Product name: Bilobetin
Synonym name:
Catalogue No.: BP0275
Cas No.: 521-32-4
Formula: C₃₁H₂₀O₁₀
Mol Weight: 552.491
Botanical Source: Ginkgo biloba L.
Physical Description:
Type of Compound: Flavonoids

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.

​Description:

Bilobetin treatment ameliorates hyperlipidaemia, lipotoxicity and insulin resistance in rats by stimulating PPARα-mediated lipid catabolism.

References:

Br J Pharmacol. 2012 Apr;165(8):2692-706.    

Bilobetin ameliorates insulin resistance by PKA-mediated phosphorylation of PPARα in rats fed a high-fat diet.   

The amelioration of insulin resistance by Bilobetin is closely related to its hypolipidaemic effect. The aim of the present study was to determine the insulin-sensitizing mechanism of Bilobetin by elucidating its effect on lipid metabolism. 

METHODS AND RESULTS:

Rats fed a high-fat diet were treated with Bilobetin for either 4 or 14 days before applying a hyperinsulinaemic-euglycaemic clamp. Triglyceride and fatty acids labelled with radioactive isotopes were used to track the transportation and the fate of lipids in tissues. The activity of lipid metabolism-related enzymes and β-oxidation rate were measured. Western blot was used to investigate the phosphorylation, translocation and expression of PPARα in several tissues and cultured cells. The location of amino acid residues subjected to phosphorylation in PPARα was also studied.Bilobetin ameliorated insulin resistance, increased the hepatic uptake and oxidation of lipids, reduced very-low-density lipoprotein triglyceride secretion and blood triglyceride levels, enhanced the expression and activity of enzymes involved in β-oxidation and attenuated the accumulation of triglycerides and their metabolites in tissues. Bilobetin also increased the phosphorylation, nuclear translocation and activity of PPARα accompanied by elevated cAMP level and PKA activity. Threonine-129-alanine and/or serine-163-alanine mutations on the PPARα genes and PKA inhibitors prevented the effects of Bilobetin on PPARα. However, cells overexpressing PKA appeared to stimulate the phosphorylation, nuclear translocation and activity of PPARα. 

CONCLUSIONS:

Bilobetin treatment ameliorates hyperlipidaemia, lipotoxicity and insulin resistance in rats by stimulating PPARα-mediated lipid catabolism. PKA activation is crucial for this process. 

HPLC of Bilobetin

HNMR of Bilobetin  

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

Introduction/Overview

7-Demethylated Ginkgo Biflavones (Bilobetin) are an important active biflavonoid in ginkgo leaves. Due to their unique bioactivity and potential medicinal value, they have attracted widespread attention in the field of natural product pharmacology in recent years. Ginkgo biloba, as a traditional Chinese medicinal herb, has been widely studied for its various physiological regulatory effects, with flavonoids being one of its main active ingredients. 7-Demethylated Ginkgo Biflavones not only have a significant lipid-lowering effect, but also improve insulin resistance and regulate lipid metabolism, showing potential therapeutic value for metabolic diseases, especially atherosclerosis. This paper will systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of 7-demethylated ginkgo biflavone, aiming to provide theoretical basis and reference for in-depth research and drug development of this natural product.

Chemical structure and physicochemical properties

The chemical name of 7-desmethylated ginkgo biflavones is Bilobetin, CAS number 521-32-4, and molecular weight 536.48. Its structure belongs to the biflavonoid compounds, featuring a typical flavonoid backbone, containing multiple hydroxyl and methoxy substituents, and ten hydrogen bond receptors in its molecule, which greatly affect its solubility and biological activity. Its LogP value is about 3.0, indicating moderate lipid solubility, which facilitates cell membrane penetration but has relatively low blood-brain barrier permeability. Its topological pole surface area (TPSA) is 189.75 Ų, and the relatively high polar surface area suggests that its uptake and distribution in vivo may be limited by polar environments. 7-Demethylated Ginkgo Biflavones showed no significant hepatotoxicity, cardiotoxicity, or hERG channel inhibition, and the Ames-induced mutagenic test was negative, demonstrating good safety profiles.

Plant Origins and Extraction Methods

7-Demethylated Ginkgo Biflavones are mainly found in ginkgo biloba L. and are one of the important active components in Ginkgo biloba extract (EGb 761). The ginkgo tree belongs to the genus Ginkgo in the ginkgo family, widely distributed in China, Japan, and parts of Europe. Its leaves are rich in flavonoids and terpenes, with diflavonoids accounting for a significant proportion.

Common methods for extracting 7-demethylated ginkgo biflavones include solvent extraction, chromatographic separation, and crystallization purification. Generally, ethanol or methanol is used as extraction solvents, and extraction efficiency is improved through ultrasound-assisted extraction or reflux extraction. Subsequently, silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC) were used for separation and purification, ultimately yielding high-purity 7-desmethylated ginkgo biflavone. In recent years, the application of supercritical CO₂ extraction and membrane separation technologies has also provided new avenues for improving extraction efficiency and purity.

Pharmacological activity research

The pharmacological activity of 7-desmethyl ginkgo diflavones mainly lies in regulating lipid metabolism and improving insulin resistance. Numerous in vivo and in vitro experiments have shown that this compound can reduce plasma triglycerides and very low-density lipoprotein (VLDL) levels, promote hepatic lipid uptake and β-oxidation, decrease lipid accumulation in tissues, and thereby improve metabolic disorders.

In animal models, 7-desmethylated ginkgo biflavones significantly reduced blood triglyceride concentrations, improved insulin sensitivity, and alleviated insulin resistance by enhancing lipid absorption and oxidation in the liver. Its regulatory role in lipid-metabolizing enzymes includes enhancing the expression and activity of fatty acid β-oxidase-related enzymes, inhibiting triglyceride synthesis and secretion, and reducing cellular damage caused by lipid toxicity.

In addition, 7-desmethylated ginkgo biflavones have certain anti-inflammatory and antioxidant effects, which can reduce the inflammatory response and oxidative stress associated with atherosclerosis, protect vascular endothelial function, and slow the progression of arteriosclerosis. It demonstrates good pharmacological potential in improving metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and diabetes-related complications.

Mechanism of action and molecular targets

The mechanism of action of 7-desmethylated ginkgo diflavones involves multiple signaling pathways and molecular targets, mainly achieving pharmacological effects by regulating lipid metabolism and insulin signaling.

First, this compound can significantly promote phosphorylation, nuclear translocation, and transcriptional activity of the peroxisome proliferator-activated receptor α (PPARα). As a key regulator of lipid metabolism, PPARα controls fatty acid uptake, β-oxidation, and triglyceride metabolism. 7-DNGMG diflavones activate PPARα, enhance hepatic lipid metabolism, and lower plasma lipid levels.

Second, 7-DN ginkgo biflavones increase intracellular cAMP levels and protein kinase A (PKA) activity, further promoting PPARα activation and forming a positive regulatory loop. Additionally, this compound activates AMPK (PRKAA1), acting as a sensor for energy metabolism, promoting fatty acid oxidation and glucose metabolism, and improving insulin resistance.

Regarding atherosclerosis-related targets, 7-DNGMG biflavones regulate the expression and function of several key proteins, including:

• LOX-1 (low-density lipoprotein receptor-associated protein 1): Inhibits its mediated uptake of oxidized low-density lipoprotein (oxLDL), reducing vascular endothelial damage.
• ABCA1 (ATP-binding box transporter A1): promotes cholesterol excretion and prevents the formation of atherosclerotic plaques.
• BCL2 and MCL1: regulate apoptosis and protect vascular cell survival.
• EHMT2 (histone methyltransferase): affects inflammation and metabolic gene expression through epigenetic regulation.
• RECQ1: Participates in DNA repair to maintain genome stability.
• IDO1 (Indole Amine 2,3-dioxygenase 1): regulates the immune microenvironment and inhibits inflammatory responses.

In summary, 7-desmethylated ginkgo biflavones regulate lipid metabolism, inflammatory responses, and cell survival through multi-target and multi-pathway synergistic effects, unlocking their potential for the prevention and treatment of metabolic diseases and atherosclerosis.

Druggability evaluation and pharmacokinetics

7-Demethylated Ginkgo Diflavones have good druggability parameters. Its molecular weight of 536.48 meets the applicable range of the Lipinski rule, with a LogP of 3.0, indicating moderate lipid solubility and favorable oral absorption. A higher TPSA (189.75 Ų) may limit its ability to cross the blood-brain barrier, consistent with its weaker role in the central nervous system.

In terms of safety, 7-demethylated ginkgo biflavones showed no hepatotoxicity, cardiotoxicity, or hERG channel inhibition, and the Ames-induced mutagenic test was negative, indicating good safety and low genotoxicity risk.

Pharmacokinetic studies show that oral absorption of this compound is relatively slow, and its bioavailability is limited by its polarity and molecular structure. Its metabolism mainly occurs through liver enzyme systems, with most metabolites being hydroxylated and conjugated compounds. In vivo distribution shows that it is mainly concentrated in the liver and adipose tissue, aligning with its regulatory targets for lipid metabolism.

In the future, optimizing its pharmacokinetic performance through structural modification and drug carrier technology is expected to enhance its clinical application value.

Prospects and outlooks for clinical applications

Given the significant effects of 7-demethylated ginkgo biflavones in regulating lipid metabolism, improving insulin resistance, and anti-atherosclerosis, they have broad clinical application prospects in metabolic syndrome, type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular diseases.

Currently, although there is a large amount of in vivo and in vitro experimental data supporting its pharmacological activity, clinical studies remain relatively lacking. In the future, preclinical safety evaluation and pharmacokinetic studies should be strengthened, with multicenter, randomized controlled clinical trials conducted to verify efficacy and safety.

Moreover, combining modern drug formulation technologies, such as nanocarriers and sustained-release formulations, is expected to improve bioavailability and targeting, enhancing therapeutic outcomes. By combining them with other drugs, they can exert synergistic effects and expand their clinical indications.

At the same time, in-depth analysis of its molecular mechanisms and multi-target networks helps discover new therapeutic targets and disease associations, providing fresh ideas for the development of natural product drugs.

Conclusion

7-Demethylated Ginkgo Biflavones, as an important biflavonoid active ingredient in ginkgo leaves, demonstrates promising drug development potential due to its multiple pharmacological effects such as regulating lipid metabolism, improving insulin resistance, and anti-atherosclerosis. Its multi-target and multi-pathway mechanism of action offers new strategies for the treatment of metabolic and cardiovascular diseases. In the future, through systematic pharmacological research, pharmacokinetic optimization, and clinical validation, it is expected that 7-demethylated ginkgo biflavones will be developed into safe and effective natural medicines, contributing to the prevention and treatment of related diseases.