Product name: Methyl syringate-4-O-β-D-glucopyranoside
Synonym name:
Catalogue No.: BP2403
Cas No.: 586398-39-2
Formula: C₁₆H₂₂O₁₀
Mol Weight: 374.342
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.

NMR of Methyl syringate-4-O-β-D-glucopyranoside

HPLC of Methyl syringate-4-O-β-D-glucopyranoside

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

Introduction/Overview

Natural products, as an important source of drug discovery, play an irreplaceable role in the long history of human struggle against diseases. From crude extracts of traditional herbs to purified monomers in modern medicinal chemistry, the diverse types and structures of secondary metabolites in nature continue to provide valuable lead compounds for the development of innovative drugs. Among numerous natural products, phenolic acids and their glycosides have attracted much attention due to their wide range of biological activities. Methyl syringate-4-O - β - D-glucopyranoside (MSG), as a derivative of syringic acid, is a component with unique pharmacological activity isolated and identified from various medicinal plants in recent years. Its structure is composed of a methyl syringic acid core connected to a molecule of glucose through a β - glycosidic bond, which endows it with physicochemical and biological properties distinct from its aglycone syringic acid.

Oral disease, especially caries and periodontal disease, is one of the most common chronic infectious diseases worldwide, which seriously affects the quality of life and general health of human beings. Oral pathogenic bacteria, such as Streptococcus mutans（Streptococcus mutans）Porphyromonas gingivalis（Porphyromonas gingivalis）And Candida albicans（Candida albicans）Waiting is the main pathogen of these diseases. Traditional antibacterial therapies, such as the use of antibiotics and chemically synthesized preservatives (such as chlorhexidine), although effective, long-term use may lead to dysbiosis, drug resistance, and local side effects (such as tooth discoloration and taste changes). Therefore, the search for efficient, low toxicity, and resistant natural antibacterial active ingredients has become a research hotspot in the field of oral disease prevention and treatment. MSG has gradually entered the field of researchers due to its inhibitory activity against various oral pathogenic bacteria, as well as its potential multiple pharmacological effects such as anti-inflammatory and antioxidant effects.

This article aims to provide a systematic professional review of the natural product methyl syringate glucoside (MSG). The article will delve into its chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity research, mechanism of action and molecular targets, evaluation of drug properties and pharmacokinetic characteristics, as well as clinical application prospects, in order to provide comprehensive scientific basis and theoretical reference for the subsequent research and development of this natural product.

Chemical structure and physicochemical properties

The chemical structure of methyl syringate glucoside (MSG) exhibits typical phenolic glycoside characteristics. Its core structure is methyl syringate, which is 3,5-dimethoxy-4-hydroxybenzoic acid methyl ester. A molecule of D-glucopyranose is connected to the 4-hydroxy group of methyl syringate through a β - glycosidic bond. Therefore, its systematic name is usually 4-hydroxy-3,5-dimethoxybenzoic acid-4-O - β - D-glucopyranose. The chemical formula of this molecule is C ₁₆ H ₂ O ₁₀, and the molecular weight is 374.3420 g/mol.

From the perspective of physicochemical properties, the sugar moiety of MSG endows it with significant water solubility. The calculated LogP value is -0.4474, indicating that the compound has hydrophilicity and is not easily able to penetrate the lipid bilayer of biological membranes. Its topological polar surface area (TPSA) is 144.1400 Å ², much higher than the recommended threshold for oral medications (<140 Å ²), which further confirms its high polarity and strong water solubility. The solubility parameter is 34.4264 mg/mL, which belongs to highly water-soluble compounds. Although this high water solubility is beneficial for its dissolution and distribution in aqueous environments such as saliva and blood, it may also limit its ability to passively diffuse through cell membranes. In addition, MSG has a moderate molecular weight, meeting the basic requirements for molecular weight in Lipinski's Rule of Five (<500 Da), but its high polarity (LogP<0) and TPSA value suggest that it may face challenges in oral absorption. In terms of spectroscopic characteristics, UV absorption spectra typically have characteristic absorption peaks at around 270-280 nm, attributed to the π→π * transition of the benzene ring. Infrared spectroscopy can observe characteristic absorption peaks of hydroxyl (~3400 cm ⁻¹), carbonyl (~1700 cm ⁻¹), and glycosidic bond (C-O-C). Nuclear magnetic resonance spectroscopy (¹ H-NMR and ¹ ³ C-NMR) is a key means of identifying its structure, where the coupling constant (J value) of the sugar end proton (H-1 ') is typically 7-8 Hz, confirming the configuration of the β - glycosidic bond.

Plant sources and extraction methods

Methyl syringate glucoside is not widely present in all plants, but is isolated from specific medicinal plants. The main sources of current literature reports include:

1. Syringa plants（Syzygium aromaticum）As the origin of its name, MSG is one of the important active ingredients in cloves (a commonly used spice and traditional Chinese medicine). Extracting MSG from dried flower buds of cloves is a classic way to obtain MSG.
2. Peony plants（Paeonia spp.）For example, from red peony root（Paeonia lactiflora）Or peonies（Paeonia suffruticosa）MSG has been successfully isolated from the root bark. Peony plants are rich in various phenolic and glycoside compounds, and MSG is an important component of their chemical composition spectrum.
3. Other plants In the family Crassulaceae plants (such as Lagerstroemia speciosa）Plants of the Rubiaceae family (such as Rubia cordifolia）MSG has also been reported in some ferns. This indicates that the compound has a certain distribution in the plant kingdom, but its content is usually low.

For the extraction of MSG, classical phytochemical methods are usually used, with the core being the utilization of its high polarity. The main process includes:

1. Raw material pretreatment Crush dry plant materials (such as clove buds and peony root bark) to an appropriate particle size.
2. Solvent extraction Due to its good water solubility, MSG is often extracted using polar solvents. The most commonly used solvents are methanol, ethanol, or their aqueous solutions (such as 50% -80% ethanol). The extraction methods include cold soaking, percolation, or heating reflux. The heating reflux efficiency is high, but attention should be paid to controlling the temperature and time to avoid hydrolysis of glycosidic bonds.
3. Preliminary separation The extract is concentrated under reduced pressure to obtain a paste. Disperse the extract in water and perform liquid-liquid extraction using solvents of different polarities such as petroleum ether, ethyl acetate, and n-butanol in sequence. MSG is mainly enriched in the n-butanol extraction layer or water layer due to its polarity.
4. chromatographic separation This is a crucial step in purifying MSG. Common chromatographic techniques include:
   • Macroporous adsorption resin column chromatography Resin such as D101 and AB-8 can effectively remove impurities such as sugars and enrich target components by washing with a water ethanol gradient.
   • Silica gel column chromatography Use polar elution systems such as chloroform methanol water or ethyl acetate methanol water for separation.
   • Reverse phase column chromatography For example, using an ODS (C18) column, gradient elution with methanol water or acetonitrile water system yields better separation efficiency.
   • Preparation type high performance liquid chromatography (Prep HPLC)For the preparation of high purity (>98%) MSG samples, Prep HPLC is the ultimate and most effective method.
5. Structural Identification The purified monomer compound was structurally confirmed by spectroscopic methods (NMR, MS, UV, IR) and compared with literature data.

Pharmacological activity research

In recent years, research on the pharmacological activity of MSG has gradually deepened, mainly focusing on the following aspects:

1. Anti oral pathogenic bacteria activity This is the pharmacological activity of MSG that has received the most attention. Research has shown that MSG has inhibitory effects on various common oral pathogens.

   • Regarding Streptococcus mutans（S. mutans）Streptococcus mutans is the main pathogenic bacterium of dental caries. MSG can effectively inhibit its growth in a planktonic state and exhibits a dose-dependent effect. More importantly, MSG can significantly inhibit the formation of Streptococcus mutans biofilm at sub MIC concentrations, which is the key to its anti caries activity. Biofilm is a three-dimensional structure formed by bacteria on the surface of teeth, which can greatly enhance bacterial drug resistance and resistance to host immune defense. MSG reduces the pathogenic potential of bacteria by interfering with the formation of biofilms.
   • Porphyromonas gingivalis（P. gingivalis）Porphyromonas gingivalis is the main pathogen of chronic periodontitis. MSG also exhibits inhibitory effects on its growth and can suppress the activity of key virulence factors, such as gingival proteases.
   • Regarding Candida albicans（C. albicans）Candida albicans is the main pathogen of oral candidiasis and often co causes with other bacteria. MSG exhibits certain inhibitory activity against planktonic cells and biofilms of Candida albicans.
   • For other oral bacteria The study also found that MSG has an effect on Fusobacterium nucleatum（Fusobacterium nucleatum）Intermediate Prevotella（Prevotella intermedia）Periodontal pathogenic bacteria also have inhibitory effects.

2. anti-inflammatory activity In addition to its direct antibacterial effect, MSG also exhibits anti-inflammatory potential. In the macrophage model stimulated by lipopolysaccharide (LPS), MSG can significantly reduce the production of pro-inflammatory cytokines such as tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6), and interleukin-1 β (IL-1 β). This activity is particularly important for the treatment of inflammatory diseases such as periodontitis, as the destruction of periodontal tissue is largely mediated by the host's excessive inflammatory response to bacterial infections.

3. antioxidant activity The phenolic hydroxyl structure of MSG endows it with the ability to scavenge free radicals. In vitro DPPH, ABTS and other free radical scavenging experiments showed that MSG has certain antioxidant activity. Although its activity may be weaker than some potent antioxidants such as vitamin C, as a glycoside, it has better stability and water solubility, and may exert sustained antioxidant protection under physiological conditions, reducing oxidative stress damage to oral tissues.

4. Other activities: The preliminary study also suggests that MSG may have a slight analgesic effect and inhibit the activity of some enzymes (such as α - glucosidase), suggesting its potential value in the management of diabetes and its complications, but the research on these aspects is not yet in-depth.

Mechanism of action and molecular targets

The pharmacological activity of MSG, especially its anti oral pathogenic effect, involves multiple molecular targets and signaling pathways. According to the information you provided, its potential targets include GYRA, DHFR, FOLA, GYRB, PBP2, ERG, GTFB, and FTFA. These targets cover multiple key life processes such as bacterial DNA replication, folate metabolism, cell wall synthesis, cell membrane function, and extracellular polysaccharide synthesis.

1. Inhibition of DNA replication and folate metabolism：

   • GYRA and GYRB Encode the A and B subunits of DNA gyrase respectively. DNA gyrase is a type II topoisomerase unique to bacteria, responsible for introducing negative supercoils during DNA replication to alleviate the twisting pressure on DNA strands. Inhibiting the enzyme activity will result in hindered DNA replication, thereby inhibiting bacterial growth. MSG may interfere with its enzymatic activity by binding to GYRA or GYRB.
   • DHFR and FOLA Dihydrofolate reductase (DHFR) and dihydrofolate synthase (FOLA) are key enzymes in the bacterial folate biosynthesis pathway. Folic acid is an essential cofactor for the synthesis of purines, pyrimidines, and amino acids. Inhibiting these enzymes will block the synthesis of folate, thereby affecting the production of nucleic acids and proteins, and exerting antibacterial effects. MSG may act as a folate analog or interfere with this pathway through other means.

2. Destruction of cell walls and membranes：

   • PBP2 Penicillin binding protein 2 (PBP2) is a transpeptidase involved in the synthesis of peptidoglycans in bacterial cell walls. Inhibiting PBP2 can damage the integrity of the cell wall, leading to bacterial cell lysis. MSG may interfere with its transpeptidase activity by binding to PBP2.
   • ERG Ergosterol is a unique sterol component of fungal cell membranes, which is crucial for maintaining membrane fluidity and integrity. ERG targets typically refer to enzymes involved in ergosterol biosynthesis, such as C14 demethylase. MSG may exert antifungal activity (such as against Candida albicans) by inhibiting the ERG pathway, disrupting the structure and function of fungal cell membranes.

3. Inhibition of virulence factors and biofilm formation：

   • GTFB and FTFA These two targets are closely related to the cariogenic properties of Streptococcus mutans. GTFB (glucosyltransferase B) and FTFA (fructosyltransferase) are key enzymes for bacterial synthesis of extracellular polysaccharides (EPS). EPS is the main component of dental plaque biofilm matrix, which mediates the adhesion and aggregation of bacteria on the surface of teeth, and provides nutrition and shelter for bacteria. MSG can significantly inhibit the activity of GTFB and FTFA at sub inhibitory concentrations, thereby reducing the synthesis of insoluble pectin and pectin, effectively preventing the formation and maturation of biofilms. This is a significant advantage of MSG compared to traditional fungicides, as it does not directly kill bacteria, but rather reduces their pathogenicity by "disarming them", theoretically making it less likely to induce drug resistance.

In summary, the mechanism of action of MSG is multi-target and multi pathway. It can directly inhibit bacterial growth by acting on targets such as GYRA/DHFR, inhibit bacterial virulence factors by acting on targets such as GTFB/FTFA, and regulate host responses through anti-inflammatory and antioxidant activities. This multi-target mode of action is its core advantage as a natural candidate for oral infections.

Evaluation of drug properties and pharmacokinetics

Based on the pharmacological parameters you provided, a preliminary evaluation of the drug like properties of MSG can be conducted.

• Analysis of drug properties：
  • Molecular weight (374.34 Da)Meets the requirement of<500 Da.
  • LogP (-0.4474)Far below 5, indicating strong hydrophilicity. This is beneficial for dissolution and distribution in aqueous environments, but not conducive to passive transmembrane absorption.
  • TPSA (144.14 Ų)Exceeding 140 Å ² suggests that oral absorption may be poor, as highly polar molecules have difficulty penetrating the lipid bilayer of intestinal epithelial cell membranes.
  • Water solubility (34.43 mg/mL): Excellent, which solves the problem of poor water solubility of many candidate drugs and is conducive to the development of preparations (such as mouthwash and oral gel).
  • Blood-brain barrier (BBB) penetrability: Low. This is an advantageous feature because the main application area of MSG is in the oral cavity, rather than the central nervous system. Low BBB penetration can reduce the potential risk of neurotoxicity.
  • HERG inhibition: No. This indicates a low risk of causing prolonged QT interval and arrhythmia in the heart, which is an important safety indicator.
  • Ames test (0.0)The result is negative, indicating that it does not have mutagenicity and has a low risk of genetic toxicity.

Overall, the pharmacological characteristics of MSG exhibit a double-edged sword effect. Its high water solubility, low hERG inhibition risk, and non mutagenicity are significant advantages. However, its high polarity (low LogP, high TPSA) is the main obstacle to its oral bioavailability. Therefore, MSG may not be suitable for development as a traditional oral systemic administration formulation, but rather as a local administration formulation.

• Pharmacokinetic characteristics (speculated)：
  • absorb Poor oral absorption and possibly low bioavailability. Sublingual, oral mucosal or local administration (such as mouthwash, application) may be a better route of administration. After local administration, MSG can remain on the surface of the oral mucosa or in the saliva environment, directly acting on the target (oral pathogenic bacteria), avoiding bottlenecks in systemic absorption.
  • distribution Due to its high polarity, MSG is mainly distributed in extracellular fluid and body fluids, making it difficult to enter cells. This precisely meets its demand for anti oral extracellular pathogens, such as bacteria in biofilms.
  • Metabolism As a glycoside, MSG may be hydrolyzed by microorganisms or host enzymes (such as β - glucosidase) in the intestine (after oral administration) or oral cavity, releasing the aglycone methyl syringate. Glycosides may have different pharmacological activities and pharmacokinetic behaviors. Therefore, MSG may be a prodrug whose active part or all is mediated by aglycones or metabolites.
  • excretion Polarized MSG and its metabolites are mainly excreted through the kidneys in their original form or in the form of conjugates.

Clinical application prospects and prospects

Based on the unique pharmacological activity and good safety characteristics of MSG, its application prospects in the field of oral health are very broad.

1. New anti caries and periodontal disease drugs The multi-target mechanism of action of MSG, especially its ability to inhibit biofilm formation, makes it an ideal lead compound for developing novel anti caries and periodontal disease drugs. It can be developed into:

   • mouthwash As a daily oral care product, it is used to inhibit plaque formation, prevent dental caries and gingivitis.
   • Toothpaste Additives Add it to toothpaste and release it during brushing, exerting a sustained anti biofilm effect.
   • Oral gel or film Used for local administration in periodontal pockets to treat periodontitis, directly targeting deep-seated pathogenic bacteria such as Porphyromonas gingivalis.
   • Root canal flushing agent Used for root canal treatment, it kills stubborn bacteria and fungi in the root canal and improves the success rate of treatment.

2. Anti oral candidiasis The activity of MSG against Candida albicans makes it potential for the treatment of fungal infections such as dental stomatitis and thrush, especially strains that develop resistance to traditional antifungal drugs such as fluconazole.

3. Oral mucosal protectant Combining its anti-inflammatory and antioxidant activities, MSG can be used as an adjuvant therapy for inflammatory diseases such as oral ulcers and oral lichen planus, reducing pain and promoting healing.

4. Synergistic effects with other drugs The combination of MSG with existing antibiotics (such as chlorhexidine, fluoride) or natural products (such as tea polyphenols) may produce synergistic effects, thereby reducing effective concentrations, minimizing side effects, and reducing the risk of drug resistance.

Future research directions：

• In depth mechanism research Using techniques such as molecular docking and surface plasmon resonance (SPR), verify the direct binding mode of MSG to targets such as GYRA, DHFR, and GTFB, and elucidate its precise molecular mechanism.
• Structure Activity Relationship (SAR) Study Synthesize MSG analogs, such as changing the type of sugar group, modifying substituents on the benzene ring, etc., explore the effect of structural changes on activity, and search for derivatives with stronger activity and higher selectivity.
• Pharmaceutical research: Develop dosage forms suitable for local oral administration, such as thermosensitive gel, nano emulsion, liposome, etc., to improve the retention time and bioavailability of MSG in the oral cavity, and achieve sustained and controlled release.
• In vivo efficacy and safety evaluation Establish animal models of oral infections (such as rat dental caries model and mouse periodontitis model), and systematically evaluate the in vivo efficacy, pharmacokinetic characteristics, and long-term toxicity of MSG.
• Clinical translational research After completing sufficient preclinical research, conduct small-scale human clinical trials to verify its safety and initial efficacy in healthy volunteers and patients.

Conclusion

Methyl syringate glucoside (MSG), as a natural phenolic acid glycoside derived from traditional medicinal plants, has shown remarkable potential in the field of oral disease prevention and treatment due to its unique chemical structure and multi-target pharmacological activity. It can not only directly inhibit the growth of various oral pathogenic bacteria, but also effectively inhibit the formation of biofilms by interfering with the synthesis of key virulence factors - extracellular polysaccharides. This mode of action is particularly valuable in addressing the increasingly severe problem of bacterial resistance. Meanwhile, its good water solubility, low toxicity (no hERG inhibition, Ames test negative), as well as anti-inflammatory, antioxidant and other auxiliary activities further enhance its attractiveness as a candidate drug.

Although MSG has the limitation of low bioavailability in oral systemic administration, this provides an opportunity for its application in the field of oral local treatment. By developing suitable local administration formulations, MSG is expected to become a new generation of safe, efficient, and resistant oral care products or therapeutic drugs. Future research should focus on the in-depth elucidation of its mechanism of action, systematic exploration of structure-activity relationships, and the establishment of clinical translation pathways. We have reason to believe that with the continuous deepening of research, methyl syringate glucoside, a gift from nature, will play a greater value in maintaining human oral health and even overall health.