that of sucrose. As a dry powder
`rebiana is stable for at least 2 years at ambient temperature and under con-
`trolled humidity conditions. In solution, it is most stable between pH values 4-
`8 noticeably less stable below pH 2. Stability decreases with increase in tem-
`perature [19]. Typical rebiana concentrations used to sweeten various foods and
`beverages and pharmaceuticals are shown in the table 3. Marketed products are
`also available. There is no report on toxicity of Stevia glycosides. In Japan
`Stevia sweeteners are used in wide range, in liquid or solid foods, beverages as
`a substitute for conventional sugars or artificial diethetics, at present more
`than 10 food industries in Japan are undertaking the production of Stevia
`glycosides as food additives [20].
`
`Glycyrrhizin
`Glycyrrhizin is a pentacyclic triterpenoid saponins glycoside obtained from
`the root and stolons of the plant Glycyrrhiza glabra (Leguminosae) com-
`monly known as liquorice. Other species of Glycyrrhiza like G.foetida, G.inflata
`also contain this sweet principle. Liquorice plant is native of Mediterranean
`region and China, cultivated in France, Italy, Spain, USSR, USA, England and
`Asia. In India it is found in Srinagar, Jammu, Dehradun, Baramulla, temperate
`Himalayan regions and south hilly
`districts. It is propagated through
`division of crown or rooted cut-
`tings
`of
`underground
`stem.Glycyrrhizin is found in the
`form of potassium and calcium salt
`of glycyrrhizic acid (a trihydroxy
`acid, C42H62O; mp 205ºC quick de-
`compose) in the roots and stolons
`of liquorice plant. Different vari-
`eties of liquorice contain varying
`amounts of glycyrrhizin (from 6-
`Fig. Liquorice root
`14%)[24]. Because of its sweet taste,
`glycyrrhizin is used worldwide as a
`natural sweetener and flavouring additive. It has been used as expectorant in
`cough mixtures and as flavouring agent in formulations of nauseous drugs like
`a b c
`Journal of Pharmacy Research Vol.4.Issue 7. July 2011
`
`Table 5. The botanical name, chemical structure, potency of terpenoid
`sweeteners
`Botanical name
`and family
`
`Active sweet
`principle
`
`Chemical
`structure
`
`Sweetness
`compared
`to sucrose
`
`Native place
`of plant species
`
`Perrilla frutescens L
`(Labitae)
`
`Monoterpenoid
`(Perillartine)
`
`Stevia rebaudiana Bertoni Diterpenoid
`(compositae)
`(stevioside)
`
`Glycyrrhiza glabra
`(Leguminosae)
`
`Abrus precatorius
`(Leguminosae)
`Achras sapota
`(Sapotaceae)
`
`Triterpenoid
`(Glycyrrhizin)
`
`Triterpenoid
`(Glycyrrhizin)
`Triterpenoid
`(Glycyrrhizin)
`
`
`a
`
`b
`
`c
`
`-do-
`
`-do-
`
`400-2000
`
`India
`Sino-Japan
`Southeast Asia
`
`200-300
`
`Paraguay and
`
`South Brazil
`Mediterranean
`
`Countries & China
`India
`
`S.America
`
`100
`
`
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`Perillartine
`Perillartine is a monoterpene volatile oil obtained from the leaves, seeds and
`flowering tops of the plant perilla frutescens (Labitae).This plant is indigenous
`to India and found in Japan and Southeast Asia. Perllartine is 400-2000 times
`sweeter than sucrose on a unit weight basis, and 4-8 times sweeter than
`saccharine. The volatile oil provides flavours to sauces and confectionary as it
`contains the super sweet principle Perillartine [27].
`
`Keerthi Priya et al. / Journal of Pharmacy Research 2011,4(7),2034-2039
`Monellin
`Monellin is present in red berries of West African plant Dioscoreophyllum
`cumminsii Diels. This protein is about 3000 times sweeter than sucrose on a
`weight basis. Unlike the single chain thaumatin, monellin consists of two
`polypeptides of 45 and 50 amino acid residues, respectively that are associ-
`ated through non-covalent interactions. Monellin has been shown to lose its
`sweetness when heated above 50ºC under acidic pH [28].
`
`DIHYDRO ISOCOUMARINS
`
`Phyllodulcin
`Phyllodulcin is obtained from the plant Hydrangea macrophylla (Saxifragaceae)
`commonly known as amacha. This plant is Indigenous to Japan, china and is
`found in North and south America, an d temperate hills of India particularly
`Assam and in Himalayas. The sweet principle, is 300-400 times sweeter than
`sucrose, is shown in table 6. [4]
`Table 6. Source, family, chemical structure active principles of
`Phyllodulcin
`
`Botanical name
`And family
`
`Active sweet
`principle
`
`Chemical
`structure
`
`Sweetness
`compared to sucrose
`
`Native place
`of plant species
`
`300-400
`
`Japan, china,
`North & South
`America and India
`
`Hydrangea
`macrophylla
`(Saxifragaceae)
`
`
`Dihydro
`Isocoumarin
`(phyllodulcin)
`
`a
`
`a
`PROTEIN SWEETENERS
`
`Thaumatin
`The Thaumatins are a family of very sweet proteins present in the fruits of
`the tropical plant Thaumatococcus danielli (marantaceae) a bushy plant that
`grows in west Africa[28] All the forms of a Thaumatin are intensely sweet, and
`have 207 amino acids. The two predominant forms, Thaumatin I and II differ
`by 5 amino acids.Thaumatin elicits a very sweet taste that is rated to be 2000
`to 10000 times sweeter than sucrose, depending on purity and concentration.
`Thaumatin I and II are soluble in water and dilute alcohol [29]. Their solubility
`is maximal at pH 2.7-3. The sweetening power does not disappear on heating.
`The sweetness of Thaumatin disappeared on heating at pH above 7 for 15
`min, but the sweetness remained even after heating at 80ºC for 4 hr at pH 2.
`This indicated that the protein Thaumatin is more thermoresistent under acid
`conditions than under neutral or alkaline conditions [30] Thaumatin is effective
`at masking bitter notes often associated with pharmaceuticals or vitamins.
`Used at 20-400 ppm in pills and tablets, its long lasting effect covers strongly
`bitter aftertastes and leaves a pleasant feeling in the mouth. Thaumatin can
`also be useful for masking astringency and off-flavors [31]
`
`Miraculin
`The taste- modifying protein, miraculin has the unusual property of being able
`to modify a sour taste into a sweet taste [32]. Richardella dulcifica (sapotaceae),
`a shrub native to tropical West Africa, produces red berries that have an active
`ingredient, glycoprotein molecule with some trailing carbohydrate chains called,
`miraculin, a taste modifying protein that cause citric acid, ascorbic acid, and
`acetic acid, which are normally sour, to perceived as sweet after the berry has
`been held in the mouth[32] The maximum sweetness after exposure to 0.4 µm
`miraculin induced by 0.02M citric acid was estimated to be around 400000
`times that of sucrose on a molar basis [32, 33] The taste modifying effect lasts for
`usually 1-2 hr. Miracle fruit is available as freeze dried granules or in tablets –
`this form has a longer shelf life than fresh fruit. Tablets are made from
`compressed freeze dried fruit which causes the texture to be clearly visible
`even in tablet form [34].
`
`Curculin
` Curculin isolated from curculigo latifolia, aplant grown in Malaysia, has an
`intriguing property of modifying sour taste into sweet taste. In addition to this
`taste modifying activity, curculin itself elicits a sweet taste [28] Curculin has a
`unique property to exhibit both taste modifying activities. Although curculin
`was originally reported to be a homodermic protein, sweet taste of this pro-
`tein is actually expressed by its heterodermic isoform (also termed neoculin)
`composed of two homologous subunits designated as curculi1, curculin2, which
`share 77% identity in the amino acid sequences. The underlying mechanism
`for the sweet tasting and taste modifying dual capability of curculin remains
`largely a mystery [35].
`
`Mabinlin
`Mabilin the sweet tasting polypeptide exists in the fruits of Chinese plant
`capparis masaki. This protein is comprised of two polypeptide chains, of 33
`and 72 amino acids respectively, which are tightly associated through non-
`covalent interactions. It is about 100 times sweeter than sucrose on a weight
`basis [28].
`
`Pentadin
`Fruits of the plant penta diplandra brazzeana Ballion, a climbing shrub found
`in some countries of tropical Africa(such as Gabon), contain 12-kDa sweet-
`tasting protein, first isolated by van der Wel et al (1989). Electrophoretic
`studies in the presence and absence of 2-mercaptoethanol suggested that the
`mature protein consists of subunits coupled by disulfide bonds. The sweetness
`intensity was estimated to be around 500 times that of sucrose on a weight
`basis.No further work has been reported towards characterization of this sweet-
`tasting protein [36]
`
`Brazzein
`Brazzein is also contained in the fruit of P.brazzeana Ballion. It was first
`isolated by Mind and Hellekant(1994). The molecular mass of Brazzein is
`6473, and its three dimensional structure has been solved, like thaumatin,
`brazzein is a single chain protein (54 amino acids). Its sweetness profile
`remains even after incubation at 353 K for 4 hrs, probably because of its
`compact structure afforded by its four disulfide bridges [28]. Comparision of
`thaumatin, monellin, mabinlin, pentadin, brazzein, curculin and miraculin are
`shown in the table 7.
`Table 7. Composition of protein sweeteners
`Protein
`Source
`Geographic
`Sweetenes
`Distribution
`
`Sweetness factor Amino acids
`(Weight Basis)
`
`Thaumatin
`Monellin
`
`West Africa
`Thaumatococcus danielli Benth
`Dioscoreophyllum Cumminsii Diels West Africa
`
`Mabinlin
`
`Pentadin
`Brazzein
`Curculin
`Miraculin
`
`Capparis masaki
`
`Pentadiplandra brazzeana
`Pentadiplandra brazzeana
`Curculingo latifolia
`Richadella dulcifica
`
`China
`
`West Africa
`West Africa
`Malaysia
`West Africa
`
`3,000
`3,000
`
`100
`
`500
`2000
`550
`-
`
`207
`45(A chain)
`50(B chain)
`33(A chain)
`72(B chain)
`
`54
`114
`191
`
`DIHYDROCHALCONES
`Glycyphyllin
`The sweet principle glycyphyllin is present in almost all parts of the plant
`smilax glycyphylla (liliaceae). Commonly, it is known as barichob-chini. It is
`Indigenous to India and found in Himalayas. It is mainly propagated through
`Rhizomes and tuberous roots. The sweet principle is a dihydrochalcone gluco-
`side, 100-200 times sweeter than sucrose. The extract of shoot or almost all
`parts provide sweetening agent [4].
`
`Trilobatin
`Trilobatin is obtained from the plants Symplococos paniculata (simplocaceae)
`commonly known as sweet leaf, sapphire berry, ludh. This plant is found in India
`and is being cultivated on large scale. It is 400-1000 times sweeter than sucrose.
`A water soluble fraction from the bark has been reported to exhibit antioxidative
`activity. Seeds contain oil. Leaves are used as fodder. Further studies are required
`on quantity and distribution of sweet principles in different parts of plant [4].
`
`Neohesperidin Dihydrochalcone
` Neohesperidin is obtained from the peels of the fruits of plant citrus aurantium
`(Rutaceae), commonly known as Seville orange.The flavonoid compound
`neohesperidine is itself bitter but dilute alkali extract gives a sweet compound
`called Neohesperidin dihydrochalcone, which is about 1000 times sweeter than
`sucrose and has a slow onset and persists for some time.The sweetener is rela-
`tively inert to the action of carcinogenic bacteria and is approved in Belgium for
`use as a sugar substitute in beverages and chewing gum [37].
`
`Naringin Dihydrochalcone
`The sweet principle, Naringin is a type of dihydrochalcone. The flavonoid
`Journal of Pharmacy Research Vol.4.Issue 7. July 2011
`
`2034-2039
`
` KINDERFARMS Ex. 1028
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`Keerthi Priya et al. / Journal of Pharmacy Research 2011,4(7),2034-2039
`Cyclocaryoside
`parent compound naringin is bitter present in the peels of fruit of the plant
` Three intensely sweet cyclocaryosides I, II and III are obtained from the leaves
`Citrus paradisi (Rutaceae) commonly known as grape fruit. However, the naringin
`of cyclocarya paliurus, the structure of cyclocaryoside is elucidated as 20, 24
`extract in dilute alkali gives a sweet principle, naringin dihydrochalcone, which
`epoxy- dammaran-(3ß, 12ß, 20S, 24R)-12-ß-D-quinovo pyranosyl-25-hydroxy-
`is nearly 1000 times sweeter than sucrose. The plant is indigenous to West
`3-O-a-L arabino furanoside. It is the main sweet principle of the plant, possess-
`Indies and is cultivated in India. Naringin can be commercialized and could be
`ing about250 times more than the sweetness intensity of sucrose [24].
`used to prepare neohesperidin.
`
`POLYOL SWEETENERS
`
`Hesperitin Dihydrochalcone
`The parent compound Hesperitin is isolated from the peels of the plant Citrus
`sinensis and citrus limoni (Rutaceae). The reduction of hesperidin in dilute alkali
`yields hesperidin dihydrochalcone. Partial hydrolysis of this compound, either
`by acid or by dissolved or immobilized enzyme, gives rise to sweet hesperetin
`dihydrochalcone. This is 300 times sweeter than sucrose [37, 38].Citrus sinensis is
`commonly known as betavian, sweet orange. It is native of India and China and
`cultivated widely in subtropical regions as most valued commercial citrus of the
`world. Citrus limoni is commonly known as lemon and jambira. Wild stock of
`this plant is native of Northwest region of India. Both plants are widely culti-
`vated in India [24] The botanical name, chemical structure, sweet