Product name: Rhapontin
Synonym name: Ponticin; Rhaponticin
Catalogue No.: BP1207
Cas No.: 155-58-8
Formula: C₂₁H₂₄O₉
Mol Weight: 420.414
Botanical Source: Rheum hotaoense
Physical Description:
Type of Compound: Stibene glucosides

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.

Description:

Rhaponticin(Rhaponiticin) has a noticeable antidiabetic effect and could be potentially used as a new agent to treat type 2 diabetes mellitus and its complications, it can alleviate liver steatosis and improve blood glucose and lipid profiles in KK/Ay diabetic mice.

References:

Planta Med. 2009 Apr;75(5):472-7.    

Rhaponticin from rhubarb rhizomes alleviates liver steatosis and improves blood glucose and lipid profiles in KK/Ay diabetic mice.   

We isolated several stilbene compounds including rhaponticin (Rhaponiticin,3',5-dihydroxy-4'-methoxystilbene 3- O-beta- D-glucopyranoside) from extracts of rhubarb rhizomes. These compounds showed significant hypoglycemic effects in streptozotocin (STZ)-induced type 1 diabetic rats and mice. 

METHODS AND RESULTS:

In this study, we investigated the effect of rhaponticin on glucose utilization, lipid metabolism, and liver and heart function in a KK/Ay type 2 diabetic mouse model. The results showed that oral administration of rhaponticin (125 mg/kg) significantly reduced blood glucose levels and improved oral glucose tolerance of KK/Ay diabetic mice. Elevated plasma triglyceride (TG), low density lipoprotein (LDL), cholesterol (CHO), non-esterified free fatty acids (NEFA), and insulin levels were also markedly attenuated. Serum enzymatic activities of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the rhaponticin-treated group significantly decreased in comparison to the untreated model group. Livers of rhaponticin-treated mice had relatively normal cellular size and decreased fibrosis and steatosis. In addition, rhaponticin administration caused a remarkable increase in the hepatic glycogen content and a significant reduction in the hepatic triglyceride content. 

CONCLUSIONS:

These results indicate that rhaponticin has a noticeable antidiabetic effect and could be potentially used as a new agent to treat type 2 diabetes mellitus and its complications.    

HPLC of Rhapontin

HNMR of Rhapontin

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

Introduction/Overview

As an important treasure trove for drug discovery, natural products continue to provide modern medicine with lead compounds with novel structures and diverse activities. Rhapontin, also known as Rhapontin or Rhapontin, is a type of stilbene compound isolated from traditional medicinal plants such as Rheum spp. Its CAS number is 155-58-8, and its chemical structure is 3,3 ', 5-trihydroxy-4' - methoxystilbene-3- β - D-glucoside. For a long time, plants containing emodin have been used in traditional medicine for purposes such as defecation and anti-inflammatory. With the deepening of modern pharmacological research, the biological activity spectrum of rhein has been greatly broadened, and its multiple pharmacological effects as an oral effective SIRT1 agonist and AMPK activator have been gradually revealed, showing anti-inflammatory, anti fibrosis, antithrombotic, anti allergic and anti diabetes potential. Especially in difficult to treat disease models such as inflammatory bowel disease (such as ulcerative colitis) and pulmonary fibrosis, it has shown clear therapeutic effects, making it a highly studied subject in the field of natural product pharmacology. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, mechanisms of action, medicinal properties, and clinical application prospects of rhubarb glycoside, in order to provide comprehensive scientific references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The molecular formula of rhubarb glycoside is C21H24O9, with a molecular weight of 420.4140. Its core structure is a stilbene (stilbene) skeleton, with hydroxyl substitution at positions 3, 3 ', and 5, methoxy substitution at position 4', and a β - D-glucose group connected by an O-glycosidic bond at position 3. This structure belongs to the family of astragalosides and is the material basis for its biological activity.

In terms of physicochemical properties, the lipid water partition coefficient (LogP) of rhubarb glycoside is 0.6825, indicating that it has a certain degree of hydrophilicity. Its topological polar surface area (TPSA) is 149.0700 Å ², reflecting the strong polarity brought by multiple hydroxyl and sugar groups in the molecule. The water solubility data is 3.3989 (usually measured in mg/mL or log mol/L, relative here), indicating moderate solubility in water, which is beneficial for oral absorption. These preliminary parameters related to medicinal properties suggest that rhubarb glycoside has a good starting point for drug like properties. In addition, its blood-brain barrier permeability is predicted to be low, suggesting that the role of the central nervous system may be limited; The hERG inhibition test was negative, indicating a low potential risk of cardiac toxicity; The Ames test result is 0.0, which preliminarily supports its non mutagenicity and good safety characteristics.

Plant sources and extraction methods

Rhubarb glycoside mainly comes from various plants in the Rheum genus of the Polygonaceae family, such as Rheum palmatum, Rheum tanguticum, and medicinal Rheum officinale. In the rhizomes of these plants, emodin often coexists with other anthraquinone and astragalus components. In addition, it has also been detected in some non Rheum plants such as Polygonum cuspidatum.

The extraction method follows the conventional process of natural product chemistry. The solvent extraction method is usually used, using methanol, ethanol, or ethanol water solutions of different proportions as solvents, to perform reflux extraction or ultrasound assisted extraction on dried and crushed plant materials. Subsequently, preliminary enrichment and purification were carried out using macroporous adsorption resin (such as AB-8, D101) column chromatography, and eluted with water and different concentrations of ethanol. Rhubarb glycoside is usually obtained in the partially eluted portion with low to medium concentrations of ethanol. Further purification can be achieved through methods such as silica gel column chromatography, preparative high-performance liquid chromatography (HPLC), or recrystallization. The optimization of extraction process often focuses on factors such as solvent concentration, solid-liquid ratio, extraction temperature, and time to improve extraction rate and purity. Modern analysis and identification mainly rely on high-performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR) techniques.

Pharmacological activity research

A large number of preclinical studies have revealed the extensive and significant pharmacological activities of emodin, providing a basis for its multi-target therapeutic application.

1. anti-inflammatory activity Rhubarb glycoside has shown strong anti-inflammatory effects in various acute and chronic inflammation models. In a mouse ulcerative colitis model induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS), oral administration of rhubarb glycoside significantly reduced colon shortening, tissue edema, mucosal ulcers, and inflammatory cell infiltration. In lipopolysaccharide (LPS) - induced acute lung injury or asthma models, it can reduce the levels of inflammatory factors and the number of inflammatory cells in bronchoalveolar lavage fluid.
2. Anti fibrotic activity Rhubarb glycoside can effectively inhibit the process of tissue fibrosis. In the mouse pulmonary fibrosis model induced by bleomycin, treatment with rhubarb glycoside can alleviate pulmonary inflammation, reduce collagen deposition, and improve lung function. In both liver fibrosis and kidney fibrosis models, it can also inhibit the proliferation of activated hepatic stellate cells or renal fibroblasts, and reduce excessive deposition of extracellular matrix (such as collagen I, III, fibronectin).
3. Metabolic regulation and anti diabetes activity Rhubarb glycoside can improve insulin resistance and glucose and lipid metabolism disorders. In the model of type 2 diabetes mice induced by high-fat diet combined with streptozotocin, rhein can reduce fasting blood glucose, improve glucose tolerance, regulate blood lipid profile, and alleviate pancreatic β cell injury.
4. Cardiovascular protective activity Research shows that rhein has the effect of anti platelet aggregation and anti thrombosis, and can improve endothelial function, which has potential benefits for cardiovascular diseases such as atherosclerosis.
5. Laxative effect Related to the laxative effect of traditional rhubarb, emodin may affect the secretion and transport of intestinal fluids by regulating intestinal ion channels and aquaporins. However, its specific effects may be weaker or have different mechanisms compared to the well-known anthraquinone components in rhubarb, such as senoside. The relevant targets involve CFTR (cystic fibrosis transmembrane conductance regulator), SLC9A3 (sodium hydrogen exchanger 3), and aquaporins AQP3, AQP4, AQP8, etc.

Mechanism of action and molecular targets

The multiple pharmacological effects of rhubarb glycoside stem from its precise regulation of key signaling pathways and molecular targets within cells, with its core mechanism revolving around the activation of SIRT1 and regulation of the AMPK signaling pathway.

1. SIRT1/NLRP3 inflammasome axis SIRT1 is a NAD+- dependent histone deacetylase that plays a central role in energy metabolism, stress resistance, and inflammation inhibition. Rhubarb glycoside has been proven to be an orally effective SIRT1 agonist. Activated SIRT1 deacetylates key components of NLRP3 inflammasome, such as the NLRP3 protein itself, inhibiting its assembly and activation, thereby reducing caspase-1 cleavage and downstream maturation and release of interleukin-1 β (IL-1 β) and IL-18. This is the key molecular mechanism by which emodin inhibits NLRP3 inflammasome dependent inflammatory responses, such as in ulcerative colitis and acute lung injury.
2. AMPK/TGF - β/Smad pathway AMPK is the central regulator of cellular energy metabolism. Rhubarb glycoside can activate AMPK. Activated AMPK can phosphorylate and inhibit the activation of downstream signaling molecules Smad2/3 of TGF - β 1, while possibly upregulating the expression of inhibitory Smad7, thereby blocking the classical TGF - β/Smad signaling pathway. This pathway is the core driving force for the occurrence and development of tissue fibrosis, therefore, rhubarb glycoside effectively inhibits myofibroblast differentiation, migration, and extracellular matrix synthesis through AMPK mediated TGF - β/Smad inhibition, exerting anti fibrotic effects.
3. Epithelial barrier repair In intestinal and lung epithelial injury models, emodin can significantly upregulate the expression of tight junction proteins (such as ZO-1, Occludin, Claudin-1), repair epithelial barrier function damaged by inflammation, and this effect may be related to the improvement of cellular energy metabolism, inhibition of inflammation, and oxidative stress after activation of SIRT1 and AMPK.
4. Metabolic regulation mechanism Its anti diabetes effect is closely related to the activation of AMPK and SIRT1. AMPK activation promotes glucose uptake and fatty acid oxidation in skeletal muscle and liver, while inhibiting gluconeogenesis; SIRT1 activation enhances mitochondrial biosynthesis and function by regulating transcription co activators such as PGC-1 α, collectively improving systemic insulin sensitivity and energy homeostasis.
5. Convenience related targets Preliminary research suggests that rhubarb glycoside may affect intestinal secretion by regulating CFTR chloride channels, or regulate intestinal water balance by affecting aquaporins such as SLC9A3 and AQP3/4/8. However, its specific strength of action and mechanism network still need to be further elucidated.

Evaluation of drug properties and pharmacokinetics

Based on its physical and chemical parameters, rhubarb glycoside exhibits good potential for medicinal properties. Its oral efficacy has been confirmed in multiple animal models.

Pharmacokinetic studies have shown that rhubarb glycoside can be absorbed in the gastrointestinal tract after oral administration, but its prototype glycoside form may undergo extensive metabolism in the body. The main metabolic pathways include: ① hydrolysis Under the action of intestinal microbiota or tissue esterases, glycosidic bonds are broken to generate its aglycone, emodin. Glycosides typically have stronger cell membrane permeability and biological activity, and many observed pharmacological effects may be attributed to nucleosides or their further metabolites. ② Combination reaction Glycosides and prototype drugs may undergo glucuronic acid binding or sulfation in the liver, forming more water-soluble metabolites that are excreted through bile or urine.

Existing data indicate that the in vivo process of rhubarb glycoside conforms to the characteristics of most plant polyphenolic components: moderate absorption, extensive metabolism, rapid distribution and elimination. Its absolute bioavailability needs to be accurately determined. The low permeability of the blood-brain barrier limits its direct application in central nervous system diseases, but it may also reduce the risk of central side effects. The clear hERG inhibition negative and Ames test negative results provide early support for its safety assessment. However, comprehensive preclinical pharmacokinetic (such as tissue distribution, excretion pathways) and toxicological (long-term toxicity, reproductive toxicity) studies still need to be systematically conducted to support their clinical translation.

Clinical application prospects and prospects

As a natural small molecule with multiple targets and effects, rhubarb glycoside has shown broad application prospects in the prevention and treatment of various chronic diseases.

1. Inflammatory bowel disease (IBD)Given its excellent anti-inflammatory and barrier repair effects in animal models of ulcerative colitis, rhubarb glycoside is expected to be developed as a novel oral drug or adjuvant therapy for the treatment of IBD, especially ulcerative colitis. Its mechanism of inhibiting NLRP3 inflammasome through SIRT1 provides a new strategy for IBD treatment that is different from traditional immunosuppressants.
2. Organ fibrosis disease For diseases such as idiopathic pulmonary fibrosis (IPF), liver fibrosis, and kidney fibrosis that currently lack highly effective anti fibrotic drugs, the mechanism of action of emodin inhibiting the TGF - β pathway through AMPK has high specificity and great development value.
3. Type 2 diabetes and metabolic syndrome Its role in regulating glucose and lipid metabolism and improving insulin resistance may make it a potential candidate drug for diabetes and its complication management, especially for patients with mild inflammation or fatty liver.
4. Other potential areas There is also room for exploration in the management of allergic diseases (such as asthma), thrombotic diseases, and chronic constipation based on their laxative effects.

However, there are still challenges and future research directions for clinical application: ① Deep exploration of mechanisms Further clarification is needed on the direct interaction mode between emodin and its active metabolites with targets such as SIRT1 and AMPK, and to explore whether there are other unknown important targets. ② Formulation optimization To improve its bioavailability, it may be necessary to develop novel drug delivery systems, such as nano formulations, phospholipid complexes, or prodrug strategies. ③ Preclinical and clinical research A systematic GLP toxicology evaluation must be completed, and rigorous clinical trials must be designed to verify its safety, efficacy, and optimal dosing regimen in humans. ④ Potential for combination therapy: Explore the joint application of rhein and existing standard treatment drugs (such as 5-ASA for IBD, pirfenidone for pulmonary fibrosis, and metformin for diabetes), which may produce synergistic effects and reduce their respective dosage and side effects.

Conclusion

Rhubarb glycoside is a natural active compound with important research value discovered from traditional medicinal plants. Its chemical structure is clear, with both oral efficacy and good preliminary safety characteristics. The most prominent feature is that it synergistically activates SIRT1 and AMPK, two key proteins that play a "guardian" role in metabolism, inflammation, and fibrosis, forming a sophisticated multi-target action network, thereby exerting comprehensive therapeutic effects in anti-inflammatory, anti fibrosis, metabolic regulation, and other aspects. Although there are still a lot of pharmacokinetic, toxicological and clinical efficacy studies to be completed before transforming it into clinical drugs, the existing preclinical evidence has fully demonstrated the great potential of rhein in the treatment of inflammatory bowel disease, organ fibrosis, diabetes and other major chronic diseases. With the continuous deepening of modern research on natural products and the application of systems biology technology, rhubarb glycoside is expected to transform from a traditional medicinal active ingredient into a modern drug lead compound derived from nature and acting on key pathways, bringing new therapeutic hope to patients with related diseases.