Stevia rebaudiana - a gift for diabetics.
KALPANA M, ANBAZHAGAN M, RAJENDRAN R,
Plant Archives, 11 (1) (2011) 1-3
Stevia rebaudiana Bertoni is a natural sweetener and the leaves of it are the sources of diterpene glycosides namely stevioside and rebaudioside which are 300 times sweeter than cane sugar. Among the stevioside and rebaudioside, stevioside stands first in the sweetener form, utilization and commercial value. In the present text, literatures about S. rebaudiana, the forms its sweetener, commercial value of S. rebaudiana and stevioside and their nutritional advantages are discussed. It is concluded that both S. rebaudiana and stevioside are very safe when they are used as sweetener. They are ideal for both diabetics and phenylketonuria (PKU) patients. They are also good for obese persons who are intending to lose weight by avoiding sugar supplements in their diets. Moreover, no allergic reactions have been reported.

The antioxidant activity and the bioactive compound content of Stevia rebaudiana water extracts.
KIM I-S, YANG M, LEE O-H, KANG S-N,
LWT - Food Science and Technology, 44 (5) (2011) 1328-1332
Stevia rebaudiana (SR), a chrysanthemum herb, has been used as a vegetable-based sweetening additive in health drinks and in other foods. This study was conducted to investigate the antioxidant activity and the bioactive compounds found in water extracts taken from SR leaves and calli. Analysis of vitamins in the leaves showed that folic acid (52.18 mg/100 g) was a major component, followed by vitamin C. The total phenolic and flavonoid contents were found to be 130.76 mg catechin and 15.64 mg quercetin for leaves and 43.99 mg catechin and 1.57 mg quercetin for cellus at mg of water extracts, respectively. Pyrogallol was the major material among the phenolic compounds in both leaf and callus extracts. Furthermore, our results showed that the leaf extracts contained higher amounts of free radicals, hydroxyl radicals and superoxide anion radical scavenging activities than those of the callus extracts.

Effect of Stevia rebaudiana Bertoni ethanolic extract on anti-cancer activity of Erlisch’s Ascites carcinoma induced mice
P RAJESH, V RAJESH KANNAN, M THAMBI DURAI,
Current Biotica, 3 (4) (2010) 549-554
Anti-cancer activity of ethanolic extract of leaves of Stevia rebaudiana was determined inthe rat by induced Erlisch’s Ascites carcinoma. At doses of 100 and 300 mg/kg/i.p., the extractinhibited proliferation of cell count significantly (P<0.01) compared with 5-Fluoro Uracil (20mg/kg/i.p), which was used as the reference standard drug. The S. rebaudiana showed itssignificance by dose dependent manner.

Stevia and sucrose effect on plaque formation.
DE SLAVUTZKY, SMB,
J. für Verbraucherschutz und Lebensmittelsicherheit, 5 (2) (2010) 213-216
An in vivo study was done by measuring the accumulation of dental plaque after rinsing with a solution of 10% sucrose four times daily during 5 days and comparing it with a rinsing of 10% solution of Stevia rebaudiana Bertoni four times a day, during 5 days a week. The accumulation of dental plaque after rinsing with Stevia was 57, 82% less than under rinsing with sucrose as measured by the Silness-Löe index and 10, 40% less plaque when measured by O’Leary index of plaque.

Stevioside and related compounds: therapeutic benefits beyond sweetness.
CHATSUDTHIPONG V, MUANPRASAT C,
Pharmacology and Therapeutics, 121 (1) (2009) 41-54
Stevioside, an abundant component of Stevia rebaudiana leaf, has become well-known for its intense sweetness (250-300 times sweeter than sucrose) and is used as a non-caloric sweetener in several countries. A number of studies have suggested that, beside sweetness, stevioside along with related compounds, which include rebaudioside A (second most abundant component of S. rebaudiana leaf), steviol and isosteviol (metabolic components of stevioside) may also offer therapeutic benefits, as they have anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions. It is of interest to note that their effects on plasma glucose level and blood pressure are only observed when these parameters are higher than normal. As steviol can interact with drug transporters, its role as a drug modulator is proposed. This review summarizes the current knowledge of the pharmacological actions, therapeutic applications, pharmacokinetics and safety of stevioside and related compounds. Although much progress has been made concerning their biological and pharmacological effects, questions regarding chemical purity and safety remain unsolved. These issues are discussed to help guide future research directions.

The neuroprotective effects of isosteviol against focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats.
XU D, DU W, ZHAO L, DAVEY AK, WANG J.
Planta Medica, 74 (8) (2008) 816-821
Occlusion of a cerebral artery impairs blood flow leading to neuronal death. Reperfusion of the tissue is associated with inflammation, increased reactive oxygen species, necrosis and apoptosis. Hence, damage to the brain will continue even after the blood flow is restored. Isosteviol has been demonstrated to have protective effects against ischemia-reperfusion (IR) injury in the rat heart and the current study was undertaken to determine whether it is also effective in preventing IR injury in the brain. Rats were divided into six groups: a sham-operation control group and 5 IR groups that were pre-treated with either isosteviol 5 mg.kg (-1), 10 mg.kg (-1), 20 mg.kg (-1), nimodipine 5 mg.kg (-1), or saline. Cerebral ischemia was induced for 2 hours. Twenty-two hours after re-perfusion the rats were assessed for neurobehavioral deficit, infarct volume, histological changes, and malondialdehyde, superoxide dismutase (SOD), Bcl-2 and NF-kappaB levels in brain tissue. Pre-treatment with isosteviol reduced infarct volume, ameliorated cell death and infiltration of neutrocytes, improved neuro-locomotor activity, increased SOD activity, induced Bcl-2, suppressed lipid superoxidation and the expression of NF-kappaB, and therefore retarded necrosis and apoptosis of neurons and inflammation. These positive effects were dose-dependent with an isosteviol dose of 20 mg.kg (-1), thus being as effective as nimodipine.

Comparative studies of the antioxidant effects of a naturally occurring resveratrol analogue - trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene and resveratrol - against oxidation and nitration of biomolecules in blood platelets.
OLAS B, WACHOWICZ B, NOWAK P, STOCHMAL A, OLESZEK W, GLOWACKI R, BALD E,
Cell Biology and Toxicology, 24 (4) (2008) 331-340
The action of two phenolic compounds isolated from the bark of Yucca schidigera: trans-3,3',5,5'-tetrahydroxy-4'- methoxystilbene and its analogue - resveratrol (trans-3,4',5-trihydroxystilbene, present also in grapes and wine) on oxidative/nitrative stress induced by peroxynitrite (ONOO(-), which is strong physiological oxidant and inflammatory mediator) in human blood platelets was compared. The trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene, like resveratrol, significantly inhibited protein carbonylation and nitration (measured by enzyme-linked immunosorbent assay method) in the blood platelets treated with peroxynitrite (0.1 mM) and markedly reduced an oxidation of thiol groups of proteins (estimated with 5,5'-dithio- bis(2-nitro-benzoic acid)] or glutathione (measured by high performance liquid chromatography method) in these cells. The trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene, like resveratrol, also caused a distinct reduction of platelet lipid peroxidation induced by peroxynitrite. The obtained results indicate that in vitro trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene and resveratrol have very similar protective effects against peroxynitrite-induced oxidative/nitrative damage to the human platelet proteins and lipids. Moreover, trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene proved to be even more potent than resveratrol in antioxidative tests. We conclude that the novel tested phenolic compound - trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene isolated from Yucca schidigera bark possessing Generally Recognized As Safe label given by the Food and Drug Administration and allows their human dietary use - seems to be a promising candidate for future evaluations of its antioxidative activity and may be a good candidate for scavenging peroxynitrite.

Novel nutraceutical compositions containing Stevia extract or stevia extract constituents and uses thereof.
FOWLER A, GORALCZYK R,
WO 2009/071277 (A1) - 2009-06-11
DSM IP ASSETS BV [NL]; FOWLER ANN [CH] 2007
The invention relates to a novel nutraceutical composition containing Stevia extract or its constituents, such as steviol and stevioside, as active ingredient(s). The term "nutraceutical" as used herein denotes usefulness in nutritional, pharmaceutical and veterinary fields of application. The compositions are useful for improvement of cognitive functions, such as learning, memory and alertness, and psychotic stability.

Stevioside Improves Pancreatic Beta-Cell Function during Glucotoxicity via Regulation of Acetyl-CoA Carboxylase.
CHEN J, JEPPESEN PB, NORDENTOFT I, HERMANSEN K,
American J. Physiology, Endocrinology and Metabolism, 292 (6) (2007) E1906-E1916
Chronic hyperglycemia is detrimental to pancreatic beta-cells, causing impaired insulin secretion and beta-cell turn over. The characteristic secretory defects are increased basal insulin secretion (BIS) and a selective loss of glucose-stimulated insulin secretion (GSIS). Several recent studies support the view that the acetyl-CoA carboxylase (ACC) plays a pivotal role for GSIS. We have shown that stevioside (SVS) enhances insulin secretion and ACC gene expression. Whether glucotoxicity influences ACC and whether this action can be counteracted by SVS are not known. To investigate this, we exposed isolated mouse islets as well as clonal INS-1E beta-cells for 48 h to 27 mM or 16.7 mM glucose, respectively. We found that 48 h exposure to high glucose impairs GSIS from mouse islets and INS-1E cells, an effect that is partly counteracted by SVS. The ACC dephosphorylation inhibitor, okadaic acid (OKA, 10-8 M), and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR, 10-4 M), an activator of 5-AMP protein kinase that phosphorylates ACC, eliminated the beneficial effect of SVS. 5-tetrade- cyloxy-2-furancarboxylic acid (TOFA), the specific ACC inhibitor, blocked the effect of SVS as well. During glucotoxity, ACC gene expression, ACC protein, and pACC protein were increased in INS-1E beta-cells. SVS pretreatment further increased ACC gene expression with strikingly elevated ACC activity and increased glucose uptake accompanied by enhanced GSIS. Our studies show that glucose is a potent stimulator of ACC and that SVS to some extents counteracts glucotoxicity via increased ACC activity. SVS possesses the potential to alleviate negative effects of glucotoxicity in beta-cells via a unique mechanism of action. Key words: mouse islets, INS-1E beta-cell line, carnitine-palmitoyl transferase 1, insulin secretion, type 2 diabetes mellitus.

The Effect of Yucca schidigera Extract on Ruminal Fermentation and Parameters Traits in Sheep.
LIU, C-L, LI, Z-Q, DU, J, SHAN, A-S,
Agricultural Sciences in China, 6 (1) (2007) 121-128
In a completely randomized block design experiment, 16 ruminally cannulated sheep (40±2.1 kg) fed a 50% concentrate: 50% forage diet (DM basis) were given intraruminal doses of powdered Yucca schidigera extract (YSE). Doses of 0 (control), 100, 200, or 300 mg kg-1 diet were given at 8 p.m. and 4 a.m. On 15, 16, and 17 d of the experimental period, ruminal contents were sampled 0, 2, 4, 6, and 8 h after dosing, and blood samples were collected at the end of the experiment (18th and 19th d). Acidity was not affected (P > 0.05) by the addition of YSE. Compared with the control, ruminal propionate concentration was increased by 29.4 and 29.8% (P > 0.05) and the acetic acid concentration was decreased by 15.1 and 19.8% (P > 0.05) at 4 and 6 h after YSE (300 mg kg-1) dosing, respectively. Ruminal ammonia concentration in the first 2 h after feeding was higher (P < 0.05) in the sheep that did not receive YSE (increased by 17.57 mg 100 mL-1) than in those that received 200 mg kg-1 (increased by 6.77 mg 100 mL-1) or 300 mg kg-1 (increased by 6.50 mg 100 mL-1) YSE. Protozoan populations in the rumen were lower (P < 0.05) in the animals that received 300 mg kg-1 of YSE compared with the control. All serum parameters of the four groups were in the normal range and were similar among the treatment groups (P > 0.05), after being fed for 19 d with different doses of YSE. The effect of YSE on ruminal ammonia concentration likely resulted from a decreased concentration of protozoan populations and, presumably, from ammonia binding by YSE.

Effect of Yucca schidigera Saponin Powder on Dry Matter Intake and Nutrient Utilization of Dry Brewers' Grains Based Concentrate Mixtures by Rams on a Basal Batiki Grass Diet.
AREGHEORE, EM, SAIPAIA, M,
World J. Agricultural Sciences, 3 (2) (2007) 224-229
Four rams (Fiji Fantastic sheep) pre-trial Body Weight (BW) of 42.8±1.4 kg and 2 years old on a basal diet of batiki grass (Ischaemum aristatum var indicum) were allotted to four dietary treatments in a randomized 4×4 Latin Square design, to investigate the effect of inclusion of Yucca schidigera Saponin Powder (YSP) in Dried Brewers’ Grains (DBG) based concentrate mixtures on dry matter intake, live-weight gain Daily Protein Intake (DPI) and nutrient digestibility. YSP was added at four different levels-0 mg, 90 mg, 120 mg and 160 mg to the concentrate mixture and four dietary treatments designated as D -0 mg YSP (Control); D -90 mg YSP; 1 2 D -120 mg YSPand D -160 mg YSP were fed to the rams. The inclusion of the YSP numerically improved the 3 4 voluntary intake of the concentrate mixtures but not at statistical significant (p>0.05) level. Voluntary intake of the forage portion was higher in rams on D4, however this was not statistically significant (p>0.05). Total Dry Matter Intake (DMI) (concentrate +forage) followed the pattern of forage intake. DMI expressed on metabolic weight basis was 234.1, 235.2, 239.1 and 244.5 g kgG W /day for D1, D2, D3 and D4, respectively. Total DMI 1 0.75 improved numerically with incremental levels of Yucca schidigera saponin powder (p>0.05). Daily Live Weight Gain (DLWG) was lower (p<0.05) in rams on D1. DLWG improved in rams on D2, D3 and D4 that had YSP included at different levels in the concentrate mixtures, however, this was not statistically significant (p>0.05). Feed Efficiency (FE) (g feed/g gain) was lower (p<0.05) in the rams on D1 than those on D2, D3 and D4. Apparent digestibility of CP improved numerically, with incremental levels of YSP in the concentrate mixtures but not at a significant level (p>0.05). Daily Protein Intake (DPI) was 9.8, 12.9, 13.6 and 14.2 (g kgG W/day) 1 0.75 for rams on D1, D2, D3 and D4, respectively. The inclusion of YSP in the DBG based concentrate mixtures at the different levels improved voluntary DMI, FE, DPI, CP digestibility and subsequently DLWG. Based on the above, it is hereby
suggested that levels higher than 160 mg used in this trial should be evaluated in DBG based concentrate mixtures for rams in further studies.

Anti-inflammatory and anti-arthritic effects of Yucca schidigera: a review.
CHEEKE, PR, PIACENTE, S, OLESZEK, W,
J. Inflammation, 3 (1) (2006) 1-7
Yucca schidigera is a medicinal plant native to Mexico. According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatory effects. The plant contains several physiologically active phytochemicals. It is a rich source of steroidal saponins, and is used commercially as a saponin source. Saponins have diverse biological effects, including anti- protozoal activity. It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa which may have a role in joint inflammation. Yucca is also a rich source of polyphenolics, including resveratrol and a number of other stilbenes (yuccaols A, B, C, D and E). These phenolics have anti-inflammatory activity. They are inhibitors of the nuclear transcription factor NFkappaB. NFkB stimulates synthesis of inducible nitric oxide synthase (iNOS), which causes formation of the inflammatory agent nitric oxide. Yucca phenolics are also anti-oxidants and free-radical scavengers, which may aid in suppressing reactive oxygen species that stimulate inflammatory responses. Based on these findings, further studies on the anti-arthritic effects of Yucca schidigera are warranted.

Isolation, identification and characterization of effective bacteria on bioremediation from the waste parts of Stevia rebaudiana Bertoni.
OKAMOTO, K, SATOU, N,
Enzyme and Microbial Technology, 39 (3) (2006) 407-413
Four thermophilic strains were isolated by thermophilic treatment (2 days at 55 °C) of the stevia-powder, and were identified by the sequence analysis of the 16S rRNA gene; Ureibacillus thermosphaericus (FERM P-20039), Bacillus thermoamylovorans-1, B. thermoamylovorans-2 and Thermoactinomyces candidus. Since all of them have nitrate-reducing and ammonium-forming ability, it is highly possible that they can first produce nitrous acid from nitrate followed by the generation of ammonium. Only U. thermosphaericus had significantly large growing ability in the medium contained 1000 ppm of "Lannate®-45 water lenitive" (carbamate insecticide) and 400 ppm of "Ortran®" (organophosphorus insecticide) compared with the same concentration-level in the contrast medium without adding the pesticide.

Rebaudioside A potently stimulates insulin secretion from isolated mouse islets: Studies on the dose-, glucose-, and calcium-dependency.
ABUDULA, R, JEPPESEN, PB, ROLFSEN, SE, XIAO, J, HERMANSEN, K,
Metabolism, 53 (10) (2004) 1378-1381
Extracts of leaves of the plant Stevia rebaudiana Bertoni (SrB), have been used for many years in traditional treatment of diabetes in South America. Stevia leaves contain diterpene glycosides, stevioside and rebaudioside A being the most abundant. Recently, it was demonstrated that stevioside stimulates the insulin secretion both in vitro and in vivo. Subsequently, we wanted to elucidate the influence of rebaudioside A on the insulin release from mouse islets using static incubations, as well as perifusion experiments. Rebaudioside A (10(-16) to 10(-6) mol/L) dose-dependently stimulated the insulin secretion in the presence of 16.7 mmol/L glucose (P <.05). The stimulation of insulin release occurs at a concentration of 10(-14) mol/L rebaudioside A, and maximal insulin response was obtained at 10(-10) mol/L (P <.01). Rebaudioside A stimulates insulin secretion in a glucose-dependent manner (3.3 to 16.7 mmol/L) and only potentiated insulin secretion at glucose > 6.6 mmol/L. The effect of rebaudioside A is critically dependent on the presence of extracellular Ca(2+), ie, rebaudioside A-induced insulin stimulation at high glucose disappears in the absence of extracellular Ca(2+). In conclusion, rebaudioside A possesses insulinotropic effects and may serve a potential role as treatment in type 2 diabetes mellitus.

Anti-platelet effects of different phenolic compounds from Yucca schidigera Roezl. Bark.
OLAS, B, WACHOWICZ B, STOCHMAL, A, OLESZEK, W,
Platelets, 13 (3) (2002) 167-173
Resveratrol (3,4,5-trihydroxystilbene) has been reported to have a variety of anti-inflammatory, anti-carcinogenic, anti-fungal and anti-platelet effects. It occurs naturally in different medicinal plants. Recently, resveratrol and other related phenolic compounds including trans-3,3,5,5-tetrahydroxy-4-methoxystilbene and yuccaols A and C were isolated from the bark of Yucca schidigera. The aim of the present study was to evaluate in vitro the effects of these compounds on platelet aggregation induced by thrombin and ADP. Pretreatment of platelets with resveratrol or other tested phenolics (1-25 g/ml) slightly reduced platelet aggregation stimulated by 5 M ADP (P < 0.05) or 10 M ADP (P < 0.005). The comparison of the inhibitory effects of tested compound in thrombin-induced platelet aggregation revealed that phenolic showed even stronger antiplatelet actions than resveratrol. These compounds also had an inhibitory effect on the thrombin-induced enzymatic platelet lipid peroxidation determined as the level of thiobarbituric acid reactive substances.

Antioxidant Properties of Yucca schidigera Products.
OLESZEK, W, SITEK, M, STOCHMAL, A, CHEEKE, P,
in Biologically-Active Phytochemicals in Food. (RSC, Special Publication, No. 269). PFANNHAUSER, W, et al. (Edit.) Royal Society of Chemistry, 2001 303-306
Yucca schidigera (Agavaceae) grows in the deserts of Baja California. Its extract (condensed juice mechanically pressed from the trunk) or powder (pulverized dry trunks) are commonly used as additive in the cosmetic and soft drink industries. They are regarded as a "generally recognized as safe" (GRAS) products, approved by the Food and Drug Administration as a food additive. They are also fed to livestock and poultry to improve health and productivity. It is believed that the main components of yucca products, responsible for beneficial effect on animal performance are steroidal saponins. They make up about 10% of yucca trunk dry matter. Relatively little has been known on the appearance of phenolics in yucca products. The only report on this group of compounds in yucca indicated the presence of resveratrol (trans-3,4',5-trihydroxystilbene). Resveratrol was first identified in the skin of grapes and was recognized as one of the strongest natural antioxidant responsible, at least in part, for the reduced risk of cardiovascular disease in man from moderate consumption of red wine. It shows also antimutagenic, cancer chemopreventive, apoptosis inducing, dioxin preventing, antialergic and phytoestrogen activities.

Resveratrol and other phenolics from the bark of Yucca schidigera Roezl.
OLESZEK W, SITEK M, STOCHMAL A, PIACENTE S, PIZZA C, CHEEKE P,
J. Agricultural and Food Chemistry, 2001 Feb;49(2):747-752
Five phenolic constituents have been identified in Yucca schidigera bark, and their structures were established by spectral (FABMS and NMR) experiments. These included two known stilbenes, trans-3,4',5-trihydroxystilbene (resveratrol) and trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene, as well as three novel compounds, yuccaols A, B, and C, with spiro-structures rarely occurring in the plant kingdom. It is suggested that yuccaols A-C are biosynthethized via attachment of a stilbenic derivative to the carbocationic intermediate of the oxidative flavanone-flavonol conversion.

Enhancer for producing calcitonin.
HIROYUKI MATSUMOTO, MASARU FUNADA, SHOJI MASUKO,
Nippon Yushi K.K. JAPAN 05310563 A 19931122
PURPOSE: To obtain an enhancer for producing calcitonin useful for treating osteoporosis, essential hypercalmia, primary hyperthyreosis, vitamin D toxicosis, bone metastases of cancer, etc.
CONSTITUTION: An enhancer for producing calcitonin comprises one or more of 22-38C straight-chain saturated alcohols such as octacosanol, tetracosanol or triacontanol as active ingredients. The enhancer is optionally mixed with various kinds of pharmaceutically permissible additives and pharmaceutically manufactured into a dosage form of water dispersion, solid substance or liposoluble liquid state. The dose is preferably about 0.01-100mg/kg body weight for an intake of octacosanol. The 22-38C straight-chain saturated alcohols are obtained as a mixture of straight-chain saturated alcohols by extrecting and purifying mainly from a wheat germ oil and a rice bran oil. Higher the purity of octacosanol in the mixture of straight saturated alcohols is higher are the effects on production of calcitonin.