Synonym name: Luteolin 5-glucoside; Galuteolin
Catalogue No.: BP0898
Cas No.: 20344-46-1
Formula: C₂₁H₂₀O₁₁
Mol Weight: 448.38
Botanical Source: Galega officinalis and other plant spp

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 Luteolin-5-O-glucoside

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

Introduction/Overview

Natural products, as important resources for drug discovery, have long held a central position in pharmacological research and new drug development due to their structural diversity and broad biological activity. Flavonoids, as an important class of plant secondary metabolites, have become a hot topic in natural product pharmacology research due to their remarkable antioxidant, anti-inflammatory, antitumor, and neuroprotective activities. Luteolin-5-O-glucoside (CAS No.: 20344-46-1) is a flavonoid glycoside mainly isolated from Cirsium maackii, a plant in the Asteraceae family. In recent years, more and more studies have shown that this compound has significant anti-inflammatory activity, can regulate various inflammation-related molecular targets, and inhibit the formation of inflammatory mediators, thus demonstrating potential application value in the prevention and treatment of inflammatory diseases.

This paper systematically reviews the chemical structure and physicochemical properties, plant origin, and extraction methods of luteolin-5-O-glucoside, focusing on its pharmacological activity and mechanism of action, analyzing its pharmacokinetic characteristics in combination with druggability parameters, and finally looking ahead to its clinical application prospects, providing a theoretical basis and research direction for drug development of this natural product.

Chemical structure and physicochemical properties

luteolin-5-O-glucoside belongs to the flavonoid class of flavonoid compounds, with a molecular formula of C21H20O11 and a molecular weight of 448.38. Its structure is formed by the flavonoid nucleotide luteolin and glucose connected by an O-glycosidic bond formed by the 5-hydroxyl group. The basic framework of luteolin consists of two aromatic rings (A and B rings) and a central oxygen heterocycle (C ring). Glucosylation modification gives it higher water solubility and bioactivity regulatory potential.

In terms of physicochemical properties, luteolin-5-O-glucoside has a LogP value of -0.1856, indicating strong hydrophilicity. Water solubility is 1.6749 (unit not specified, but generally mg/mL or mol/L), and its polarized surface area (TPSA) is 190.28 Ų, indicating high polarity and the number of hydrogen bond donors/acceptors, which may affect cell membrane permeability and bioavailability. The blood-brain barrier has low permeability, suggesting limited function in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0.6, indicating a low genotoxicity risk and a solid safety foundation.

Plant Origins and Extraction Methods

Luteolin-5-O-glucoside is mainly found in the Asteraceae plant Cirsium maackii. Cirsium plants are widely distributed in temperate regions of Asia and have traditionally been used to treat inflammation, liver diseases, and immune-related disorders. This compound is typically extracted using solvent extraction combined with chromatography separation technology.

The specific extraction steps include: collecting the aboveground part of Cirsium maackii, drying and crushing it, then reflux extraction using methanol or ethanol aqueous solution (such as 70% ethanol). The extract is concentrated and fractionated, then purified using silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC) techniques, ultimately obtaining high-purity luteolin-5-O-glucoside. In recent years, green and efficient technologies such as ultrasound-assisted extraction and microwave-assisted extraction have also been applied to extract this compound, improving extraction efficiency and purity.

Pharmacological activity research

Anti-inflammatory activity

The anti-inflammatory effect of luteolin-5-O-glucoside is one of its most notable pharmacological activities. In vitro experiments showed that this compound significantly inhibited nitric oxide (NO) production in macrophages induced by lipopolysaccharides (LPS), reduced excessive production of oxygen free radicals (ROS), and alleviated oxidative stress responses. Its targets include induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), both of which are key enzymes in inflammatory responses and participate in the synthesis of inflammatory mediators.

Additionally, luteolin-5-O-glucoside can inhibit the expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), regulate the nuclear factor κB (NF-κB) signaling pathway, and reduce inflammatory responses. Based on its regulatory effect on macrophages, luteolin-5-O-glucoside demonstrates good protective effects in various models of inflammatory diseases.

Antioxidant activity

luteolin-5-O-glucoside reduces oxidative stress damage and protects cells from oxidative damage by inhibiting peroxide free radicals (t-BHP-induced ROS production). Its antioxidant capacity is closely related to the electron supply capacity of hydroxyl groups in its flavonoid structure. Glucosylation modification further enhances its water solubility, facilitating its distribution in the body and the effect of antioxidant effects.

Other potential activities

Although current research mainly focuses on anti-inflammatory and antioxidant effects, luteolin-5-O-glucoside is gradually gaining attention for its potential in regulating apoptosis, immune regulation, and neuroprotection. Its regulation of signal transduction molecules such as STAT3, CASP1, TRPV1, and TRPA1 suggests its potential role in complex diseases such as tumors and neuropathy, warranting further research.

Mechanism of action and molecular targets

The anti-inflammatory mechanism of luteolin-5-O-glucoside is mainly achieved through multi-target and multi-pathway coordinated regulation. Its key targets and signaling pathways include:

• iNOS (NOS2) and COX-2 (PTGS2): Inhibit the expression of these two enzymes, reduce the production of NO and prostaglandin E2 (PGE2), and lower the release of inflammatory mediators.
• NF-κB signaling pathway (NFKB1): Inhibits NF-κB activation, blocks transcription of pro-inflammatory genes, and reduces inflammatory responses.
• Pro-inflammatory cytokines TNF-α and IL-6: Downregulate the expression of these cytokines and inhibit the inflammatory cascade.
• STAT3 signaling pathway: regulates STAT3 phosphorylation, affecting cell proliferation, apoptosis, and inflammatory responses.
• Inflammation-related ion channels TRPV1 and TRPA1: regulate the activity of these channels, alleviating inflammation-related pain and neural responses.
• CASP1 (caspase 1): inhibits its activity, blocks the activation of inflammasomes, and reduces the release of the pro-inflammatory factor IL-1β.

Through these multi-target effects, luteolin-5-O-glucoside not only inhibits the production of inflammatory mediators but also regulates immune cell function, reduces tissue damage, and demonstrates its potential as a natural anti-inflammatory drug.

Druggability evaluation and pharmacokinetics

The druggability parameters of luteolin-5-O-glucoside show that it has certain advantages and limitations. The molecular weight is 448.38, which fits the molecular weight range of most oral small molecule drugs. Its LogP value is -0.1856, indicating strong hydrophilicity, which facilitates dissolution in the blood, but may limit passive diffusion and absorption of cell membranes. A higher TPSA (190.28 Ų) suggests greater polarity, which may affect oral bioavailability and tissue permeability.

Good water solubility, which is beneficial for formulation development and distribution in vivo. The low permeability of the blood-brain barrier suggests limited application in central nervous system diseases, but also reduces the risk of central toxicity. hERG channel inhibition was negative, indicating higher cardiac safety. Ames test results are low, and the genotoxicity risk is small.

Currently, there is limited pharmacokinetic research on luteolin-5-O-glucoside, but preliminary speculation suggests that its glucoside structure may be hydrolyzed in the gastrointestinal tract to luteolin, affecting its biological activity and metabolic fate. In the future, systematic studies are needed on its absorption, distribution, metabolism, and excretion (ADME) characteristics to guide clinical application and formulation design.

Prospects and outlooks for clinical applications

Given the significant anti-inflammatory and antioxidant activity of luteolin-5-O-glucoside, its application prospects in various inflammation-related diseases are broad. Including but not limited to:

• Autoimmune diseases: such as rheumatoid arthritis and systemic lupus erythematosus, which regulate immune responses and reduce inflammatory damage.
• Chronic inflammatory diseases: such as inflammatory bowel disease and chronic obstructive pulmonary disease (COPD), which alleviate chronic inflammatory states.
• Metabolic diseases: In diabetes and its complications, it reduces inflammation and oxidative stress, protecting tissue function.
• Neuroinflammation and pain management: By modulating TRPV1 and TRPA1 plasma channels, it alleviates pain related to neuroinflammation.
• Tumor adjuvant therapy: By regulating STAT3 and inflammatory pathways, it suppresses pro-inflammatory responses in the tumor microenvironment, adjuvanting anti-tumor therapy.

Future research should focus on in vivo pharmacokinetics, toxicological evaluation, and preclinical animal model validation of luteolin-5-O-glucoside, combined with modern drug formulation technologies to enhance its bioavailability and targetability. In addition, structural modification and derivative development are also effective strategies to enhance efficacy and druggability.

Conclusion

As a natural flavonoid glycoside derived from Cirsium maackii, luteolin-5-O-glucoside shows promising potential in the prevention and treatment of inflammation-related diseases due to its significant anti-inflammatory and antioxidant activities. Its multi-target and multi-pathway mechanism of action provides new ideas for the development of natural product anti-inflammatory drugs. Although research on its in vivo pharmacokinetics and clinical applications is still in its early stages, its favorable safety and druggability parameters lay the foundation for subsequent studies. In the future, through systematic pharmacological and pharmacokinetic studies, combined with modern drug design and formulation technologies, it is expected to promote the clinical translation of luteolin-5-O-glucoside into clinical practice, making it an important candidate for natural anti-inflammatory drugs.