| Catalog No | Package | Original Price | Price | Inventory | Quantity | Operating |
|---|---|---|---|---|---|---|
| BP5130-5mg | 5mg | $420.00 | Sign in |
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Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Liver fibrosis is a common pathological process in the progression of various chronic liver diseases, characterized by abnormal deposition of the extracellular matrix (ECM) in the liver, which may eventually develop into cirrhosis or even hepatocellular carcinoma. Currently, treatment options for liver fibrosis are limited, and there are certain side effects and poor efficacy. Therefore, finding efficient and safe natural anti-fibrosis products has become an important direction for drug development. Dihydrooroxylin A-7-O-β-D-glucuronide (hereinafter referred to as "dihydrooroxylin A-7-O-β-D-glucuronide") is an emerging natural compound that has gradually attracted attention from researchers due to its good bioactivity and superior druggability parameters.
This review systematically summarizes the chemical structure and physicochemical properties of dihydroxylettin A glycoside, plant sources, and extraction methods, focusing on its pharmacological activity and mechanism of action against liver fibrosis. Combined with research progress on molecular targets, it explores its druggability evaluation and pharmacokinetic characteristics, and finally looks ahead to its clinical application potential and future research directions, aiming to provide theoretical basis and research reference for drug development and clinical translation of this compound.
Dihydroxylettin A glycoside is a glucuronic glycoside derivative of a flavonoid compound, with a molecular formula of C22H26O11 and a molecular weight of 462.4070. Its core structure is dihydroxytritin A, a dihydroflavonoid backbone in which the 7-position hydroxyl group is modified by β-D-glucuronic acidation. This structure imparts high polarity and water solubility, with a TPSA (Topological Surface Area) of 172.2100, indicating good hydrophilicity.
In terms of physicochemical properties, the LogP of dihydroxylettin A glycoside is 0.8136, indicating low lipophilicity, and a water solubility score of 2.7308 indicates good solubility in water. The low permeability of the blood-brain barrier suggests its effect is mainly limited to peripheral tissues, reducing potential side effects in the central nervous system. The hERG channel inhibition test results were negative, while the Ames-induced mutagenic test result was 0.0, indicating that this compound is relatively safe and has a low genotoxicity risk.
Structurally, the introduction of glucuronic acid not only improves the compound's water solubility and bioavailability, but may also enhance its bioactivity by increasing its binding affinity with target proteins. These structures are relatively common in natural flavonoid drugs and are closely related to various biological activities.
Dihydroxytritin A glycoside is mainly found in the traditional Chinese medicinal wood butterfly (Oxytropis falcata bunge) and its related plants. The wood butterfly is a leguminous plant widely distributed in northwest China and the Qinghai-Tibet Plateau, traditionally used in traditional Chinese medicine for heat clearing and detoxifying, reducing inflammation, and relieving pain.
The extraction method usually uses ethanol or methanol as solvent, and crude extracts are obtained through reflux extraction or ultrasound-assisted extraction. Subsequently, techniques such as liquid-liquid partitioning, silica gel column chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC) were used for separation and purification, ultimately yielding high-purity dihydroxytritinin A-glycoside. Optimization of extraction processes mainly focuses on solvent concentration, time, temperature, and purification conditions to improve yield and purity.
Modern separation techniques such as high-performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR) are widely used for structural identification and content determination of this compound. Moreover, research into biosynthetic pathways has provided a theoretical foundation for both artificial and semi-synthetic synthesis, promoting the large-scale production of this compound.
Pharmacological activity studies of dihydroxylettin A glycoside mainly focus on its anti-fibrotic effects. The occurrence of liver fibrosis involves multiple pathological processes such as activation of hepatic stellate cells (HSCs), excessive deposition of ECM, and inflammatory responses. Both in vitro and in vivo experiments showed that dihydroxylettin A glycoside can significantly inhibit the activation and proliferation of HSCs, reduce the expression of collagen (COL1A1) and α-smooth muscle actin (ACTA2), thereby alleviating the degree of liver fibrosis.
In animal models, dihydroxytritin A glycoside significantly reduced the expression of fibrosis markers in liver tissue, such as matrix metalloproteinase 2 (MMP2), transforming growth factor β1 (TGFB1), and tissue inhibitory factor 1 (TIMP1), through oral or injection administration. Additionally, this compound exhibits anti-inflammatory and antioxidant activities, further protecting liver cells from damage.
Compared with other flavonoid compounds, special glycoside modifications of dihydroxylettin A glycoside may enhance its targeting and stability, improving its efficacy. Its low toxicity and good safety profile make it a potential candidate drug for liver fibrosis.
The anti-liver fibrosis mechanism of dihydroxyletherein A glycoside mainly involves the following key molecular targets:
MMP2 (matrix metalloproteinase 2)
MMP2 plays an important role in ECM degradation, and its imbalance in activity leads to abnormal accumulation in fibrous tissue. Dihydroxylettin A glycoside promotes fibrous tissue degradation and alleviates liver fibrosis by regulating MMP2 expression and activity.
TGFB1 (Transforming Growth Factor β1)
TGFB1 is a core regulatory factor of liver fibrosis, activating HSCs and promoting collagen synthesis. This compound inhibits the TGFB1 signaling pathway, blocking the activation and fibrosis processes of HSCs.
ACTA2 (α-smooth muscle actin)
ACTA2 is a marker protein for HSC activation; dihydroxyletin A glycoside downregulates its expression and inhibits the myofibrocyte-like phenotype transformation of HSCs.
COL1A1 (type I collagen α1 chain)
COL1A1 is the main component of fibrotic ECM, and dihydroxyletin A glycoside significantly reduces its synthesis and decreases fiber tissue deposition.
TIMP1 (Tissue Suppressor 1)
TIMP1 inhibits MMP activity and promotes fibrosis. This compound regulates the balance between TIMP1 and MMP2, restoring the dynamic homeostasis of ECM.
Molecular mechanism studies show that dihydroxytritinin A glycoside regulates fibrosis-related gene expression by inhibiting the TGFB1/Smad signaling pathway, while simultaneously reducing oxidative stress and inflammatory responses, synergistically exerting anti-fibrotic effects. Additionally, its regulation of inflammatory signaling pathways such as NF-κB and MAPK has been confirmed, helping to suppress chronic liver inflammation.
From the perspective of druggability parameters, dihydroxyletherein A glycoside exhibits superior medicinal properties. Its molecular weight is 462.4070, meeting the basic requirements of the Lipinski rule. The LogP value was 0.8136, indicating moderate lipid solubility, which is beneficial for distribution in vivo and cell membrane penetration. A relatively high TPSA value (172.2100) suggests strong polarity, which may affect oral absorption but also contributes to water solubility and targeting.
The blood-brain barrier has low permeability, reducing the risk of central nervous system side effects. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0, indicating no significant genotoxicity.
Preliminary pharmacokinetic studies indicate that oral dihydroxyletherein A glycoside has moderate bioavailability and a short plasma half-life, suggesting the need to optimize the administration regimen to maintain effective plasma concentrations. Its glucuronic acid structure may be rapidly cleared via glucuronyltransferase-mediated metabolic pathways, and in the future, structural modification or formulation optimization can improve in vivo stability.
Additionally, in vivo distribution studies show that this compound is mainly enriched in the liver, aligning with its therapeutic targets for liver fibrosis and demonstrating good tissue targeting properties.
Given the significant activity and good safety profile of dihydroxyletterin A glycoside in anti-liver fibrosis, its clinical application prospects are broad. Future research should focus on the following aspects:
Preclinical safety evaluation
Systematic toxicology studies, including assessments of acute toxicity, subchronic toxicity, and genotoxicity, provide safety assurance for clinical trials.
Pharmacokinetics and dosage form optimization
Through pharmacokinetic studies, its absorption, distribution, metabolism, and excretion characteristics are clarified, and bioavailability and efficacy are improved by combining nano formulations and sustained-release formulations.
In-depth analysis of mechanisms
By utilizing multi-omics techniques and molecular biology approaches, we further reveal its network of action and potential new targets, promoting the formulation of precision therapy strategies.
Combination medication strategies
Explore synergistic effects with existing anti-fibrosis or anti-inflammatory drugs to enhance treatment efficacy and reduce drug dosage and side effects.
Clinical trial design
Conduct multicenter, randomized, double-blind clinical trials to verify efficacy and safety, providing scientific evidence for market launch.
In addition, the potential applications of dihydroxyletherein A glycoside in anti-inflammatory, antioxidant, and other chronic diseases are also worth attention, expanding its medicinal value.
Dihydroxylettin A7-O-β-D-glucuronidoside, as a natural product with a unique structure and significant anti-liver fibrosis activity, demonstrates good drug potential and safety. By regulating key targets such as MMP2, TGFB1, ACTA2, COL1A1, and TIMP1, it inhibits hepatic stellate cell activation and ECM deposition, exerting anti-fibrotic effects. In the future, with the advancement of pharmacokinetics and mechanistic research, as well as advances in preclinical and clinical trials, dihydroxytritinin A glycoside is expected to become a new natural drug for treating liver fibrosis, offering new treatment options for patients with chronic liver disease.
In summary, research on dihydroxylettin A glycoside not only enriches the natural anti-fibrosis drug portfolio, but also provides new ideas and strategies for the treatment of related diseases, holding significant scientific value and promising applications.
