Synonym name: Pulmatin
Catalogue No.: BP0349
Cas No.: 4839-60-5
Formula: C₂₁H₂₀O₉
Mol Weight: 416.382
Botanical Source: Rheum palmatum (Turkey rhubarb)

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  Chrysophanol 1-glucoside

NMR of  Chrysophanol 1-glucoside

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

Introduction/Overview

Chrysophanol 1-glucoside (CAS No.: 4839-60-5) is a natural anthraquinone compound widely found in various traditional Chinese medicinal materials, especially in plants such as rhubarb (Rheum spp.). As a glycoside derivative of chrysophanol, its molecular structure incorporates glucose units, giving it unique physicochemical properties and biological activity. In recent years, with the deepening development of natural product pharmacology, rhetinol-1-O-glucoside has gradually become a research hotspot due to its potential therapeutic value in tumors, inflammation, and metabolic diseases. Numerous in vitro and in vivo experiments have shown that this compound can effectively inhibit epidermal growth factor (EGF)-induced phosphorylation of epidermal growth factor receptors (EGFR), thereby blocking downstream AKT and mTOR/p70S6K signaling pathways, demonstrating significant antitumor and anti-inflammatory activity.

This paper aims to systematically review the chemical structure and physicochemical properties, plant origins and extraction methods, pharmacological activity, and mechanism of action of rhebinol-1-O-glucoside, and, combined with its druggability parameters, explore its clinical application prospects and future research directions, providing reference and guidance for the field of natural product pharmacology.

Chemical structure and physicochemical properties

Rhein 1-O-glucoside is the 1-O-glucoside form of the anthraquinone compound efanophenol, with a molecular formula of C21H20O10 and a molecular weight of 416.38. Its structural core is the anthraquinone tricyclic backbone, with one hydroxyl group linked to glucose molecules via glycosidic bonds, forming a stable glycosidic bond structure. This structure imparts high polarity and water solubility, with a LogP value of only 0.19, indicating strong hydrophilicity, which facilitates absorption and distribution in the body.

In terms of physicochemical properties, the topological surface area (TPSA) of rhebinol-1-O-glucoside is 164.67 Ų, indicating it has a large number of polar groups, especially hydroxyl and oxygen atoms, capable of forming multiple hydrogen bonds (with 9 hydrogen bond acceptors), which helps bind to biological macromolecule targets. Its molecular structure is stable and shows no significant hepatotoxicity or cardiotoxicity. Both hERG channel inhibition and Ames-induced mutagenic tests were negative, indicating good safety.

Detailed analysis of the molecular structure shows that the glycoside portion not only increases the molecule's water solubility, but may also affect membrane permeability and metabolic stability. Due to low blood-brain barrier permeability (BBB Low), this compound has limited effects on the central nervous system, but this also reduces the risk of central toxicity.

Plant Origins and Extraction Methods

Rhein 1-O-glucoside is mainly found in Rheum spp., especially abundant in traditional Chinese medicinal herbs such as Chinese rhubarb (Rheum palmatum L.) and Rheum officinale Baill. As a traditional Chinese medicinal herb, rhubarb is widely used in clinical applications such as purgative treatment, clearing heat and detoxifying, and promoting blood circulation to remove blood stasis. Its active ingredients are complex, among which anthraquinones are one of the main active components.

The extraction method typically uses solvent extraction combined with chromatography separation technology. Common solvents include ethanol, water, methanol, etc. Reflux extraction or ultrasonic-assisted extraction are often used to improve extraction efficiency. The extract undergoes steps such as concentration, separation, column chromatography (such as silica gel columns and reversed-phase C18 columns), and is finally purified by high-performance liquid chromatography (HPLC) to obtain high-purity rhein 1-O-glucoside.

In recent years, green extraction technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been applied to the extraction of this compound, significantly improving extraction efficiency and purity, reducing the use of organic solvents, and aligning with the modern trend of natural product extraction and environmental protection.

Pharmacological activity research

The pharmacological activity of rhebinol-1-O-glucoside mainly lies in its anti-tumor, anti-inflammatory, and regulation of cellular signaling.

Antitumor activity

Numerous in vitro cell experiments have shown that rhebinol-1-O-glucoside can significantly inhibit the proliferation and migration of various tumor cell lines. Its mechanism mainly involves blocking EGF-induced EGFR phosphorylation, inhibiting downstream AKT and mTOR/p70S6K signaling pathways, thereby suppressing cell cycle progression and inducing apoptosis. For example, in cells of lung, breast, and colorectal cancers, this compound exhibits significant tumor-suppressing effects, reducing cell activity and promoting the expression of apoptosis-related proteins.

Anti-inflammatory activity

Emodol-1-O-glucoside also exhibits good anti-inflammatory activity. By inhibiting activation of the EGFR signaling pathway, it reduces the expression of pro-inflammatory factors such as TNF-α and IL-6, thereby alleviating inflammatory responses. Additionally, its regulation of the NF-κB signaling pathway has been reported, helping to reduce the release of inflammatory mediators and lessen tissue damage.

Other pharmacological effects

Some studies have indicated that this compound has antioxidant activity, can eliminate free radicals, and protect cells from oxidative stress damage. In addition, its potential regulatory effects on metabolic-related diseases such as non-alcoholic fatty liver disease (NAFLD) and diabetes are gradually gaining attention, possibly related to its regulation of the mTOR signaling pathway.

Mechanism of action and molecular targets

The main molecular targets of rhebinol-1-O-glucoside are epidermal growth factor receptors (EGFR) and their downstream signaling pathways. EGFR is a receptor-tyrosine kinase that is widely involved in regulating cell proliferation, differentiation, and survival. After EGF binds to EGFR, it promotes phosphorylation of tyrosine residues, activating multiple signaling pathways including PI3K/AKT and mTOR/p70S6K.

This compound blocks signal transduction by inhibiting EGF-induced EGFR phosphorylation, leading to decreased AKT and mTOR/p70S6K activity, inhibiting cell proliferation and promoting apoptosis. As a key cell survival signaling molecule, AKT's inhibition helps to alleviate the suppression of the apoptosis pathway. The mTOR/p70S6K signaling pathway regulates protein synthesis and cell growth, and its downregulation helps suppress tumor cell metabolic activity.

Additionally, glycoside structures may enhance the molecule's water solubility and targeting, improving binding affinity and selectivity with receptors. Some studies also suggest that rhebinol-1-O-glucoside may affect other signaling pathways such as NF-κB and MAPK, further exerting anti-inflammatory and antitumor effects, though the specific mechanisms still require further exploration.

Druggability evaluation and pharmacokinetics

From the perspective of druggability, efanophenol-1-O-glucoside demonstrated good safety and drug metabolism characteristics.

Safety evaluation

According to existing data, this compound shows no significant hepatotoxicity or cardiotoxicity, and the hERG channel inhibition test was negative, suggesting a low risk of arrhythmias. Ames-induced mutagenic tests were negative, indicating a low genotoxicity risk. These characteristics lay a solid foundation for its clinical development.

Pharmacokinetic characteristics

The LogP value of rhebinol-1-O-glucoside is 0.19, indicating strong hydrophilicity, which facilitates dissolution and distribution in plasma, but may limit its cell membrane penetration ability. A higher TPSA (164.67 Ų) and a higher number of hydrogen bond acceptors (9) also support its strong water solubility, but may affect oral bioavailability.

The low permeability of the blood-brain barrier suggests its limited distribution in the central nervous system, making it suitable for non-central target diseases. The metabolic pathways in the body are not yet fully understood, but glycoside structures may be hydrolyzed by gut microbes or liver enzyme systems, releasing active emodol, which affects the duration of its efficacy and metabolic stability.

In the future, in vivo pharmacokinetic studies are needed to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics, providing a basis for dosage formulation design and administration regimen optimization.

Prospects and outlooks for clinical applications

Efanophenol-1-O-glucoside has broad application prospects in tumor treatment due to its significant inhibition of EGFR and downstream signaling pathway activity. Abnormal activation of the EGFR signaling pathway is a key driver of the development of various tumors, and several EGFR-targeting drugs have already been approved for clinical use. As a natural product, this compound boasts a novel structure and high safety, making it a promising candidate for novel anti-tumor drugs.

Moreover, its anti-inflammatory properties give it potential therapeutic value in chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Combined with its regulation of the mTOR signaling pathway, future applications in metabolic diseases such as fatty liver and diabetes can be explored.

Looking ahead, research in the following areas needs to be strengthened:

1. In-depth mechanism research: clarifying its interactions with EGFR and other signaling pathways, revealing the mechanism by which glycoside structure affects activity.
2. Pharmacokinetic and toxicological assessment: Systematic evaluation of in vivo behavior and long-term safety.
3. Structural optimization and derivative development: Chemical modification enhances bioavailability and targetability.
4. Preclinical and clinical research: Conduct animal models and clinical trials to verify efficacy and safety.

By combining modern drug design with natural product development technologies, rhenophenol-1-O-glucoside is expected to become a multi-target, multifunctional innovative drug, offering new strategies for the treatment of related diseases.

Conclusion

Efanophenol-1-O-glucoside, as a natural anthraquinone compound, demonstrates remarkable antitumor and anti-inflammatory activities due to its unique chemical structure and excellent physicochemical properties. It works by inhibiting EGF-induced EGFR phosphorylation and downstream AKT and mTOR/p70S6K signaling pathways, with a well-defined mechanism and good safety. Although research on its metabolism and clinical application in vivo is still in its early stages, its potential for natural drug development cannot be ignored.

In the future, multidisciplinary research integrating modern pharmacology, pharmacokinetics, and medicinal chemistry will promote the clinical application of rhebinol-1-O-glucoside, support the development of new, efficient, and low-toxicity natural drugs, and provide new ideas and options for treating major diseases such as tumors and inflammation.