Introduction/Overview
Apigenin-7-O - (2G-rhamnosyl) gentiobinoside is a natural flavonoid glycoside compound that has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and multi-target regulatory properties. This compound exhibits significant biological activity, particularly in the prevention and treatment of metabolic diseases such as obesity, demonstrating potential therapeutic value. With the global prevalence of obesity and its related metabolic syndrome, finding safe and effective natural products has become an important direction for drug development. This article provides a systematic review of the chemical structure, plant origin, pharmacological activity, mechanism of action, pharmacological evaluation, and clinical application prospects of apigenin 7-O-rhamnoside. The aim is to provide theoretical basis and reference for related research.
Chemical structure and physicochemical properties
Apigenin 7-O-rhamnose gentiopicroside is a flavonoid glycoside with a molecular formula of C33H40O19 and a molecular weight of 732.65 Da. Its core structure is apigenin, which is connected to a disaccharide chain consisting of rhamnose and gentiobiose through an O-glycosidic bond via a 7-hydroxyl group. This structure endows it with high polarity and abundant hydrogen bond acceptors, with a hydrogen bond acceptor count of up to 19, greatly affecting its solubility and bioavailability.
In terms of physical and chemical properties, the LogP value of apigenin 7-O-rhamnosus gentiopicroside is -3.5, indicating strong hydrophilicity and low penetration ability in lipid soluble environments. Its topological polar surface area (TPSA) is 300 Å ², indicating that its molecular surface polarity is high, which may limit its passive diffusion through the cell membrane. In addition, the compound has low blood-brain barrier permeability, negative liver toxicity, cardiac toxicity, and hERG channel inhibition. The Ames mutagenicity test also showed no mutagenic risk, indicating its good safety.
Plant sources and extraction methods
Celericin-7-O-rhamnose gentiopicroside is mainly found in certain medicinal plants, especially in plants of the celery genus and Gentianaceae family that have traditional medicinal value. Related literature reports that its content is relatively high in Gentiana spp., Apium graveolens, and other flavonoid rich plants. The compound is mainly distributed in the leaves and rhizomes of plants.
The extraction process usually uses organic solvent extraction combined with column chromatography separation technology. The specific process includes:
1. Use a 70% -80% methanol or ethanol aqueous solution for reflux extraction to ensure the dissolution rate of flavonoid glycosides;
2. Remove the solvent by vacuum concentration to obtain a crude extract;
3. Use silica gel column chromatography or reverse phase C18 column for separation and purification;
4. Finally, the purity and structural identification were confirmed by high-performance liquid chromatography (HPLC).
In recent years, ultrasound assisted extraction (UAE) and microwave-assisted extraction (MAE) technologies have also been applied to improve the extraction efficiency and purity of the compound, reduce energy consumption and extraction time.
Pharmacological activity research
The pharmacological activity research of apigenin 7-O-rhamnosus gentiopicroside focuses on its regulatory effect on metabolic diseases, especially obesity. Both in vitro cell models and in vivo animal experiments have shown that the compound has significant anti obesity and metabolic regulatory effects.
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Anti obesity effect
This compound can effectively inhibit the differentiation and lipid accumulation of adipocytes, and reduce the inflammatory response of adipose tissue. By regulating the expression of genes related to fat metabolism, promoting fatty acid oxidation and inhibiting fat production. Animal experiments have shown that in obese mice induced by a high-fat diet containing apigenin 7-O-rhamnoside, weight gain is significantly slowed down, adipose tissue weight is reduced, and blood lipid levels are improved.
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Anti inflammatory and antioxidant effects
Obesity often accompanies chronic low-grade inflammation, and apigenin 7-O-rhamnoside reduces adipose tissue inflammation by inhibiting the expression of inflammatory factors such as TNF - α and IL-6. In addition, its flavonoid skeleton endows it with strong antioxidant capacity, which can clear free radicals and alleviate oxidative stress damage.
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Regulating energy metabolism
This compound can activate the AMPK signaling pathway, promote energy metabolism and fatty acid oxidation, improve insulin sensitivity, and has potential hypoglycemic effects.
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Other potential activities
Although current research mainly focuses on metabolic diseases, preliminary data suggests that it may also have certain activities in neuroprotection, anti-tumor and other fields, which is worth further exploration.
Mechanism of action and molecular targets
The mechanism of action of apigenin 7-O-rhamnosus gentiopicroside involves multiple molecular targets, reflecting its multi-target and multi pathway regulatory characteristics. The main targets and their functions are as follows:
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AMPK（PRKAA1）
AMP activated protein kinase (AMPK) is a key regulatory factor in cellular energy metabolism. Celericin-7-O-rhamnoside promotes fatty acid oxidation, inhibits fat synthesis, and improves energy metabolism imbalance by activating AMPK.
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PTPN1 (protein tyrosine phosphatase 1B)
PTPN1 is a negative regulator of the insulin signaling pathway, and inhibiting its activity helps to improve insulin sensitivity. The inhibitory effect of this compound on PTPN1 may improve insulin resistance.
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ABCB1 (P-glycoprotein)
As a drug efflux pump, ABCB1 affects the absorption and distribution of drugs. The interaction between apigenin 7-O-rhamnoside and ABCB1 may affect its bioavailability and pharmacokinetic properties.
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FEN1 (Flipping Enzyme 1)
FEN1 participates in DNA repair and replication, regulating cell proliferation. Its regulation may be related to the anti-tumor potential of the compound.
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PRKCA (protein kinase C alpha)
PRKCA is involved in various signal transduction processes, regulating cellular metabolism and inflammatory responses.
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SIRT1 (silencing information regulatory factor 2 related enzyme 1)
SIRT1 is an important deacetylase that regulates metabolic homeostasis and inflammation. Celericin-7-O-rhamnoside activates SIRT1, which helps delay metabolic aging and inflammation.
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LPAR1 (Lysophosphatidic Acid Receptor 1)
Participate in lipid signaling, regulate adipocyte function and inflammation.
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ENPP2 (Exosomal Nuclease Phosphatase 2)
Affects lipid metabolism and cell migration, and may be involved in adipose tissue remodeling.
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TLR2 (Toll like receptor 2)
Mediate immune inflammatory response and regulate obesity related chronic inflammation.
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FAAH (fatty acid amide hydrolase)
Participate in endogenous cannabinoid metabolism, regulate energy metabolism and appetite.
In summary, apigenin 7-O-rhamnosus gentiopicroside regulates energy metabolism, inflammatory response, and adipocyte function through multi-target synergistic effects, demonstrating its potential in combating obesity and metabolic syndrome.
Evaluation of drug properties and pharmacokinetics
The pharmacological evaluation of apigenin 7-O-rhamnosus gentiopicroside shows that it has good safety and low toxicity. The specific analysis is as follows:
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Molecular weight and polarity
The molecular weight is 732.65 Da, which exceeds the ideal range of traditional oral drugs (<500 Da). The high TPSA value (300 Å ²) and the number of hydrogen bond receptors (19) suggest that its oral absorption may be limited and its bioavailability may be low.
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Fat solubility and membrane permeability
LogP is -3.5, with strong polarity, making it difficult to pass through lipid bilayer membranes. The permeability of the blood-brain barrier is low, limiting its central nervous system function.
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safety
Hepatotoxicity and cardiotoxicity (including hERG channel inhibition) were both negative, and the Ames mutagenicity test showed no mutagenic risk, indicating high safety.
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Pharmacokinetic characteristics
At present, there is a lack of systematic pharmacokinetic data in vivo, but based on its physicochemical properties, it is speculated that its oral absorption is limited, and it may be necessary to optimize its bioavailability through improved formulations or administration routes.
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Metabolic stability
Flavonoid glycosides are usually hydrolyzed and metabolized in gut microbiota and liver. Apigenin 7-O-rhamnoside may release active apigenin through glycoside hydrolysis, exerting pharmacological effects.
Therefore, although the compound itself has certain pharmacokinetic limitations, its safety is excellent, providing a good foundation for further drug development.
Clinical application prospects and prospects
Celericin-7-O-rhamnoside has shown broad application prospects in the fields of anti obesity and metabolic diseases. Future research directions and application prospects include:
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Development of new anti obesity drugs
Combining its multi-target regulatory effects, apigenin 7-O-rhamnoside has the potential to become a natural candidate drug for anti obesity. Improving its pharmacokinetic properties through structural modification or nanocarrier technology can enhance its clinical application potential.
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Regulation of metabolic syndrome syndrome syndrome
This compound not only regulates fat metabolism, but also affects inflammation and insulin signaling pathways, making it suitable for multidimensional treatment of metabolic syndrome.
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Combination therapy strategy
It can be used in combination with other metabolic regulating drugs or natural products to achieve synergistic effects, reduce monotherapy dosage and side effects.
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Preclinical and clinical research
Urgent need for systematic pharmacokinetic, toxicological, and clinical trial data to validate its safety and efficacy, and promote clinical translation.
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Exploring other potential indications
Its anti-inflammatory and antioxidant properties suggest potential for development in fields such as neurodegenerative diseases and cardiovascular diseases.
Conclusion
Celericin-7-O - (2G rhamnose) gentian glycoside, as a natural flavonoid glycoside with unique structure and multiple biological activities, exhibits significant anti obesity and metabolic regulation potential. Its multi-target mechanism of action provides new ideas for the comprehensive treatment of metabolic diseases. Despite certain pharmacokinetic limitations, its good safety and broad pharmacological activity make it a strong candidate for natural product drug development. In the future, through structural optimization, dosage form innovation, and systematic clinical research, it is expected to become a new natural medicine for treating obesity and related metabolic diseases.
