Product name: Ginkgolide C
Synonym name:
Catalogue No.: BP0648
Cas No.: 15291-76-6
Formula: C₂₀H₂₄O₁₁
Mol Weight: 440.401
Botanical Source: Ginkgo biloba L.
Physical Description:
Type of Compound: Diterpenoids

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:

Ginkgolide C is a potent inhibitor of collagen-stimulated platelet aggregation, it may increase intracellular cAMP and cGMP production and MMP-9 activity, inhibit intracellular Ca(2+) mobilization and TXA(2) production. Ginkgolide C has anti-adipogenic and ameliorating Alzheimer disease effects; it also can increase△LVP significantly,enhances the myocardial systolic and diastolic function of rats,but has no significant effect on HR while it shows inotropic activity.

References:

Evid Based Complement Alternat Med. 2015; 2015: 298635.    

Ginkgolide C Suppresses Adipogenesis in 3T3-L1 Adipocytes via the AMPK Signaling Pathway   

Ginkgolide C, isolated from Ginkgo biloba leaves, is a flavone reported to have multiple biological functions, from decreased platelet aggregation to ameliorating Alzheimer disease. The study aim was to evaluate the antiadipogenic effect of Ginkgolide C in 3T3-L1 adipocytes.

METHODS AND RESULTS:

Ginkgolide C was used to treat differentiated 3T3-L1 cells. Cell supernatant was collected to assay glycerol release, and cells were lysed to measure protein and gene expression related to adipogenesis and lipolysis by western blot and real-time PCR, respectively. Ginkgolide C significantly suppressed lipid accumulation in differentiated adipocytes. It also decreased adipogenesis-related transcription factor expression, including peroxisome proliferator-activated receptor and CCAAT/enhancer-binding protein. Furthermore, Ginkgolide C enhanced adipose triglyceride lipase and hormone-sensitive lipase production for lipolysis and increased phosphorylation of AMP-activated protein kinase (AMPK), resulting in decreased activity of acetyl-CoA carboxylase for fatty acid synthesis. In coculture with an AMPK inhibitor (compound C), Ginkgolide C also improved activation of sirtuin 1 and phosphorylation of AMPK in differentiated 3T3-L1 cells. 

CONCLUSIONS:

The results suggest that Ginkgolide C is an effective flavone for increasing lipolysis and inhibiting adipogenesis in adipocytes through the activated AMPK pathway.    

Proceeding of Clinical Medicine, 2013, 22(7):524-6.    

Effect of Ginkgolide C in cardiac function of rats in the body.    

To study the effect of Ginkgolide C(GC) in cardiac function of rats in the body.

METHODS AND RESULTS:

: Normal rats after anesthetized,inserted the intubate which connecting the pressure transducer into left ventricular from the right common carotid artery,then detected the cardiac function by the PowerLab biological signal acquisition system.Gave each of saline,1‰dimethyl sulfoxide(DMSO),100 μ mol / L GC,1 000 μ mol / L GC 1ml from the jugular vein,detected the cardiac function before and after administration by continuous recording the left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),the maximal rate of pressure increase in systole phase(+dp / dtmax),maximal rate of pressure decrease in diastole phase(-dp / dtmax) and heart rate(HR).Compared with normal conditions,when given 100 μ mol / L GC,there are no significant effect on cardiac function;when given 1 000 μ mol / L GC,it showed inotropic activity by increasing △LVP,+dp / dtmax,-dp / dtmax significantly,but had no significant effect on HR. 

CONCLUSIONS:

Ginkgolide C can increase△LVP significantly,enhances the myocardial systolic and diastolic function of rats,but has no significant effect on HR while it shows inotropic activity.    

HPLC of Ginkgolide C

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

Introduction/Overview

Ginkgolide C (CAS No.: 15291-76-6) is an important class of flavonoid natural products isolated from ginkgo leaves and is a member of the ginkgo lactone family. Ginkgo biloba, an ancient gymnosperm, has long attracted widespread attention in both traditional medicine and modern drug development due to its leaf extracts rich in bioactive components and diverse pharmacological effects. Ginkgo lactone C, with its unique chemical structure and multi-target bioactivity, shows significant potential especially in neuroprotection, anti-platelet aggregation, and cognitive function improvement, making it a hot topic in natural product pharmacology research.

In recent years, with the continuous rise in the incidence of neurodegenerative diseases such as Alzheimer's disease (AD), the demand for developing natural products for neuroprotective drugs has been steadily increasing. Ginkgo lactone C demonstrates the advantage of multi-target synergy by regulating multiple neuroprotection-related signaling pathways, making it an important candidate for exploring novel neuroprotective agents. This paper will systematically review the chemical structure and physicochemical properties of ginkgo lactone C, plant origin and extraction methods, pharmacological activity and mechanism, druggability evaluation and pharmacokinetic characteristics, and, combined with its potential value in clinical applications, comprehensively analyze the research progress and future directions of this natural product.

Chemical structure and physicochemical properties

Ginkgo lactone C has a chemical formula of C20H24O9 and a molecular weight of 440.4010 Da. Its structural feature is a polycyclic lactone backbone, containing multiple hydroxyl groups and ether rings, and it belongs to the flavonoid lactone compounds. The abundance of oxygen functional groups in the molecule gives it high polarity, reflected in its high topological pole surface area (TPSA) of 169.05 Ų, indicating the molecule's good hydration capacity.

In terms of physicochemical properties, the LogP value of ginkgo lactone C is -0.2528, indicating strong hydrophilicity and water solubility of 1.1149, supporting good solubility in the aqueous phase. Its low blood-brain barrier (BBB) permeability suggests limited ability to cross BBB, which poses challenges for neurological drug design but may also reduce central nervous system side effects. The hERG channel inhibition test results were negative, indicating that ginkgo lactone C has a lower risk of cardiotoxicity. The Ames mutagenicity test scored 0.9, indicating a low genotoxicity risk and a solid safety foundation.

Ginkgo lactone C has a complex chemical structure, containing multiple chiral centers, which imparts its stereochemical diversity, which significantly affects its bioactivity and target binding specificity. Its lactone ring structure is a key structural group for its bioactivity, and related studies have shown that this structure is crucial for its anti-platelet aggregation and neuroprotective effects.

Plant Origins and Extraction Methods

Ginkgo lactone C is mainly extracted from ginkgo biloba L. Ginkgo leaves contain various active ingredients, with ginkgo lactone compounds being one of their main secondary metabolites. Ginkgo leaves are usually harvested during autumn when the leaves mature to ensure the highest levels of lactone compounds.

The extraction process typically uses organic solvent extraction combined with separation and purification technology. Traditional methods include ethanol or methanol extraction, followed by coarse separation and purification through liquid-liquid separation and column chromatography (such as silica gel columns and reversed-phase C18 columns). In recent years, green and efficient technologies such as ultrasound-assisted extraction, microwave-assisted extraction, and supercritical CO2 extraction have been introduced, improving extraction efficiency and purity.

During purification, high-performance liquid chromatography (HPLC) and preparative chromatography techniques were used to separate and identify ginkgo lactone C, and its structure was confirmed using methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR). Optimizing the extraction and purification processes of ginkgo lactone C is of great significance for obtaining high-purity samples and for subsequent pharmacological research.

Pharmacological activity research

Ginkgo lactone C exhibits a variety of important pharmacological activities, mainly including anti-platelet aggregation, neuroprotection, anti-inflammatory, and antioxidant effects.

Anti-platelet aggregation effect

Ginkgo lactone C can effectively inhibit platelet aggregation and reduce the risk of thrombosis. Its mechanism involves inhibiting the release of calcium ions within platelets and suppressing the signaling of platelet activation factors. This action has potential value in preventing cardiovascular and cerebrovascular diseases such as cerebral infarction and myocardial infarction.

Neuroprotective effects

Ginkololactone C has been particularly studied in neurological diseases, particularly for its improvement effect on Alzheimer's disease. Through multi-target regulation, it slows neuron apoptosis, inhibits β-amyloid protein (Aβ) deposition, and improves cognitive dysfunction. Animal model studies show that ginkgo lactone C can reduce neuroinflammation, inhibit oxidative stress, promote nerve regeneration, and significantly improve cognitive abilities.

Anti-inflammatory and antioxidant effects

Ginkgo lactone C activates the nuclear factor red-related factor 2 (NRF2) signaling pathway, enhances cellular antioxidant defense systems, reduces reactive oxygen species (ROS) levels, and alleviates oxidative damage. At the same time, it inhibits the release of pro-inflammatory factors, reduces inflammatory responses, and has potential therapeutic effects for various chronic inflammatory diseases.

Mechanism of action and molecular targets

The multi-target mechanism of ginkolide C is the basis for its pharmacological activity. Its main targets involve key proteins and signaling pathways related to neuroprotection:

• BCL2: Ginkgo lactone C upregulates the expression of the anti-apoptotic protein BCL2, inhibiting neuronal apoptosis and maintaining cell survival.
• APP and BACE1: Regulates amyloid precursor protein (APP) metabolism, inhibits β-secretase (BACE1) activity, reduces Aβ production, and alleviates the pathological features of Alzheimer's disease.
• MAP (Tau protein): Regulates abnormal phosphorylation of tau protein, prevents nerve fiber tangling formation, and protects neuronal structural integrity.
• SIRT1: Activates the deacetylase SIRT1, regulates cellular energy metabolism and antioxidant responses, and slows the progression of neurodegeneration.
• MAPK1: Regulates the mitogen-activated protein kinase (MAPK) signaling pathway, involved in cellular stress responses and inflammation regulation.
• ACHE: Inhibits acetylcholinesterase (ACHE) activity, prolongs the duration of acetylcholine's action, and improves cognitive function.
• CASP3: Inhibits caspase-3 (CASP3)-mediated apoptosis, protecting nerve cells.
• SNCA: Regulates α-synuclein (SNCA) expression to prevent neurotoxicity related to Parkinson's disease.
• NRF2: Activates the NRF2 antioxidant signaling pathway, enhancing cellular antioxidant capacity and reducing oxidative stress damage.

Ginkgo lactone C forms a comprehensive neuroprotective network by co-regulating these multi-target sites, demonstrating its therapeutic potential in complex neuropathological environments.

Druggability evaluation and pharmacokinetics

The druggability evaluation of ginkgo lactone C shows it has certain development potential, but there are also challenges. The molecular weight of 440.4 Da falls within the suitable molecular range for the drug, but higher TPSA and negative LogP suggest strong hydrophilicity, which may limit oral absorption and cell membrane permeability. The low permeability of the blood-brain barrier limits its ability to act directly on the central nervous system, suggesting the need to optimize drug delivery systems or structural modifications to increase brain concentrations.

In terms of safety, the hERG channel inhibition test was negative, reducing the risk of cardiotoxicity. Ames trial results also show a lower risk of genotoxicity, providing safety assurance for clinical applications.

Pharmacokinetic studies show that ginkgo lactone C is metabolized stably in the body, mainly through hepatic enzyme systems, with excretion primarily via the kidneys. Its bioavailability is limited, and further research is needed on dosage form improvement strategies, such as nanocarriers and liposome encapsulation, to enhance its pharmacokinetic properties.

Prospects and outlooks for clinical applications

Ginkgo lactone C, with its multi-target neuroprotective effects and anti-platelet aggregation activity, has broad clinical application prospects in neurodegenerative diseases, cardiovascular and cerebrovascular diseases, and other fields. Especially in adjunctive treatment for Alzheimer's disease, ginkgo lactone C can improve cognitive function and slow disease progression, demonstrating the unique advantages of natural drug products.

Future research should focus on:

1. Structural optimization and derivative development: Chemical modification enhances the penetration and bioavailability of the blood-brain barrier, enhancing neuroprotective effects.
2. Drug delivery system innovation: Developing nanocarriers targeting the central nervous system to increase the concentration and therapeutic effect of ginkgo lactone C in the brain.
3. Clinical trial validation: Conduct systematic clinical studies to evaluate the safety and efficacy of ginkgo lactone C in neurodegenerative and vascular diseases.
4. In-depth analysis of multi-target mechanisms: Using modern molecular biology techniques, its complex network of actions is further revealed, providing a theoretical foundation for precision treatment.

In summary, ginkgo lactone C, as a naturally occurring product with significant biological activity, is expected to become an important candidate drug for neuroprotection and the treatment of cardiovascular and cerebrovascular diseases in the future.

Conclusion

Ginkgo lactone C, an important flavonoid lactone compound in ginkgo leaves, demonstrates broad application potential in anti-platelet aggregation and neuroprotection due to its unique chemical structure and multi-target pharmacological activity. By regulating key targets such as BCL2, APP, BACE1, MAPT, SIRT1, MAPK1, ACHE, CASP3, SNCA, and NRF2, it exerts comprehensive neuroprotective and anti-inflammatory antioxidant effects, providing new approaches for the treatment of neurodegenerative diseases like Alzheimer's.

Although ginkgo lactone C has certain limitations in druggability, its low toxicity and good safety provide a foundation for clinical development. In the future, through structural optimization and innovations in drug delivery technology, existing obstacles are expected to be overcome, promoting the translation of ginkgo lactone C into clinical applications.

Overall, as a model for pharmacological research of natural products, ginkgo lactone C demonstrates the unique advantages and broad prospects of natural compounds in multi-target disease treatment, and is worthy of further exploration and development.