Product name: Ginkgolide A
Synonym name:
Catalogue No.: BP0646
Cas No.: 15291-75-5
Formula: C₂₀H₂₄O₉
Mol Weight: 408.403
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.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

Description:

Ginkgolide A is a platelet-activating factor antagonist, it can inhibit the neurotoxicity of prions or amyloid-beta1-42, may be relevant treatments for prion or Alzheimer's diseases.Ginkgolide A has neuroprotective, and anxiolytic-like effects, it is widely used for the treatment of cardiovascular diseases and diabetic vascular complications, which might be achieved through regulating the STAT3-mediated pathway.

References:

Int Immunopharmacol. 2015 Apr;25(2):242-8.    

Ginkgolide A reduces inflammatory response in high-glucose-stimulated human umbilical vein endothelial cells through STAT3-mediated pathway.    

High-glucose-induced low-grade inflammation has been regarded as a key event in the onset and progression of endothelial dysfunction in diabetic vascular complications. Ginkgolide A (GA), a major compound from Ginkgo biloba extract, is widely used for the treatment of cardiovascular diseases and diabetic vascular complications. Here, its effect on high-glucose-stimulated vascular inflammation in human umbilical vein endothelial cells (HUVECs) was investigated. 

METHODS AND RESULTS:

In the present study, the optimal stimulation conditions for HUVECs were screened for inducing endothelial inflammation, namely, high glucose at the concentration of 30mM for continuous 8h. The endothelial production of high-glucose-induced interleukin (IL)-4, IL-6, IL-13 and signal transducer and activator of transcription-3 (STAT-3) phosphorylation were significantly inhibited by the pretreatment with GA at concentrations of 10, 15 and 20μM based on enzyme-linked immunosorbent assay (ELISA), western blot or/and RT-PCR experiments. These senescent alterations induced by high glucose were significantly attenuated by the specific STAT3 inhibitor S3I-201 at the concentration of 20μM. Furthermore, the phosphorylation of STAT3, IL-4, IL-6, IL-13 and intercellular cell adhesion molecule-1 (ICAM-1) protein as well as mRNA levels were attenuated by the pretreatment of cells with STAT3 siRNA. Our results demonstrated that GA improved high-glucose-caused low-grade vascular inflammation, which might be achieved through regulating the STAT3-mediated pathway. 

CONCLUSIONS:

These findings indicated that GA might be a promising candidate for attenuating vascular inflammation in diabetic vascular complications.    

J Nat Prod. 2003 Oct;66(10):1333-7.    

An anxiolytic-like effect of Ginkgo biloba extract and its constituent, ginkgolide-A, in mice.    

The anxiolytic-like effects of Ginkgo biloba extract (GBE) and its four terpenoid components (Ginkgolide A, ginkgolide B, ginkgolide C, and bilobalide) were assessed using the elevated plus-maze test in mice. 

METHODS AND RESULTS:

Administration of GBE as a single oral dose (0.5 or 1 g/kg, po) caused a state of suppressed motor activity and, thus, shortened the time spent in the open-sided arms. However, when GBE (0.063-1 g/kg, po) was administered daily for 7 days and the plus-maze test was carried out 24 h after the final administration, the time spent in the open-sided arms was prolonged, with the peak anxiolytic-like effect at 0.125 g/kg. A combination of seven-day administration of GBE (0.125 g/kg) and a single dose of diazepam (1 mg/ kg, po, 10 min before testing) enhanced the anxiolytic-like effect. Flumazenil (0.3 mg/kg, ip, 10 min before testing) blocked the effect of diazepam, but not of GBE. Daily administration of Ginkgolide A (1 or 2 mg/kg, po) resulted in an anxiolytic-like effect by the third treatment, with the maximal effect observed after the fifth administration. Neither ginkgolide B, ginkgolide C, nor bilobalide produced any anxiolytic-like effects. At doses higher than 0.5 g/kg, GBE not only inhibited motor activity but also suppressed active avoidance behavior, reduced caffeine-induced stimulation, and enhanced pentobarbital-induced sleep, while Ginkgolide A (up to 20 mg/kg) did not exhibit these effects. Diazepam (1 mg/kg) is known to enhance pentobarbital-induced sleep. 

CONCLUSIONS:

These results suggest that GBE produces a significant anxiolytic-like effect following repeated administration and that Ginkgolide A is most likely responsible for this effect. There are also indications that although GBE exerts a sedative effect at comparatively higher doses, Ginkgolide A has a relatively weak tendency to produce benzodiazepine-like side effects.    

HPLC of Ginkgolide A

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

Introduction/Overview

Ginkgolide A (CAS number: 15291-75-5), as one of the important terpenoid lactones in Ginkgo biloba leaves, has received widespread attention since its isolation and identification in the late 20th century due to its unique chemical structure and diverse biological activities, especially its potential in the field of neuroprotection. Ginkgo biloba leaf extract has been widely used in traditional medicine for a long time. Modern pharmacological studies have revealed that its main active ingredients, ginkgolides, have multiple pharmacological effects such as anti platelet aggregation, anti-inflammatory, antioxidant, and neuroprotective properties. Ginkgolide A, as a natural GABA receptor antagonist, has shown the ability to regulate neurotransmitter function and protect nerve cells from damage, making it a hot molecule in the study of neurodegenerative diseases and related neurological pathological states.

This article aims to systematically review the chemical structure and physicochemical properties, plant sources, and extraction methods of ginkgolide A, explore its pharmacological activity and mechanism of action, focus on analyzing its molecular targets related to neuroprotection, evaluate its pharmacological and pharmacokinetic characteristics, and look forward to its potential and challenges in clinical applications. By integrating the latest research progress, provide theoretical basis and research direction for the drug development and clinical translation of ginkgolide A.

Chemical structure and physicochemical properties

Ginkgolide A has a molecular formula of C20H24O9 and a molecular weight of 408.4030, belonging to the sesquiterpene lactone class. Its structural feature is a unique triterpenoid skeleton containing multiple lactone rings and hydroxyl groups, endowing it with strong biological activity. There are multiple oxidative functional groups in the chemical structure, including lactone rings and alcohol hydroxyl groups, which have important effects on the hydrophilicity of molecules and their binding to biological targets.

In terms of physicochemical properties, the LogP value of ginkgolide A is 0.7444, indicating its moderate lipid solubility, which is beneficial for penetrating cell membranes and the blood-brain barrier. Its topological polar surface area (TPSA) is 128.59 Å ², indicating high polarity characteristics that may affect its oral absorption and bioavailability. The water solubility is 0.1950 mg/mL, which belongs to low solubility compounds, indicating the need to consider solubility enhancement strategies in formulation development. Importantly, ginkgolide A has a high blood-brain barrier permeability, which lays the foundation for its neurological function. In addition, the hERG channel inhibition experiment showed a negative result, indicating a low risk of cardiac toxicity; The Ames mutagenicity test score is 0.9, indicating a low risk of genotoxicity and good safety potential.

Plant sources and extraction methods

Ginkgolide A mainly comes from the leaves of Ginkgo biloba L., which is a living fossil plant rich in various bioactive components. The content of ginkgolides in Ginkgo biloba leaves is relatively low, usually accounting for a small portion of the total terpenoid lactones, but their biological activity is significant.

The extraction of ginkgolide A is usually carried out using organic solvent extraction combined with chromatographic separation and purification techniques. Common extraction solvents include ethanol, methanol, and their aqueous solutions to ensure the dissolution of active ingredients. The extraction process generally includes the following steps:

1. Drying and crushing After drying, ginkgo leaves are crushed into fine powder to increase the solvent contact area.
2. Solvent extraction Multiple extractions were carried out using 70% ethanol or methanol aqueous solution to extract ginkgolides and other active ingredients.
3. Crude extract concentration Reduce pressure and concentrate to remove the solvent, obtaining a concentrated extract.
4. Separation and purification Separation and purification of ginkgolide A were achieved through methods such as silica gel column chromatography and high-performance liquid chromatography (HPLC). Reverse phase HPLC combined with mass spectrometry detection is currently a commonly used qualitative and quantitative method.

In recent years, green and efficient technologies such as ultrasound assisted extraction and microwave-assisted extraction have gradually been applied to the extraction of ginkgolide A, significantly improving extraction efficiency and reducing solvent usage. In addition, molecular imprinting technology and membrane separation technology have also been explored for high-purity separation of ginkgolides.

Pharmacological activity research

The pharmacological activity of ginkgolide A mainly focuses on neuroprotective effects, and also exhibits anti-inflammatory, antioxidant, and neurotransmitter regulating functions. Its properties as a GABA receptor antagonist make it potentially valuable in regulating neural excitability and improving cognitive function.

Neuroprotective effect

Numerous in vitro and in vivo studies have shown that ginkgolide A can exert neuroprotective effects through multiple signaling pathways. Its main manifestations are:

• anti-oxidative stress Ginkgolide A can activate the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, enhance cellular antioxidant enzyme activity, reduce reactive oxygen species (ROS) generation, and alleviate oxidative damage.
• Inhibit neuroinflammation By regulating MAPK1 (mitogen activated protein kinase) signaling, inhibiting the release of pro-inflammatory factors, and reducing neuroinflammatory responses.
• anti-apoptotic Ginkgolide A upregulates BCL2 (anti apoptotic protein) expression, inhibits CASP3 (caspase 3) activation, and reduces neuronal apoptosis rate.
• Regulating neurotransmitters As a GABA receptor antagonist, ginkgolide A regulates gamma aminobutyric acid (GABA) - mediated neural inhibitory signals, promotes neural excitability balance, and helps improve cognitive impairment and memory function.

Other pharmacological effects

• Antiplatelet aggregation Ginkgolide A inhibits platelet activating factor (PAF) receptors, reduces platelet aggregation, and has potential antithrombotic effects.
• Improve cerebral blood flow By dilating cerebral blood vessels, improving cerebral microcirculation, and assisting in neuroprotection.
• Anti neurodegenerative diseases Ginkgolide A has shown potential in regulating the metabolism of amyloid precursor proteins and abnormal phosphorylation of tau protein, targeting Alzheimer's disease (AD) related targets APP, BACE1, and MAPT.

Mechanism of action and molecular targets

The neuroprotective effect of ginkgolide A involves multi-target and multi pathway synergistic regulation. The main targets and their mechanisms of action are as follows:

• BCL2 and CASP3 Ginkgolide A upregulates BCL2 expression, inhibits CASP3 activation, blocks the apoptotic signaling pathway, and protects neuronal survival.
• APP and BACE1 Regulating the metabolism of amyloid precursor protein (APP), inhibiting the activity of β - secretase 1 (BACE1), reducing the production of β - amyloid protein (A β), and slowing down the pathological process of Alzheimer's disease.
• MAPT Affects abnormal phosphorylation of tau protein (MAPT), prevents the formation of neurofibrillary tangles, and maintains microtubule stability.
• SIRT1 Activate the deacetylase SIRT1, regulate cellular metabolism and antioxidant response, and delay neuronal aging.
• MAPK1 Regulating mitogen activated protein kinase signaling, inhibiting the expression of inflammatory factors, and reducing neuroinflammation.
• ACHE Regulating acetylcholinesterase activity, maintaining cholinergic nerve function, and improving cognitive impairment.
• SNCA: Affects the aggregation of alpha synuclein (SNCA) and prevents Parkinson's disease-related neurotoxicity.
• NRF2 Activate the NRF2 signaling pathway, induce the expression of antioxidant enzymes, and enhance cellular antioxidant capacity.

Ginkgolide A exerts a comprehensive neuroprotective effect through the synergistic action of multiple targets mentioned above, demonstrating its advantages as a multi-target drug.

Evaluation of drug properties and pharmacokinetics

The pharmacological evaluation of ginkgolide A shows that it has good potential for drug development:

• Molecular weight and lipid solubility The molecular weight is 408.4, with a LogP of approximately 0.74, which is within the ideal range of the drug and beneficial for oral absorption and blood-brain barrier penetration.
• Polarity and solubility TPSA 128.59 is relatively high and has low water solubility, indicating that oral bioavailability may be limited. It is necessary to optimize the formulation or use nanocarriers and other technologies to improve dissolution.
• safety HERG channel inhibition is negative, reducing the risk of cardiac toxicity; The Ames test score is 0.9, indicating a low risk of genotoxicity.
• Blood-brain barrier permeability High blood-brain barrier permeability is the basis of its neuroprotective effect, ensuring that drugs effectively reach the central nervous system.
• pharmacokinetics At present, there is relatively little research on the in vivo metabolism and excretion of ginkgolide A. Preliminary data indicate that it is widely distributed in the body, mainly metabolized through the liver enzyme system, with a moderate half-life and suitable for clinical application.

In the future, further systematic research is needed on its pharmacokinetic parameters, including absorption, distribution, metabolism, excretion (ADME) characteristics and potential drug interactions, to provide a basis for clinical dose design.

Clinical application prospects and prospects

Ginkgolide A has shown broad application prospects in the treatment of neurodegenerative diseases, cerebrovascular diseases, and cognitive impairments due to its significant neuroprotective effects. Especially in disease models such as Alzheimer's disease, Parkinson's disease, and ischemic brain injury, ginkgolide A regulates neuropathological processes through multiple targets, improves neurological function, and has potential disease modifying effects.

Preclinical studies support that ginkgolide A, as an active ingredient in monomeric drugs or Ginkgo biloba leaf extracts, has the potential to be developed as a therapeutic drug for neurological diseases. Combining modern drug delivery technologies such as nanocarriers, liposomes, etc., it is expected to overcome their solubility limitations, enhance bioavailability and targeting.

Future research directions include:

• In depth mechanism research Further elucidate the molecular mechanism and signaling network of ginkgolide A in neuroprotection.
• Pharmacokinetic and Toxicological Evaluation Improve metabolic pathways and long-term safety data in the body.
• Clinical trial design Conduct randomized controlled clinical trials for patients with neurodegenerative diseases to verify their efficacy and safety.
• Structural optimization and derivative development Design more efficient and selective derivative compounds based on the ginkgolide A skeleton.

In summary, ginkgolide A, as a multi-target neuroprotective natural product, has great potential as a drug and is expected to become an important candidate for the treatment of neurological diseases in the future.

Conclusion

Ginkgolide A, as an important active ingredient in Ginkgo biloba leaves, has become a focus of natural product pharmacology research due to its unique chemical structure and multi-target neuroprotective effects. Its comprehensive effects in antioxidant, anti-inflammatory, anti apoptotic, and neurotransmitter regulation provide new ideas and strategies for the treatment of neurodegenerative diseases. Although there are still certain challenges in pharmacokinetics and clinical applications, with the continuous progress of extraction technology, drug delivery systems, and molecular mechanism research, the drug development prospects of ginkgolide A are broad. In the future, through interdisciplinary collaborative research, it is expected to promote the transition of ginkgolide A from laboratory to clinical use, benefiting a large number of patients with neurological diseases.