Synonym name:
Catalogue No.: BP0533
Cas No.: 38840-23-2
Formula: C₂₁H₂₀O₁₀
Mol Weight: 432.381
Botanical Source: Dermocybe sanguinea, Polygonum cuspidatum , Rhus, Rheum spp. and Guanomyces polythrix

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

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

HPLC of Emodin 1-glucoside

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

Introduction/Overview

Emodin-1-O-glucoside (Emodin 1-glucoside, CAS No.: 38840-23-2) is an important natural anthraquinone derivative, attracting widespread attention in pharmacology and natural product chemistry due to its diverse bioactivity. As a typical representative of anthraquinone compounds, emodin-1-O-glucoside not only has a long history of application in traditional Chinese medicine, but its modern pharmacological research has also revealed its potential value in antiviral, anti-inflammatory, anti-tumor, and metabolic regulation. Especially in the context of the COVID-19 pandemic, emodin-1-O-glucoside is regarded as a promising anti-COVID-19 candidate compound because it can block the interaction between the SARS virus spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). In addition, the compound's inhibitory effect on casein kinase 2 (CK2) and its characteristics as a selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) provide a theoretical basis for its application in anti-inflammatory, anticancer, and metabolic disease treatment.

This paper aims to systematically review the chemical structure, plant origin, extraction method, pharmacological activity, and mechanism of action of emodin-1-O-glucoside, combined with its druggability evaluation and pharmacokinetic characteristics, to explore its potential and future development directions in clinical applications, and to provide references for further research and drug development of this natural product.

Chemical structure and physicochemical properties

Emodin-1-O-glucoside is an anthraquinone glucoside with the molecular formula C21H20O10 and a molecular weight of 432.3810. Its chemical structure consists of emodin molecules and glucose molecules linked at 1-O sites to form glucosidic bonds, giving it excellent water solubility and bioavailability. The anthraquinone core in the structure is a tricyclic aromatic structure with multiple hydroxyl substituents. Glucosylation modification significantly increases its polarity, with TPSA (topological surface area) reaching 173.98 Ų, indicating strong molecular polarity and favorable water solubility.

In terms of physicochemical properties, the LogP value of emodin-1-O-glucoside is 0.5761, indicating strong hydrophilicity, with a water solubility of about 1.9646, suitable for dissolution and transport in aqueous media. Its low blood-brain barrier permeability suggests that this compound has limited penetration into the central nervous system, which may reduce the occurrence of central nervous system side effects. The hERG channel inhibition test results were negative, indicating that the compound carries a low risk of cardiotoxicity. The Ames test result was 1.2, indicating a low genotoxicity risk and meeting drug safety requirements.

Plant Origins and Extraction Methods

Emodin-1-O-glucoside is mainly found in various Chinese medicinal materials, with Rheum spp. and Frangula being the primary sources. In traditional Chinese medicine, rhubarb (Rheum palmatum) and related varieties, rich in anthraquinone compounds, are widely used for purgation, anti-inflammation, and detoxification treatments. Plants such as Frangula alnus (European rhubarb) also contain large amounts of these glucoside derivatives.

The extraction method typically uses polar solvents such as methanol, water, or ethanol as the extractor, and the crude extract is obtained through hot reflux extraction or ultrasound-assisted extraction. Subsequently, using liquid-liquid separation, silica gel column chromatography, high-performance liquid chromatography (HPLC), and other separation and purification techniques, emodin-1-O-glucoside was further isolated and purified. In recent years, the application of supercritical CO2 extraction and membrane separation technologies has improved extraction efficiency and purity. During extraction, controlling temperature and pH is crucial for maintaining the stability of glucosidic bonds and preventing hydrolysis into emodin free bodies.

Pharmacological activity research

Antiviral activity

Emodin-1-O-glucoside has shown significant potential in antiviral research. Especially in studies of SARS-CoV-2 infection mechanisms, this compound can effectively block the binding of the viral spike protein (S protein) to the host cell's ACE2 receptor, blocking the key step of viral invasion and thereby inhibiting viral replication and transmission. Additionally, its inhibitory effect on casein kinase 2 (CK2) further interferes with signal transduction during viral replication, enhancing antiviral efficacy. Relevant in vitro cell experiments and molecular docking studies support its potential as a candidate drug against COVID-19.

Anti-inflammatory effects

Emodin-1-O-glucoside regulates inflammatory responses through multiple signaling pathways, demonstrating good anti-inflammatory activity. It can inhibit the expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), reducing damage to inflammatory tissues. Mechanismally, it involves downregulation of inflammatory signaling pathways such as NF-κB and MAPK, inhibiting the release of inflammatory mediators and thus exerting protective effects. Animal model studies have shown that this compound can significantly alleviate inflammatory symptoms, suggesting its potential application in chronic inflammatory diseases.

Anti-cancer effects

As a natural product of the anthraquinone class, emodin-1-O-glucoside exhibits antitumor activity in various cancer models, with particularly in-depth research in the field of colon cancer. Its main targets of action include AMPK (PRKAA1), BCL2, STAT3, ABCB1, ALOX5, LCK, TOP1, MAPK1, TNF, and GSK3B, involving cell proliferation, apoptosis, migration, and drug resistance regulation. By activating the AMPK signaling pathway, it promotes energy metabolism imbalance in cancer cells; Downregulate the anti-apoptotic protein BCL2, inducing apoptosis; Inhibits the STAT3 signaling pathway, blocking tumor cell proliferation and immune escape; Additionally, it can reverse the activity of the multidrug resistance-related protein ABCB1, enhancing chemotherapy drug sensitivity. Both in vivo and in vitro experiments have confirmed its effects on inhibiting colon cancer cell proliferation and reducing tumor size.

Metabolic regulation

Emodin-1-O-glucoside, as an effective and selective 11β-HSD1 inhibitor, has IC50s of 186 nM and 86 nM for human and mouse 11β-HSD1, respectively. 11β-HSD1 is a key enzyme for local activation of glucocorticoids and is involved in the development of metabolic syndrome, obesity, and type 2 diabetes. By inhibiting 11β-HSD1, emodin-1-O-glucoside reduces levels of active glucocorticoids in tissues, improving insulin resistance and lipid metabolism disorders. Related studies have shown that this compound can significantly improve metabolic disorders in diet-induced obese mice, reducing body weight, blood sugar, and blood lipid levels, suggesting its application prospects in the treatment of metabolic diseases.

Mechanism of action and molecular targets

The multi-target mechanism of emodin-1-O-glucoside reflects its complex pharmacological characteristics. Its main mechanisms of action include:

1. Blocking viral invasion: By directly binding to the SARS-CoV-2 spike protein or ACE2 receptor, the interaction between the two is blocked, preventing the virus from entering host cells. Molecular docking and cell experiments have shown high affinity for the S protein-ACE2 binding interface.

2. Inhibition of casein kinase 2 (CK2): As an important regulatory factor for various viral replication and cell signaling, CK2's inhibition helps block the viral life cycle and regulate inflammatory responses.

3. Regulating inflammatory signaling pathways: By inhibiting signaling pathways such as NF-κB and MAPK, it reduces the expression of pro-inflammatory factors and alleviates tissue inflammatory damage.

4. Anti-tumor signaling regulation: activates the AMPK pathway, inducing energy metabolism imbalance in cancer cells; Inhibits STAT3 and BCL2, promoting tumor cell apoptosis; Inhibits ABCB1, reversing multidrug resistance; Regulates TOP1 and GSK3B, affecting DNA damage repair and the cell cycle.

5. Selective inhibition of 11β-HSD1: Reduces tissue glucocorticoid activity, improves metabolic disorders, and alleviates obesity and insulin resistance.

These multi-target and multi-pathway mechanisms make emodin-1-O-glucoside highly applicable in antiviral, anti-inflammatory, anticancer, and metabolic disease treatments.

Druggability evaluation and pharmacokinetics

The druggability parameters of emodin-1-O-glucoside indicate that it has a solid foundation for drug development. Although the molecular weight of 432.38 is slightly above the ideal range for traditional oral drugs, its lower LogP value (0.5761) and higher polarity (TPSA 173.98) are beneficial for improving water solubility and bioavailability. The water solubility index of 1.9646 supports its good solubility in the body. The low permeability of the blood-brain barrier reduces the potential risk of toxicity in the central nervous system. The hERG channel is negative for inhibition and the low genotoxicity risk of the Ames test, further supporting its safety.

Pharmacokinetics, current research is limited, but based on its structure, oral administration of emodin-1-O-glucoside may undergo intestinal glucosidase-mediated hydrolysis, releasing active emodin, which is then metabolized by hepatic enzymes. Its glucoside form helps improve intestinal absorption and stability. In the future, further in vivo pharmacokinetic studies are needed to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics, providing a basis for clinical application.

Prospects and outlooks for clinical applications

Emodin-1-O-glucoside, as a versatile natural product, demonstrates broad application potential across multiple disease areas. Its anti-COVID-19 activity provides new drug candidates for the current global public health crisis, especially in blocking viral invasion and replication. Combined with its anti-inflammatory and immunomodulatory effects, it is expected to serve as an adjunct therapy to alleviate the inflammatory storm caused by viral infections.

In tumor treatment, especially colon cancer, emodin-1-O-glucoside regulates tumor cell proliferation and drug resistance mechanisms through multiple targets, demonstrating potential as a novel anticancer drug. Its inhibitory effect on the multidrug resistance protein ABCB1 helps improve the efficacy of existing chemotherapy regimens.

In the field of metabolic diseases, the development of selective 11β-HSD1 inhibitors has long been an important direction in the treatment of diabetes and obesity. Emodin-1-O-glucoside improved its performance in diet-induced obesity models, providing a solid foundation for its clinical translation.

Future research should focus on pharmacokinetic optimization, formulation development, and preclinical safety evaluation. At the same time, combining modern drug design technologies, such as structural optimization and nanocarrier delivery, enhances bioavailability and targeting. The launch of multicenter clinical trials will be a key step in verifying its efficacy and safety.

Conclusion

Emodin-1-O-glucoside, as a natural anthraquinone product with multiple biological activities, shows broad application prospects in antiviral, anti-inflammatory, anticancer, and metabolic disease treatments due to its unique chemical structure and multi-target mechanism. Its excellent druggability parameters and safety evaluation lay the foundation for drug development. In the future, through systematic pharmacological mechanism research, pharmacokinetic optimization, and clinical validation, it is expected that emodin-1-O-glucoside will be developed into a new generation of natural product drugs, contributing new strength to human health.