Stevioside and related compounds therapeutic benefits beyond sweetness - 2009

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Pharmacology & Therapeutics 121 (2009) 41–54

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Pharmacology & Therapeutics
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p h a r m t h e r a

Associate editor: I. Kimura

Stevioside and related compounds: Therapeutic benefits beyond sweetness
Varanuj Chatsudthipong ⁎, Chatchai Muanprasat
Department of Physiology,Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

a r t i c l e
Keywords: Diabetes Hypertension Sweetener Stevioside Therapeutics Toxicity

i n f o

a b s t r a c t
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 severalcountries. 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, andimmunomodulatory 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 safetyof 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. © 2008 Elsevier Inc. All rights reserved.

Abbreviations: ADI, acceptable daily intake CFTR, cystic fibrosis transmembrane conductanceregulator GFR, glomerular filtration rate GK, Goto-Kakizaki KATP, ATP-sensitive potassium channels LPS, lipopolysaccharide mABP, mean arterial blood pressure OAT, organic anion transporter PAH, p-aminohippurate PEPCK, phosphoenol pyruvate carboxy kinase STZ, streptozotocin TPA, 12-O-tetradecanoylphorbol-13-acetate

Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 1.1. Natural source . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2. Chemical structure and sweetness property . . . . . . . . . . . . . . 1.3. Extraction and purification . . . . . . . . . . . . . . . . . . . . . . Pharmacokinetics of stevioside . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Biological effects and potential therapeutic applications of stevioside and related 3.1. Anti-hyperglycemic effect . . . . . . . . . . . . . . . . . . . . . . . 3.1.1. Effect on glucoseabsorption . . . . . . . . . . . . . . . . . 3.1.2. Effect on glucose synthesis . . . . . . . . . . . . . . . . . . 3.1.3. Effect on insulin secretion and sensitivity . . . . . . . . . . . 3.2. Anti-hypertensive effect . . . . . . . . . . . . . . . . . . . . . . . 3.3. Anti-inflammatory and anticancer effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 42 42 43...
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