Product name: Rebaudioside A
Synonym name: Stevioside A3; Rebiana
Catalogue No.: BP1198
Cas No.: 58543-16-1
Formula: C₄₄H₇₀O₂₃
Mol Weight: 967.021
Botanical Source: Stevia rebaudiana (Bertoni) Hemsl.
Physical Description:
Type of Compound: Diterpenoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.




Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.

HPLC of Rebaudioside A

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Globally, the incidence rate of metabolic diseases such as diabetes, obesity and dyslipidemia continues to rise, which has become a serious public health challenge. Developing safe and effective treatment and intervention strategies, especially searching for active lead compounds from natural products, is one of the important directions in current drug development. Stevia rebaudiana（Stevia rebaudiana Bertoni, as a traditional sweet plant, has been widely used as a food additive due to its high sweetness and low calorie content, which is rich in steviol glycosides in its leaves. Rebaudioside A (Reb A) is one of the steviol glycosides with the highest sweetness and closest taste to sucrose in stevia. In recent years, research has gradually revealed that rebaudin A is not only an excellent natural sweetener, but also a potential drug lead molecule with multiple biological activities. Its pharmacological effects have surpassed simple taste regulation, demonstrating significant potential for lowering blood sugar, regulating blood lipids, and anti obesity. Its mechanism of action involves precise regulation of multiple key physiological processes such as insulin secretion, glucose metabolism, cholesterol synthesis and clearance. This article aims to provide a systematic review of the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, pharmacological characteristics, and clinical application prospects of rabidicin A, in order to provide comprehensive scientific references for the deep development and utilization of this natural product.

Chemical structure and physicochemical properties

The chemical name of Rabobasidin A is 13- [(2-O - β - D-glucopyranosyl - α - D-glucopyranosyl) oxy] kaempferol-16-en-18-acid - β - D-glucopyranosyl ester, CAS number 58543-16-1. Its molecular formula is C44H70O23 and its molecular weight is 967.0210 daltons.

Structurally, rebaudin A belongs to the tetracyclic diterpenoid class, with steviol as the aglycone. Its structural feature is that the carboxyl group at position C19 of steviol alcohol forms an ester bond with a β - D-glucosyl group, and a sugar chain composed of three sugars is connected to the hydroxyl group at position C13. The sugar chain sequence is β - D-glucosyl - (2 → 1) - α - D-glucosyl - (3 → 1) - β - D-glucosyl. This unique glycosylation pattern is the structural basis for its high sweetness (about 200-400 times that of sucrose) and good taste (with weaker aftertaste).

In terms of physical and chemical properties, rebaudin A is a white to off white crystalline powder. The calculated lipid water partition coefficient (LogP) is -0.6794, indicating that it has good hydrophilicity. The topologically polar surface area (TPSA) is as high as 374.1300 Å ², which is consistent with the presence of multiple hydroxyl and sugar ring structures in its molecule, and also indicates its strong hydrogen bonding ability. Its water solubility value is 2.2394 (usually measured in mg/mL or log mol/L, indicating a certain solubility in water, but not extremely high). These properties collectively determine the distribution and metabolic characteristics of rebaudin A in organisms.

Plant sources and extraction methods

Ruibaodi glycoside A is mainly derived from the Asteraceae plant Stevia rebaudiana（Stevia rebaudiana Bertoni's dried leaves. Stevia is native to the border region between Paraguay and Brazil in South America, and is now widely cultivated in Asia, North America, and other regions. The total content of steviol glycosides in leaves accounts for about 10% -20% of dry weight, among which the content of rebaudin A varies greatly depending on the variety, cultivation conditions, harvest season, and processing technology, usually between 2% -8%. Through modern breeding techniques such as hybridization and mutagenesis, stevia varieties with significantly increased levels of rebaudin A have been cultivated.

The extraction and purification of rebaudin A from Stevia leaves is a multi-step process that mainly includes:
1. Preprocessing and Extraction Dry stevia leaves are usually extracted using hot water or alcohol water solutions (such as ethanol and methanol) after being crushed, and the hydrophilicity of glycosides is utilized to dissolve them from plant cells.
2. Preliminary purification After filtration and concentration, the extraction solution is used to remove impurities such as proteins, pigments, and tannins through methods such as flocculation and adsorption (such as using activated carbon or macroporous adsorption resin).
3. Separation and refinement The preliminary purified glycoside mixture needs to be further separated to obtain high-purity rebaudin A. Key technologies include:
* Chromatographic separation method Preparation based high-performance liquid chromatography (HPLC) or simulated moving bed chromatography (SMB) are currently the most effective methods for obtaining high-purity (>95%) rebaudin A, but the cost is relatively high.
* Crystallization method The use of the difference in solubility of rebaudin A in different solvents (such as water alcohol systems) for recrystallization by controlling temperature, concentration, and other conditions is a commonly used purification method in industry.
* Enzymatic modification Using specific glycosidases to glycosylation or deglycosylation modify other steviol glycosides (such as steviol glycosides) in the extract can selectively increase the yield of rebaudin A.
4. Drying and finished products: The refined solution is concentrated, spray dried or vacuum dried to obtain the final product.

Optimizing the extraction and purification process, improving the yield and purity of Rabobasidin A, while reducing costs, is one of the key steps in achieving its large-scale pharmaceutical development.

Pharmacological activity research

A large number of in vitro and in vivo studies have shown that rebaudin A has a wide range of pharmacological activities, mainly concentrated in the field of metabolic regulation.

1. Hypoglycemic activity Ruibaodi glycoside A has inhibitory activity against alpha glucosidase, with an IC50 value of 35.01 μ g/mL. This enzyme is located at the brush border of the small intestine and is responsible for catalyzing the breakdown of dietary polysaccharides into absorbable monosaccharides. Inhibiting this enzyme can delay the digestion of carbohydrates and absorption of glucose, thereby reducing postprandial blood glucose peak. In diabetes animal models (such as streptozotocin induced diabetes rats), oral rebaudioside A can significantly reduce fasting and postprandial blood glucose levels and improve glucose tolerance in a dose-dependent manner.

2. Stimulate insulin secretion Research has confirmed that rebaudin A can stimulate pancreatic beta cells to secrete insulin in a glucose dependent manner. In the presence of glucose, it increases the ATP/ADP ratio in beta cells, closes ATP sensitive potassium ion (KATP) channels, causes cell membrane depolarization, voltage dependent calcium channel opening, calcium ion influx, and ultimately triggers insulin vesicle exocytosis. This "glucose dependent" characteristic reduces the risk of hypoglycemia when blood sugar is normal and provides an advantage in safety.

3. Regulating blood lipid metabolism Ruibaodi glycoside A exhibits clear lipid-lowering effects. The mechanism involves inhibiting the activity of the rate limiting enzyme for cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). At the same time, it can activate the sterol regulatory element binding protein (SREBP) signaling pathway, especially SREBP-2, thereby upregulating the expression of low-density lipoprotein receptor (LDLR) on the cell surface. The increased expression of LDLR promotes the uptake and clearance of low-density lipoprotein cholesterol (LDL-C) in the blood by tissues such as the liver, thereby reducing plasma total cholesterol and LDL-C levels. In animal models of obesity or hyperlipidemia induced by a high-fat diet, rebaudin A can effectively reduce weight gain, lower serum triglycerides, total cholesterol, and LDL-C, and increase high-density lipoprotein cholesterol (HDL-C).

4. Anti obesity potential In addition to indirectly affecting body weight by regulating blood lipids, some studies suggest that rabidic acid A may exert anti obesity effects by affecting appetite regulating hormones (such as GLP-1, PYY), increasing energy expenditure, or affecting adipocyte differentiation. As a zero calorie sweetener that replaces dietary sugar, it itself helps reduce energy intake.

5. Other activities There are also reports suggesting that Rabeprizin A may have auxiliary benefits such as anti-inflammatory, antioxidant, and antihypertensive effects (possibly related to improving endothelial function), which complement its overall effect of improving metabolic disorders.

Mechanism of action and molecular targets

The multiple pharmacological activities of ribavirin A stem from its interaction with multiple molecular targets and signaling pathways, forming a networked mechanism of action.

1. Core hypoglycemic mechanisms and targets：

   • Direct promotion of insulin secretion pathway The core lies in the regulation of KATP channels in pancreatic beta cells, which is a classic insulin secretion stimulation pathway.
   • Improve insulin sensitivity Research suggests that rebaudin A may act on Insulin receptor (INSR)Enhance Insulin receptor substrate 1 (IRS1) Tyrosine phosphorylation and promotion Glucose transporter 4 (SLC2A4/GLUT4) Transposition to the cell membrane improves insulin sensitivity in peripheral tissues such as fat and muscle.
   • Regulating related nuclear receptors and enzymes Possible activation Peroxisome proliferator activated receptor gamma (PPARG)The nuclear receptor is a target of insulin sensitizer thiazolidinedione drugs, involved in regulating adipocyte differentiation and glucose and lipid metabolism. Correct Glucokinase (GCK) The potential regulation may affect the liver's glucose perception and metabolism. inhibit Dipeptidyl peptidase-4 (DPP4) The activity can prolong the activity of endogenous glucagon like peptide-1 (GLP-1), indirectly promoting insulin secretion and inhibiting glucagon.

2. Core lipid-lowering mechanism and targets：

   • Inhibit cholesterol synthesis: Direct inhibition HMGCR Reduce de novo synthesis of cholesterol within cells.
   • Promote cholesterol clearance: By activating SREBP The SREBP-2 signaling pathway is upregulated LDLR Gene transcription and protein expression accelerate the clearance of LDL-C in the bloodstream.

3. Signal pathway integration：
   The multiple effects of rabidicin A may be integrated through a common superior signaling molecule. For example, certain pathways activated by it may affect key energy metabolism and cell survival signaling pathways such as AMPK (AMP activated protein kinase), PI3K/Akt (phosphatidylinositol 3-kinase/protein kinase B), thereby coordinating their effects in glucose metabolism, lipid metabolism, and even anti-inflammatory effects.

Evaluation of drug properties and pharmacokinetics

Based on the provided pharmacological parameters and existing research, the preliminary evaluation of the pharmacological properties of Ribadine A is as follows:

• absorb As a highly polar and high molecular weight glycoside, the oral bioavailability of ribavirin A is expected to be low. It is mainly absorbed in the upper part of the small intestine through passive diffusion or possible carrier mediated methods. After ingestion, the peak time for blood drug concentration (Tmax) is usually around 1-2 hours.
• distribution The high molecular weight (967 Da), high TPSA, and negative LogP indicate that rebaudin A is difficult to penetrate the lipid bilayer, and its distribution in the body is mainly limited to extracellular fluid, making it difficult to penetrate the blood-brain barrier (predicted as low permeability), and the risk of central nervous system side effects is low.
• Metabolism Ruibaodi glycoside A itself is relatively stable in gastric acid, but after entering the intestine, it can be gradually hydrolyzed by glycosidase secreted by the colonic microbiota, first removing the terminal glucose group, and finally producing the glycoside steviol alcohol. Steviol can be absorbed into the portal circulation and mainly forms steviol glucuronide in the liver by binding with glucuronic acid, which is its main metabolite detected in plasma and urine. The metabolic level of the prototype drug of rabidicin A is relatively high in the human body.
• excretion Ruibaodi glycoside A and its metabolites are mainly excreted through the kidneys in urine, with some excreted through feces. The renal clearance rate of steviol glucuronide is relatively high.
• Preliminary evaluation of safety：
  • HERG inhibition Predicted as' no ', indicating a lower risk of causing prolonged QT interval in the heart and leading to apical torsion type ventricular tachycardia.
  • Genotoxicity The Ames test result is 0.0 (usually indicating no mutagenicity under test conditions), preliminarily indicating no genetic toxicity risk.
  • General toxicity Long term, extensive animal toxicology studies and human consumption history (as a food additive) have shown that rebaudin A is safe at conventional doses. It is not metabolized by the human body to provide heat and does not affect blood sugar. The main safety concerns are the potential gastrointestinal discomfort (such as bloating) that may occur at high doses, as well as allergic reactions in certain populations.

Overall, rebaudin A has good safety and clear activity, but its low membrane permeability and oral bioavailability may be important challenges for its development as a systemic drug. Using it as a functional food ingredient or developing it into drugs targeting local intestinal effects (such as alpha glucosidase inhibitors) is a more realistic approach. Structural modifications (such as prodrugs) or novel drug delivery systems (such as nano formulations) may help improve their drug properties.

Clinical application prospects and prospects

The clinical application prospects of Ribadine A are broad, mainly reflected in the following aspects:

1. As a functional food additive and dietary supplement This is currently the most mature application field. As a natural sweetener with high sweetness and zero calories, it is directly used for the diet management of diabetes and obesity patients, replacing sucrose and other synthetic sweeteners, which helps to control energy and carbohydrate intake. Meanwhile, its potential metabolic benefits can serve as a selling point for "functional sweeteners".

2. Developing natural medicines for the prevention and adjuvant treatment of metabolic diseases：

   • Pre diabetes and type 2 diabetes It can be developed as a plant medicine or compound preparation with α - glucosidase inhibition and mild insulin secretion promoting effects, for early intervention and auxiliary hypoglycemic treatment, especially suitable for patients with poor postprandial blood glucose control.
   • dyslipidemia Based on its clear mechanism of regulating blood lipids, it can be explored to develop it as a health product or drug to assist in lowering cholesterol, in combination with statins or for statin intolerant patients.
   • Metabolic syndrome For patients with multiple abnormalities such as blood glucose, blood lipids, and weight simultaneously, the multi-target effect of rabidicin A demonstrates the potential for comprehensive management.

3. Drug development and structural optimization：

   • lead compound The chemical structure of ribavirin A can be used as a lead compound for structural modification and optimization, aiming to improve its bioavailability, targeting, or enhance a specific activity (such as stronger HMGCR inhibition or DPP4 inhibition), thereby developing novel small molecule drugs.
   • combination therapy Studying its synergistic effect with existing hypoglycemic drugs (such as metformin, DPP4 inhibitors, SGLT2 inhibitors) or lipid-lowering drugs may discover more effective combination therapy options.

4. Challenges faced and future research directions：

   • Deep analysis of the mechanism of action More research is needed at the cellular and molecular levels to accurately elucidate the direct interaction modes and strengths with targets such as INSR, PPARG, GCK, and clarify the overall network regulation of these targets.
   • Clinical Evidence Enhancement Currently, most research is focused on animal experiments and in vitro models, and there is an urgent need to design rigorous, large sample randomized controlled clinical trials to confirm their exact efficacy and long-term safety in humans.
   • Breakthrough in formulation technology How to overcome the problem of poor absorption through advanced pharmaceutical methods is the key to promoting its conversion into drugs.
   • Standards and regulations We need to establish more comprehensive quality standards, pharmacological and toxicological evaluation guidelines, and registration approval pathways for rebaudin A (as a pharmaceutical ingredient).

Conclusion

Ruibaodi glycoside A, a natural steviol glycoside derived from stevia, has evolved from an excellent natural sweetener to a highly promising multi active molecule in the field of metabolic disease prevention and treatment. It exhibits comprehensive benefits in lowering blood sugar, regulating blood lipids, and combating obesity through multiple mechanisms such as inhibiting alpha glucosidase, glucose dependent stimulation of insulin secretion, inhibition of HMGCR, and upregulation of LDLR expression. Although it has certain limitations in oral absorption and bioavailability, its excellent safety, clear target of action, and diverse pharmacological activities have laid a solid foundation for its development in functional foods, dietary supplements, and new plant or chemical lead compounds. With more in-depth disclosure of its molecular mechanism, continuous advancement of clinical research and innovation of preparation technology, Rabodioside A is expected to play a more important and unique role in the process of human coping with global health challenges such as diabetes, dyslipidemia and obesity. Future research should focus on translational medicine, bridging the gap between its promising preclinical profile and proven clinical utility， Ultimately achieving a magnificent transformation from a "sweet substance" to a "health guardian".