Rebaudioside D (Reb D) is a minor steviol glycoside isolated from the leaves of Stevia rebaudiana Bertoni . It is a rebaudioside A derivative in which the hydroxy group at position 2 of the β-D-glucosyl ester moiety has been converted to the corresponding β-D-glucoside . With a molecular formula of C₅₀H₈₀O₂₈ and molecular weight of approximately 1129 g/mol , it is a high-intensity natural non-caloric sweetener. Due to its clean sweet taste with reduced bitterness compared to rebaudioside A, it is considered a "next-generation" sweetener .
Not applicable - this compound is primarily used as a natural sweetener rather than as a drug with specific biological targets.

Rebaudioside D (Reb D) exhibits stability when exposed to simulated stomach and small intestine fluids, similar to rebaudioside A, and is susceptible to hydrolytic degradation by enteric bacteria collected from the cecum . Incubation with rat liver microsomes indicates that Reb D is not expected to be metabolized by liver enzymes . Reb D is metabolized by gut microbiota to steviol, a compound whose safety has been widely studied . In vitro studies also demonstrate that Reb D regulates bile acid transport and inhibits bile acid efflux .
In vitro studies on rebaudioside D are limited, as the compound is primarily used as a natural sweetener rather than as a pharmacological agent with specific biological targets. As a steviol glycoside, rebaudioside D is not metabolized by human digestive enzymes and passes through the gastrointestinal tract largely intact. It may be partially metabolized by gut microbiota to steviol, which can be absorbed and excreted. The compound's sweet taste is mediated through interaction with the sweet taste receptors T1R2/T1R3 on the tongue, which are G protein-coupled receptors that detect sweet compounds. However, rebaudioside D is not typically studied for pharmacological effects beyond its sweetening properties.

Rebaudioside D (Reb D) administered at 50 mg/kg/day by oral gavage to C57BL/6J male mice fed a high-fat/high-sucrose diet for 12 weeks reduced weight gain and visceral adipose tissue weight compared to vehicle-treated controls . Liver triglycerides and cholesterol were lower, and hepatic lipid peroxidation was decreased in Reb D-treated mice. Reb D treatment was associated with significant enrichment of Faecalibaculum rodentium in the gut microbiota and increased secondary bile acid metabolism. Reb D also decreased the circulating level of lipopolysaccharide-binding protein (LBP), a marker of metabolic endotoxemia. Reb D did not affect glucose homeostasis, alter total caloric intake, induce weight gain, exacerbate obesity, promote hepatic steatosis, impair brown adipose tissue function, nor change skeletal muscle metabolism-related proteins .
In vivo studies on rebaudioside D are primarily focused on its safety and metabolic fate as a food ingredient rather than on therapeutic efficacy. The compound has been extensively studied for its safety as a natural sweetener, with numerous toxicological and metabolic studies conducted to support its regulatory approval for use in food and beverage products. Rebaudioside D is not metabolized by human digestive enzymes and is largely excreted unchanged, though some metabolism to steviol by gut microbiota may occur. The compound is non-caloric and does not affect blood glucose levels, making it suitable for use in products for diabetic and weight-conscious consumers.

No detailed enzyme assay or receptor binding assay protocols for Rebaudioside D (Reb D) are provided in the available search results. However, in vitro metabolic stability studies were conducted using simulated gastrointestinal fluids, rat liver microsomes, and rat cecal contents to evaluate hydrolysis and degradation .
For analytical chemistry applications, rebaudioside D is analyzed by high-performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (LC-MS) to determine its purity and concentration in stevia extracts and food products. The compound is separated from other steviol glycosides (such as rebaudioside A, stevioside, and rebaudioside C) based on its retention time and mass spectrum. For sensory evaluation, taste panels are used to assess the sweetness intensity and quality of rebaudioside D compared to sucrose and other sweeteners. These evaluations help determine its suitability for use in food and beverage applications.

Cellular assays for rebaudioside D are not commonly performed, as the compound is primarily used as a sweetener rather than as a pharmacological agent. In studies investigating the biological effects of steviol glycosides, cell lines may be treated with rebaudioside D or its metabolites to assess effects on glucose metabolism, insulin secretion, or other metabolic parameters. However, these studies are not standard applications for the compound, which is primarily used as a food ingredient. Cytotoxicity against mammalian cells may be assessed as part of safety evaluations, though the compound is generally considered safe for consumption.

Rebaudioside D (Reb D) was evaluated in a 12-week diet-induced obesity mouse study. Eight-week-old male C57BL/6J mice were fed a high-fat/high-sucrose (HFHS) diet and orally treated with 50 mg/kg/day of Reb D (or vehicle control) by daily gavage for 12 weeks. Food intake was measured three times per week, and body weight was assessed twice per week. At weeks 10 and 12, insulin and oral glucose tolerance tests were performed. At week 12, animals were anesthetized with isoflurane and euthanized by cardiac puncture. Tissues were harvested, and blood was collected in heparin-coated tubes and centrifuged for plasma analysis. Liver lipid content, gene expression, bile acids (in feces, plasma, and liver), and gut microbiota (via whole-genome shotgun sequencing) were analyzed .
A 28-day repeated exposure dietary toxicity study was conducted in Sprague-Dawley rats. Reb D was administered at target exposure levels of 500, 1000, and 2000 mg/kg body weight/day in the diet. General condition, behavior, hematology, serum chemistry, urinalysis, and macroscopic/microscopic organ findings were evaluated .
In vivo studies on rebaudioside D are primarily conducted as part of safety and toxicological evaluations to support its regulatory approval as a food ingredient. These studies include acute and repeated-dose toxicity studies in rodents and other species, genotoxicity assays, and reproductive and developmental toxicity studies. The compound's metabolic fate is studied using radiolabeled rebaudioside D to determine its absorption, distribution, metabolism, and excretion (ADME) characteristics. These studies have established that rebaudioside D is safe for human consumption at levels typically used in food and beverage products.

Rebaudioside D (Reb D) is not absorbed intact. It shows similar stability when exposed to simulated stomach and small intestine fluids and is susceptible to hydrolytic degradation by enteric bacteria collected from the cecum . Incubation with rat liver microsomes indicates that Reb D is not expected to be metabolized by liver enzymes . Following oral ingestion, it is metabolized by gut microbiota to the common aglycone steviol, which is then absorbed, conjugated to steviol glucuronide in the liver, and excreted primarily in urine . Plasma concentrations of Reb D and its final hydrolysis product (free/conjugated steviol) are consistent between animals administered Reb D or Reb A in the diet .
Pharmacokinetic properties of rebaudioside D have been characterized in the context of its use as a food ingredient. As a large, polar glycoside with a molecular weight of 1129.15, rebaudioside D is not absorbed intact from the gastrointestinal tract. It passes through the digestive system largely unchanged and may be partially metabolized by gut microbiota to steviol, which can be absorbed and excreted in urine. The compound's lack of systemic absorption contributes to its non-caloric nature and safety profile. Key PK parameters are determined using LC-MS/MS analysis of plasma, urine, and fecal samples following oral administration.

Rebaudioside D (Reb D) is not absorbed intact. It shows similar stability when exposed to simulated stomach and small intestine fluids and is susceptible to hydrolytic degradation by enteric bacteria collected from the cecum . Incubation with rat liver microsomes indicates that Reb D is not expected to be metabolized by liver enzymes . Following oral ingestion, it is metabolized by gut microbiota to the common aglycone steviol, which is then absorbed, conjugated to steviol glucuronide in the liver, and excreted primarily in urine . Plasma concentrations of Reb D and its final hydrolysis product (free/conjugated steviol) are consistent between animals administered Reb D or Reb A in the diet .
Toxicological evaluation of rebaudioside D has been extensively conducted to support its regulatory approval as a food ingredient. Standard toxicology assessments include acute and repeated-dose toxicity studies in rodents and other species, genotoxicity assays (Ames test, micronucleus test), and reproductive and developmental toxicity studies. The compound has been found to be safe for human consumption at levels typically used in food and beverage products. Rebaudioside D is generally recognized as safe (GRAS) for use as a sweetener in the United States and has received regulatory approval in many other countries. Its favorable safety profile supports its use as a natural, non-caloric sweetener.

[1]. Metabolism and toxicity studies supporting the safety of rebaudioside D. Int J Toxicol. 2013 Jul;32(4):261-73.

Rebaudioside D (Reb D) is naturally present in stevia leaves in trace amounts (approximately 0.4-0.5% of leaf dry weight). Due to its low natural abundance, commercial production is achieved through biotechnological methods including microbial fermentation and enzymatic bioconversion from rebaudioside A using UDP-glycosyltransferases . Reb D has received GRAS (Generally Recognized as Safe) status from the US FDA and has been recognized as safe by EFSA . It is approved for use as a tabletop sweetener and as a general-purpose non-nutritive sweetener in foods, other than infant formula and meat and poultry products, at levels consistent with good manufacturing practices . Reb D is soluble in DMSO (98 mg/mL) and is typically stored lyophilized at -20°C .

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Rebaudioside D is a rebaudioside derivative of rebaudioside A, in which the 2-hydroxyl group of the β-D-glucose ester moiety is converted to the corresponding β-D-glucose. It is present in small amounts in the leaves of Stevia rebaudiana and acts as a sweetener. It is a rebaudioside and a sophoroside. Its function is related to rebaudioside A, rebaudioside E, and β-D-Glcp-(1->2)-[β-D-Glcp-(1->3)]-β-D-Glcp. Rebaudioside D in Stevia rebaudiana has been reported, with relevant data. See also: Stevia rebaudiana leaves (partial).

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Rebaudioside D (Reb D) is a sweet-tasting compound belonging to the steviol glycoside family, extracted from the foliage of Stevia rebaudiana (Bertoni) Bertoni (Compositae), and has been recognized as a promising sugar substitute. The metabolic fate of Reb D, along with that of rebaudioside A (Reb A), was investigated using multiple in vitro systems, including simulated digestive juices from the stomach and small intestine, rat liver microsomes, and rat cecal contents, as well as through plasma analysis from rats enrolled in a dietary toxicity study. Both Reb D and Reb A exhibited comparable stability in simulated gastric and intestinal fluids and were both degraded by cecal-derived gut bacteria via hydrolysis. Incubation with rat liver microsomes suggested that neither compound undergoes metabolism by hepatic enzymes. Plasma levels of Reb D, Reb A, and their common terminal breakdown product (free or conjugated steviol) were similar across animals receiving dietary Reb D or Reb A. A 28-day repeated-dose dietary toxicity study in Sprague-Dawley rats compared the safety of Reb D (at targeted doses of 500, 1000, and 2000 mg/kg body weight/day) with that of Reb A (at 2000 mg/kg body weight/day). No treatment-related alterations in general condition or behavior were observed, nor were there any toxicologically significant changes in hematology, serum chemistry, or urinalysis. Macroscopic and microscopic examinations revealed no treatment-related abnormalities in any organ assessed. Overall, the outcomes from the group given 2000 mg/kg/day Reb D were comparable to those from the group given 2000 mg/kg/day Reb A.
Rebaudioside D is a natural, non-caloric sweetener derived from the leaves of Stevia rebaudiana. It is a steviol glycoside that is about 200-220 times sweeter than sucrose and has a clean sweetness profile with good stability. The compound is used as a high-potency sweetener in food and beverage products, particularly in products for diabetic and weight-conscious consumers. Rebaudioside D is not a drug and is not intended for therapeutic use. Its mechanism of action involves interaction with sweet taste receptors (T1R2/T1R3) on the tongue, which activate signaling pathways that result in the perception of sweetness. The compound's lack of calories and minimal effect on blood glucose make it a valuable alternative to sugar in the food industry.

C50H80O28

1129.1534

1128.483

C, 53.19; H, 7.14; O, 39.67

63279-13-0

71773169

White to off-white solid powder

1.6±0.1 g/cm3

1.670

-3.38

17

28

16

78

2080

31

C[C@@]12CCC[C@@]([C@H]1CC[C@]34[C@H]2CC[C@](C3)(C(=C)C4)O[C@H]5[C@@H]([C@H]([C@@H]([C@H](O5)CO)O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O)O[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)CO)O)O)O)(C)C(=O)O[C@H]8[C@@H]([C@H]([C@@H]([C@H](O8)CO)O)O)O[C@H]9[C@@H]([C@H]([C@@H]([C@H](O9)CO)O)O)O

RPYRMTHVSUWHSV-CUZJHZIBSA-N

InChI=1S/C50H80O28/c1-18-11-49-9-5-24-47(2,7-4-8-48(24,3)46(68)77-44-39(34(64)29(59)22(15-54)72-44)75-42-36(66)32(62)27(57)20(13-52)70-42)25(49)6-10-50(18,17-49)78-45-40(76-43-37(67)33(63)28(58)21(14-53)71-43)38(30(60)23(16-55)73-45)74-41-35(65)31(61)26(56)19(12-51)69-41/h19-45,51-67H,1,4-17H2,2-3H3/t19-,20-,21-,22-,23-,24+,25+,26-,27-,28-,29-,30-,31+,32+,33+,34+,35-,36-,37-,38+,39-,40-,41+,42+,43+,44+,45+,47-,48-,49-,50+/m1/s1

[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl] (1R,4S,5R,9S,10R,13S)-13-[(2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3,4-bis[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy]oxan-2-yl]oxy-5,9-dimethyl-14-methylidenetetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylate

Rebaudioside D; (-)-Rebaudioside D; Rebaudioside D, (-)-; 1SU114WXBX;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~88.56 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (2.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (2.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)