Antioxidant, anti-diabetic and renal protective properties of Stevia rebaudiana

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Abstract

Background

Stevia rebaudiana Bertoni has been used for the treatment of diabetes in, for example, Brazil, although a positive effect on antidiabetic and its complications has not been unequivocally demonstrated. This herb also has numerous therapeutic properties which have been proven safe and effective over hundreds of years. Streptozotocin is a potential source of oxidative stress that induces genotoxicity.

Objective

We studied the effects of stevia leaves and its extracted polyphenols and fiber on streptozotocin induced diabetic rats. We hypothesize that supplementation of polyphenols extract from stevia to the diet causes a reduction in diabetes and its complications.

Design/Methods

Eighty Wistar rats were randomly divided into 8 groups; a standard control diet was supplemented with either stevia whole leaves powder (4.0%) or polyphenols or fiber extracted from stevia separately and fed for one month. Streptozotocin (60 mg/kg body weight, i.p) was injected to the diabetic groups on the 31st day. Several indices were analyzed to assess the modulation of the streptozotocin induced oxidative stress, toxicity and blood glucose levels by stevia.

Results

The results showed a reduction of blood glucose, ALT and AST, and increment of insulin level in the stevia whole leaves powder and extracted polyphenols fed rats compared to control diabetic group. Its feeding also reduced the MDA concentration in liver and improved its antioxidant status through antioxidant enzymes. Glucose tolerance and insulin sensitivity were improved by their feeding. Streptozotocin was also found to induce kidney damage as evidenced by decreased glomerular filtration rate; this change was however alleviated in the stevia leaves and extracted polyphenol fed groups.

Conclusion

The results suggested that stevia leaves do have a significant role in alleviating liver and kidney damage in the STZ-diabetic rats besides its hypoglycemic effect. It might be adequate to conclude that stevia leaves could protect rats against streptozotocin induced diabetes, reduce the risk of oxidative stress and ameliorate liver and kidney damage.

Introduction

Stevia rebaudiana Bertoni is a small perennial shrub that belongs to the family aster or chrysanthemum family. It grows primarily in the Amambay mountain range of Paraguay (Mizutani & Tanaka, 2002). However over 200 species of stevia have been found around the world. Stevia rebaudiana is the only species at present, which possesses the ability to sweeten. The leaves of the stevia shrub contain specific substances (glycosides), which produce a sweet taste but have no caloric value, apart from protein, fibers, carbohydrates, phosphorus, iron, calcium, potassium, sodium, magnesium, rutin (flavonoid), zinc, vitamin C and vitamin A (Kim, Choi, & Choi, 2002). Stevia extracts were used by South Americans for the treatment of diabetes for many years (Curi et al., 1986, Soejarto et al., 1982). Rebaudioside A and stevioside are the two main steviol glycosides found in the S. Rebaudiana herb and are the two predominant derivatives used in high potency sweeteners. Stevioside differs from rebaudioside A by having one less glucose moiety (Wheeler et al., 2008). However, little experimental work has been performed either to prove the clinical efficacy of these extracts in diabetes, to identify the potential active substance(s) in the extracts, or to reveal the mode of action. A number of animal studies have been conducted to investigate the effects of stevioside, having antihyperglycemic, insulinotropic, and glucagonostatic actions in diabetic rat (Jeppesen et al., 2002, Jeppesen et al., 2003, Jeppesen et al., 2000). This herb also has numerous therapeutic properties and has been proven in safety and effectiveness for hundreds of years. Stevia offers an ideal alternative to other sugars or sugar substitutes (Munro, Lirette, Anderson, & Ju, 2000). Chronic diabetic is set with complication such as diabetic nephropathy that causes widespread damage to small and large blood vessels, which is a marker for cardiovascular disease, a common cause of death in these patients. Unfortunately, besides having a number of side effects, none of the oral hypoglycemic agents have been successful in maintaining euglycemia and controlling long-term micro- and macro-vascular complications. During the last part of the 1980s, the FDA began seizing stevia from health food manufacturers without adequate explanation (Alvares, Bazzone, Godoy, Cury, & Botion, 1981). Approximately 200 manufacturers including all of the major food manufacturers showed interest in using stevia in the manufacturing of their products. Available toxicological information on stevia is inadequate to demonstrate its safety as a food additive or to affirm its status as GRAS. Stevia leaves used in the studies met all current specifications set by the Joint FAO/WHO Expert Committee on Food Additives (Carakostas, Curry, Boileau, & Brusick, 2008). It is considered by the most of investigators as not toxic, not mutagenic and not carcinogenic (Smirnova, 2001, Takahasshi et al., 2001). In the present study, the in-vivo antioxidant properties of stevia leaves were studied with respect to diabetic complications such as antioxidant, hyperlipidemia and nephropathy in streptozotocin (STZ) induced diabetic rats.

Section snippets

Proximate composition and antioxidant activity of stevia

The stevia leaf powder was obtained from the Institute of Himalayan Bioresource Technology, Palampur, India. The proximate analyses (moisture, ash, fibers, crude fats, proteins and carbohydrates) of all the samples were determined. The moisture and ash were determined using weight difference method. The nitrogen value, which is the precursor for protein of a substance, was determined by micro Kjeldahl method described by Pearson (1976), involving digestions, distillation and finally titration

Results and Discussion

Diabetes has been one of the major killer diseases of the present day life. This disease is not only genetic but is linked to lifestyle and stress, both physical and mental. Nearly 12% of population worldwide is suffering from diabetes. In this study, we examined oxidative stress markers in rats with STZ induced diabetes and its modulation on feeding of stevia. STZ is a generally employed compound for the induction of type-I diabetes in rats (Cameron and Cotter, 1999, Tomlinson et al., 1992).

Conclusion

All these results are quite interesting and very encouraging. One single plant could have multifaceted benefits. However, the study brings forth many questions which need further thorough investigation, like the mechanism of action of stevia leaves powder inactivating the STZ in the blood itself, or does it prevent its transport across into pancreatic and hepatic cells? Whether the extract simply mops off the reactive oxygen species or is it a chain breaking antioxidant? Whether the prevention

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      This is elucidated to take place via activation of Akt/Nrf2/HO-1 pathway and thus gives a well desired candidate as a dietary supplement for alternating the oxidative stress which can be age-dependent also [104]. In another animal model Wistar rats, stevia leaf and powdered extract (4.0%) demonstrated reduced lipid peroxidation and favourable modifications in anti-oxidation markers in diabetic rodents [1]. Even production of the wheat bread containing extracts of stevia preserves its anti-oxidant potential and thus it falls in the category of functional food [12].

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