Product name: Emodin anthrone
Synonym name: Emodin-9-anthrone;Frangula emodin anthrone
Catalogue No.: BP4493
Cas No.: 491-60-1
Formula: C₁₅H₁₂O₄
Mol Weight: 256.257
Botanical Source:
Type of Compound:

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.

For Reference Standard and R&D, Not for Human Use Directly.

HPLC of Emodin anthrone

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. Anthraquinone compounds, as one of the major categories, are widely present in various medicinal plants and have various biological activities such as diarrhea, anti-inflammatory, and anti-tumor. Emodin anthraquinone (also known as Frangula emodin, CAS number: 491-60-1) is a reduced form of the anthraquinone compound Emodin and belongs to the anthraquinone derivative. For a long time, plants containing emodin anthrone (such as rat chestnut bark) have been used as laxatives in traditional medicine. With the deepening of modern pharmacological research, the biological activity spectrum of emodin anthrone has far exceeded traditional laxative effects, demonstrating potential in anti-inflammatory, anti-tumor, antiviral, and metabolic regulation. Especially in the context of the global novel coronavirus pneumonia (COVID-19) epidemic, it has been identified as an active compound that can block the interaction between SARS CoV-2 spike protein and host cell receptor ACE2, causing widespread concern. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, pharmacological evaluation, and clinical application prospects of emodin anthrone, in order to provide comprehensive scientific references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The chemical name of emodin anthrone is 1,3,8-trihydroxy-6-methyl-9,10-dihydroanthracene-9-one, with a molecular formula of C15H12O4 and a molecular weight of 256.2570. The core of its structure is the anthrone skeleton, where a central quinone structure is reduced to a ketone group, connecting two benzene rings (A ring and C ring). There are two hydroxyl groups at positions 1 and 3 on the A ring, and one hydroxyl group at position 8 and one methyl group at position 6 on the C ring. This substitution mode of trihydroxymethyl is the key pharmacophore basis for its various biological activities.

In terms of physicochemical properties, the lipid water partition coefficient (LogP) of emodin anthrone is 3.2225, indicating that it has a certain lipophilicity, but not highly hydrophobic. Its topological polar surface area (TPSA) is 77.7600 Å ², reflecting the polarity brought by multiple hydroxyl groups in the molecule. The water solubility value is 0.1252 mg/mL, which belongs to the category of slightly soluble to poorly soluble, posing a challenge for its formulation development. This compound usually appears as yellow to orange yellow crystals or powder. In the air, anthrone has an unstable structure and is easily oxidized to its corresponding anthraquinone form - emodin. This characteristic needs to be considered in extraction, storage, and in vivo metabolism processes.

Plant sources and extraction methods

Emodin anthraquinone is not widely present in its free form. It mainly serves as a precursor or metabolic intermediate for anthraquinone glycosides and is found in various Polygonaceae, Rhamnaceae, and Fabaceae plants. Common rich plants include:
1. Rheum officinale and Rheum palmatum for medicinal purposes Its rhizome is the main source of the traditional laxative "rhubarb", containing bound emodin anthrone glycosides (such as sennosides), which are hydrolyzed into active aglycones under the action of gut microbiota.
2. Frangula alnus Its bark (rat chestnut bark) is a traditional European laxative and also contains a large amount of anthraquinone glycosides. Its name "Frangula emodin" comes from this.
3. Cassia obtusifolia or Cassia tora Seeds also contain such components.

The extraction method usually follows the conventional process of natural product chemistry. Firstly, the plant materials are dried and crushed, and then subjected to heating reflux or ultrasound assisted extraction using organic solvents such as methanol, ethanol, or alcohol water mixtures in different proportions. After the crude extract is concentrated under reduced pressure, the acidic or amphoteric properties of anthraquinone components are utilized for preliminary separation using pH gradient extraction method: usually, free anthraquinone/anthraquinone is extracted with organic solvents (such as ether, chloroform) first, and then alkaline aqueous solutions (such as sodium bicarbonate, sodium carbonate, sodium hydroxide solution) are used for graded extraction of different acidic components. Rhubarb anthrone has weak acidity due to its phenolic hydroxyl group, and can dissolve as a salt in low concentration alkaline solutions. Further purification depends on column chromatography technology, such as silica gel column chromatography, Sephadex LH-20 column chromatography, etc., eluting with solvent systems with increasing polarity (such as petroleum ether ethyl acetate, chloroform methanol). High performance liquid chromatography (HPLC) and preparative thin layer chromatography (PTLC) are the key final steps for obtaining high-purity monomeric compounds. During the entire extraction and purification process, attention should be paid to avoiding light, low temperature, and inert gas protection to prevent the oxidation of anthrone.

Pharmacological activity research

Numerous in vitro and in vivo studies have revealed the extensive and complex pharmacological activities of emodin anthrone.

1. Diarrhea effect This is its most classic and extensively studied activity. Emodin anthraquinone and its glycosides exert a laxative effect by stimulating colonic peristalsis, inhibiting net absorption of intestinal water and electrolytes, and promoting intestinal secretion. Its effect is mild, but long-term use may lead to electrolyte imbalance and colon melanosis.

2. Anti inflammatory and immune regulatory effects Rhubarb anthraquinone has shown significant anti-inflammatory effects in various inflammatory models. It can inhibit the excessive production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6) and other pro-inflammatory factors in macrophages induced by lipopolysaccharide (LPS). Its anti-inflammatory mechanism is closely related to the inhibition of key inflammatory signaling pathways such as nuclear factor kappa B (NF - κ B) and mitogen activated protein kinase (MAPK).

3. Antitumor activity Research shows that rhubarb anthrone can inhibit the proliferation and induce apoptosis of many cancer cell lines (such as liver cancer, breast cancer, lung cancer, colon cancer, leukemia, etc.). Its anti-cancer mechanisms are diverse, including inducing cell cycle arrest (such as G2/M phase), activating caspase cascade reactions, regulating Bcl-2 family protein balance, inducing mitochondrial dysfunction, producing reactive oxygen species (ROS), and inhibiting tumor cell invasion and metastasis.

4. Antiviral activity One of the most notable discoveries in recent years is its potential to resist SARS-CoV-2 virus. Research has confirmed that emodin anthraquinone can effectively block the binding of viral spike protein (S protein) to angiotensin converting enzyme 2 (ACE2) receptors on the surface of human cells, thereby exerting inhibitory effects in the initial stage of viral invasion. In addition, it also exhibits certain inhibitory activity against other viruses such as Coxsackievirus and influenza virus.

5. Metabolic regulation effect In metabolic disease research, emodin anthrone has been identified as an effective selective inhibitor of 11 β - hydroxysteroid dehydrogenase type 1 (11 β - HSD1). 11 β - HSD1 converts inactive cortisone into active cortisol in liver and adipose tissue, locally amplifying glucocorticoid effects and associated with insulin resistance, obesity, and metabolic syndrome. The half maximal inhibitory concentrations (IC50) of emodin anthraquinone on human and mouse 11 β - HSD1 were 186 nM and 86 nM, respectively, demonstrating good inhibitory efficacy. In a diet induced obese mouse model, it can improve glucose tolerance, reduce fasting blood glucose, alleviate fatty liver and insulin resistance.

6. Kinase inhibitory activity Rhubarb anthrone has also been reported as an inhibitor of casein kinase 2 (CK2). CK2 is a widely expressed and multifunctional serine/threonine protein kinase that plays a central role in cell survival, proliferation, and stress response. Its overactivity is associated with various cancers and inflammatory diseases. Inhibition of CK2 may contribute to its anti-inflammatory and anticancer effects.

Mechanism of action and molecular targets

The multiple pharmacological activities of emodin anthrone stem from its interactions with multiple molecular targets, forming a complex network.

• Targets related to diarrhea Its laxative effect involves complex regulation of intestinal ion channels and transporters.

  • CFTR (cystic fibrosis transmembrane conductance regulator)Possible activation or regulation of CFTR chloride ion channels may increase chloride ion secretion in intestinal epithelial cells, thereby driving the secretion of sodium ions and water into the intestinal lumen.
  • SLC5A1 (Na+/glucose cotransporter 1) and SLC12A2 (Na+- K+-2Cl - cotransporter 1)May inhibit the absorption and transport of these sodium ions and accompanying solutes, reducing the intestinal reabsorption of water and electrolytes.
  • AQP3 (aquaporin 3)May affect the expression or function of colonic aquaporins, altering the transmembrane transport of water.
  • KCNJ13 (member 13 of the inward rectifying potassium channel subfamily J) and KCNMA1 (member 1 of the high conductivity calcium activated potassium channel subfamily M α)It may affect the membrane potential and ion secretion of epithelial cells by regulating the activity of potassium ion channels.
  • SCNN1B (epithelial sodium channel beta subunit)May inhibit epithelial sodium channels (ENaC) and reduce the absorption of sodium ions.

• Key enzymes and signaling pathway targets：

  • 11β-HSD1 As a selective inhibitor, emodin anthraquinone directly binds to and inhibits the enzyme activity, reducing the cortisol levels in local tissues (especially liver and fat), thereby improving glucose and lipid metabolism disorders. This is the core molecular mechanism for improving metabolic syndrome.
  • CK2 By inhibiting the kinase activity of CK2 and interfering with downstream signaling pathways involved in cell survival (such as Akt, NF - κ B), proliferation, and DNA damage repair, cancer cell apoptosis is induced and inflammatory response is suppressed.
  • NF - κ B pathway By inhibiting the activity of I κ B kinase (IKK) or the degradation of I κ B α, NF - κ B nuclear translocation is prevented, and the gene expression of a series of pro-inflammatory cytokines and chemokines is downregulated.
  • MAPK pathway It can inhibit the phosphorylation activation of ERK, JNK, and p38 MAPK, thereby affecting cell proliferation, differentiation, and stress response.
  • SARS-CoV-2 S protein-ACE2 interaction Through molecular docking and biophysical experiments, it has been confirmed that it can directly bind to virus S protein or host ACE2 receptor, with high affinity binding hindered by steric hindrance or conformational interference, thus blocking virus invasion.

• Other potential targets This also includes proteins related to cell cycle regulation (such as Cyclin B1/CDK1), apoptosis execution (Caspases, Bcl-2 family), and oxidative stress (Nrf2/ARE pathway). Its multi-target characteristics are not only the basis for its comprehensive therapeutic effect, but also may bring complex effects and potential side effects.

Evaluation of drug properties and pharmacokinetics

Based on the provided parameters and existing research, a preliminary evaluation of the pharmacological properties of emodin anthrone is conducted

• Preliminary analysis of drug properties The molecular weight of 256 Da conforms to Lipinski's "five rules", with a LogP value of approximately 3.2 in the ideal range (1-5) and a moderate TPSA value of 77.8 Å ². These parameters suggest that it has good oral absorption potential. However, poor water solubility (0.1252 mg/mL) is its main drawback, which may affect its bioavailability and needs to be improved through formulation techniques such as salt formation, solid dispersion, nanocrystals, cyclodextrin inclusion, etc.

• Preliminary Safety Assessment：

  • HERG inhibition The data shows' no ', indicating a low likelihood of causing QT interval prolongation (risk of apical torsion ventricular tachycardia) in the heart, which is a positive cardiovascular safety signal.
  • Ames test A value of 1.2 (usually expressed as a mutation rate ratio MR, negative if less than 2) suggests that it does not have significant bacterial gene mutation toxicity, but further mammalian cell genotoxicity testing is needed to confirm.
  • Blood-brain barrier (BBB) permeability A prediction of 'low' indicates that it is not easily accessible to the central nervous system. This may be advantageous for indications (diarrhea, metabolic disorders, antiviral) that primarily target the peripheral system (such as the intestine, liver, fat, lungs), as it may reduce central side effects; But it is not conducive to the treatment of central nervous system diseases.

• Pharmacokinetic characteristics Existing literature indicates that the pharmacokinetic behavior of emodin anthraquinone and its related anthraquinone compounds is complex.

  • Absorption and distribution After oral administration, the bound glycosides are rarely absorbed in the small intestine and are mainly hydrolyzed into aglycones (such as emodin anthrone) by the intestinal microbiota after reaching the colon for absorption. The absorption rate of free aglycones is moderate, but the first pass effect is significant. It is widely distributed in the body, but due to low BBB permeability, its concentration in brain tissue is minimal.
  • Metabolism The liver is the main metabolic site, undergoing phase II metabolism through a combination of glucuronidation and sulfation reactions to generate more water-soluble complexes. Oxidation reduction conversion may occur between anthrone and anthraquinone forms.
  • excretion Metabolites are mainly excreted from urine through the kidneys, and prototype drugs and some metabolites can also be excreted into the intestine through bile, resulting in enterohepatic circulation, which may prolong their action time but also increase intestinal irritation. Its own laxative effect also accelerates its excretion from the intestine.
  • challenge Oral bioavailability may not be high, with significant individual differences (influenced by gut microbiota) and potential drug drug interactions (affecting metabolic enzymes or transporters).

Clinical application prospects and prospects

The multi-target and multi activity properties of emodin anthrone provide possibilities for its application in multiple therapeutic fields, but also come with challenges.

1. Potential clinical application directions：

   • Metabolic diseases As a selective 11 β - HSD1 inhibitor, it is an attractive candidate drug for the treatment of type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and obesity related metabolic syndrome. Its effects on improving glucose and lipid metabolism and insulin resistance have been validated in animal models.
   • antiviral therapy Rhubarb anthrone can be developed as a lead compound for virus invasion inhibitors or as an adjuvant therapy for COVID-19 and other coronaviruses that rely on ACE2 or similar mechanisms for invasion.
   • Inflammatory diseases Based on its powerful anti-inflammatory and immune regulatory effects, it may be used to treat chronic inflammatory diseases such as colitis, arthritis, dermatitis, etc.
   • neoadjuvant therapy Its anti-cancer activity, especially the mechanism related to CK2 inhibition, may make it a sensitizer or combination drug component for chemotherapy or targeted therapy, for the treatment of certain malignant tumors.
   • Constipation treatment As the active form of traditional laxative ingredients, their related preparations (such as standardized plant extracts) can still be used for the treatment of short-term and intermittent constipation, but strict management is needed to avoid abuse.

2. Challenges and Prospects Faced：

   • Selective optimization Its multi-target nature is a double-edged sword. When developing drugs for specific diseases such as metabolic disorders, it is necessary to optimize the structure while maintaining efficient inhibition of the main target (such as 11 β - HSD1) and minimizing interference with unrelated targets (such as intestinal ion channels to avoid diarrhea side effects).
   • Optimization of drug properties The primary task is to address the issues of water solubility and oral bioavailability. Improvement can be achieved through structural modification (preparation of prodrugs, synthesis of derivatives) or advanced formulation strategies.
   • Deep evaluation of safety A comprehensive preclinical safety pharmacology and toxicology study is required, especially on the chronic toxicity, genetic toxicity, reproductive toxicity, and potential long-term effects on intestinal neuromuscular function (related to laxative abuse) of long-term administration.
   • Clarify the treatment window It is necessary to accurately define the window between the therapeutic dose and the laxative dose in clinical trials to ensure efficacy while minimizing gastrointestinal adverse reactions.
   • Conversion research Strengthen the research on the transformation from cell and animal models to human trials, and verify the authenticity of its mechanism of action and efficacy in the human body.

Future research should focus on: ① designing and synthesizing derivatives with greater selectivity and drug properties; ② Utilizing new technologies such as nano delivery systems to enhance targeting and bioavailability; ③ Conduct rigorous randomized controlled clinical trials, especially in the exploration of metabolic diseases and antiviral fields; ④ Conduct in-depth research on its interactions and synergistic effects when used in combination with other drugs.

Conclusion

Rhubarb anthrone, a natural anthrone compound derived from traditional laxatives, has demonstrated rich pharmacological activities and complex molecular mechanisms of action far beyond its traditional uses under the revelation of modern scientific research. From inhibiting 11 β - HSD1 to improving metabolism, blocking viral invasion, and regulating kinase and inflammatory pathways, its multi-target action characteristics reflect the unique advantages of natural products in intervening in complex disease networks. Despite facing challenges such as solubility, selectivity, and potential side effects in drug development, its clear activity, relatively clear targets, and preliminary good safety implications (such as low hERG inhibition risk) make it a highly valuable lead compound for development. Through rational drug chemical modification, pharmaceutical innovation, and systematic clinical development, emodin anthrone and its optimized derivatives are expected to provide new drug options for the treatment of metabolic diseases, viral infections, inflammation, and even tumors in the future, becoming another successful example connecting traditional medical wisdom with modern drug development.