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Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its Metabolite Steviol
S. rebaudiana bertoni possesses anti-inflammatory and antitumor promoting properties; however, not much information was available to explain its activity. Stevioside at 1mm significantly suppress lipopolysaccharide (LPS) - induced release of INF- alpha, Interleukin (IL)-1beta slightly suppressed nitric oxide release in THP-1 cells without exerting any direct toxic effect, whereas Steviol at 100μM did not. Activation of I kappa B kinases (IKK) beta and transcription factor NF-kappa B were suppressed by Stevioside as demonstrated by Western blotting.

This study suggested that Stevioside attenuates synthesis of inflammatory mediators in LPS- stimulated THP-1cells by interfering with the IKK beta and NF- kappa B signaling pathway and Stevioside–induced TNF-alpha secretion is partially mediated through TLR4 20.

Effect of Stevioside on Cardiovascular System
IsoSteviol is a derivative of Stevioside, a constituent of S. rebaudiana, which is commonly used as a non- caloric sugarsubstitute in Japan and Brazil.The study was conducted on rat: cultured rat aortic smoothmuscle cells which were pre incubated with isoSteviol, thenstimulated with angiotensin II, followed by [(3) H] thymidineincorporation and endothelin-1 Secretion was examined.IsoSteviol (1-100micromol/l) inhibits angiotensin-II-inducedDNA synthesis and endothelin-1secertion.Measurement of 2’7’-dichlorofluorescin diacetate, a redoxsensitive fluorescent dye, showed an isoSteviol-mediatedinhibition of intracellular reactive oxygen species generated bythe effects of angiotensin II. The inductive properties of angiotensin II on extra cellularsignal-regulated kinase (ERK) phosphorylation were foundreversed with isoSteviol and antioxidants such as Nacetylcysteine.In conclusion this study speculates that isoSteviol inhibitsangiotensin-II-induced cell proliferation and endothelin-1secretion via attenuation of reactive oxygen species generation.Thus, this study provides important insights that maycontribute to the effects of isoSteviol on the cardiovascular system21.

Effect on carbohydrate metabolism
In isolated perfused rat liver stevioside inhibit transport of monosaccharide i.e. glucose fructose and galactose in both the direction. It halves transport rate of glucose into liver and also inhibits hepatic release of glucose. In hamsters fed stevioside for 12 weeks, glucose absorption was found to inhibit by leading to decreases in the body weight of hamster. Oral administration of stevioside (7% of diet) in rats for 56 days caused no change in blood sugar level. However an increase in plasma glucose level was found when stevioside was given intravenous infusion. The magnitude of effect of intake of stevioside on blood glucose level in vivo is still under investigation and there are reports indicating decrease in the blood glucose level and hepatic glucose level in rats after four weeks and in human volunteers eight hours after consumption of extract.

Hemodynamic Effects
According to a 4-week study by Maki et al. (2008), 1,000 mg/day rebaudioside Adid not significantly alter resting, seated systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, or 24-hour ambulatory blood pressure responses in patients with low-normal to normal blood pressure compared with a placebo. 1,000 mg/day is 7-10 times the predicted average daily intake and 2-4 times the daily intake for high intake consumers. A secondary analysis noted small changes in diastolic blood pressure and mean arterial pressure. The investigators assert that those findings are clinically insignificant 22.

Conclusion with future prospects
The leaves of this splendid plant are 30 times sweeter than sugar; with zero calories where as pure extract is 300 times sweeter than sugar. This sweet-honey -leaf herb is likely to become the major source of high potency sweetener for the growing natural food market, in the years to come. Stevia finds its use as a natural sweetener, replacing the chemical sweeteners and even table sugar; the sweetness in leaf is due to the presence of an intensive-sweetening agent called stevioside and the leaf by itself is about 20 to 30 times sweeter than sugar. The leaf has stevioside of 10-12% on dry weight basis. Stevia is a new promising renewable raw material for the food market. The market potential for this natural sweetener is steel untapped. It is estimated that about 30 million Indians are presently suffering from diabetes and it is estimated that by 2025 India’s contribution to the diabetic global population would be a whopping 89 million. With such a huge share of the population being diabetic, the new ventures in the food industry are focused entirely on them.

There is growing international market for Stevia as well as. There are offers to buy container loads of Stevia leaves at a price of 25 dollars per kilo. As mentioned earlier international demand are only for high quality Stevia leaves having minimum 9% Stevioside content. There is no buyer for Stevia leaves having less than 8% Stevioside content. Stevia cultivation can be successful venture provided you are able to produce high quality leaves having minimum Stevioside content of 9% at the same time produce optimum quality of marketable leaves per acre to keep the production cost below Rs. 25 per kilo on five years basis.

The demand for high potency sweeteners is expected to increase Worldwide. The increasing in the number of diabetic patients and health conscious individuals would push forward the need for alternatives to sugar. Stevia is a potential alternative source for replacing artificial sweeteners like saccharin, aspartame, asulfam, etc. Unlike many low calorie sweeteners, stevioside is stable at High temperature and over a pH range of 3 -9. Steps need to be properly aligned to exploit the natural sweetness of Stevia.

It’s time to streamline necessary forces to have access to Stevia. Initiative needs to be undertaken to promote this natural sweetener and create product awareness. This would be the right approach to unlock the sweetness of this herb in our day to-day life.

Authors are thankful to Head, department of Pharmaceutical Science, V.N.S. Institute of Pharmacy, Bhopal (M.P.) for providing necessary facilities.

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