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Name: Ginkgolide K
Synonym name:
Catalogue No.: BP4017
Cas No.: 153355-70-5
Formula: C20H22O9
Mol Weight: 406.39
Botanical Source: Ginkgo biloba (ginkgo)
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
HPLC of Ginkgolide K
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
128.5900
.9760
.9759
.3276
1.5355
6.1330
High
34.4701
6.1315
Yes
No
No
No
Yes
No
0.9
Yes
No
Yes
Yes
Ginkgolide K (CAS No. 153355-70-5) was used as Ginkgo biloba) has recently attracted widespread attention due to its significant neuroprotective effects and unique molecular mechanisms. Ginkgo lactone K belongs to the ginkgo lactone class of compounds with a complex sesquiterpene lactone framework structure, capable of regulating multiple cellular signaling pathways, and especially demonstrates potential application value in the prevention and treatment of neurological diseases. In pathological processes of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and ischemic brain injury, pathological mechanisms including oxidative stress, neuroinflammation, and autophagy dysfunction intertwine. Ginkgo lactone K induces protective autophagy by modulating the AMPK/mTOR/ULK1 signaling pathway, thereby exerting neuroprotective effects and becoming a hot topic in natural drug research.
This paper aims to systematically review the chemical structure and physicochemical properties of ginkgo lactone K, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, as well as its clinical application prospects and future research directions, providing comprehensive reference materials for researchers in the field of natural product pharmacology.
Ginkgo lactone K is a sesquiterpene lactone compound with a molecular formula of C20H22O9 and a molecular weight of 406.3870. Its structural features include a polycyclic lactone backbone containing multiple hydroxyl and lactone groups, which imparts good bioactivity and a certain degree of hydrophilicity. The LogP value is 0.9760, indicating moderate lipid solubility, which facilitates cell membrane penetration. The topological pole surface area (TPSA) is 128.59 Ų, indicating high polarity and favorable for binding with biological macromolecules. Water solubility is 0.3276, making it a moderately water-soluble compound.
It is worth noting that ginkgo lactone K has a high blood-brain barrier penetration ability, which is especially important for neurological drugs. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. Ames mutagenic assay score was 0.9, indicating a low genotoxicity risk and meeting safety requirements.
The chemical structure of ginkgo lactone K is shown in the figure below (the diagram is omitted here). Its polyhydroxyl group and lactone ring structure provide the basis for its biological activity and also enable its synthetic modification.
Ginkgo lactone K is mainly isolated from ginkgo leaves and seeds. As a "living fossil" plant, ginkgo contains abundant ginkgo lactone compounds, especially ginkgo lactones A, B, C, and ginkgo lactone K. Traditional extraction methods include solvent extraction, ultrasound-assisted extraction, and supercritical fluid extraction.
The typical extraction process is: first, the dried ginkgo leaves are crushed, then extracted using ethanol or methanol as solvents. The extract is concentrated and purified by silica gel column chromatography, reversed-phase high-performance liquid chromatography (RP-HPLC), and other methods, ultimately obtaining high-purity ginkgo lactone K. In recent years, the application of ultrasound-assisted extraction and supercritical CO2 extraction technologies has improved extraction efficiency and purity, making them more environmentally friendly.
The content of ginkgo lactone K is greatly affected by the plant growth environment, harvest season, and extraction process. Optimizing extraction conditions is crucial for obtaining high-purity, highly active ginkgo lactone K.
The pharmacological activity of ginkgo lactone K is mainly concentrated in the neuroprotective field, showing a comprehensive effect of multiple targets and multiple mechanisms.
Ginkolide K can significantly reduce oxidative stress damage to nerve cells, inhibit neuroinflammatory responses, and promote neuron survival. Both in vitro cell models and in vivo animal models have confirmed its protective effects against ischemic brain injury and neurodegenerative diseases. For example, in the ischemia-reperfusion injury model, ginkgo lactone K activates the AMPK signaling pathway, inhibits mTOR, induces ULK1-mediated autophagy, promotes clearance and repair of damaged cells, and significantly improves neural function.
Ginkgo lactone K can activate the nuclear factor 2-associated factor 2 (NRF2) pathway, enhance intracellular antioxidant enzyme expression, reduce reactive oxygen species (ROS) levels, and alleviate oxidative damage. At the same time, it inhibits the expression of inflammatory mediators such as TNF-α and IL-1β, reducing neuroinflammation and protecting nerve tissue.
Ginkgo lactone K also improves neurotransmitter metabolism and promotes nerve signal transduction by regulating acetylcholinesterase (ACHE) activity. Additionally, it regulates apoptosis-related proteins such as BCL2 and CASP3, inhibits neuronal apoptosis, and maintains the stability of neural networks.
Ginkgo lactone K can regulate the expression of Alzheimer's disease-related protein APP and its enzyme BACE1, reduce β-amyloid (Aβ) deposition, and slow neurodegenerative changes. It also regulates microtubule-associated protein tau (MAPT) and α-synuclein (SNCA), potentially intervening in the pathological progression of Parkinson's disease and other diseases.
The neuroprotective effects of ginkgo lactone K involve multiple signaling pathways and molecular targets, reflecting its multi-target pharmacological properties.
Ginkgo lactone K inhibits mammalian rapamycin target protein complex 1 (mTORC1) by activating 5' AMP-activated protein kinase (AMPK), promoting activation of the autophagy-related protein ULK1, and inducing protective autophagy. Autophagy, as a key mechanism for clearing damaged proteins and organelles within cells, helps maintain neuronal homeostasis and alleviates ischemia and toxic damage.
Ginkolide K activates the NRF2 signaling pathway, promoting the expression of antioxidant enzymes such as glutathione peroxidase (GPx) and superoxide dismutase (SOD), clearing excess ROS and protecting nerve cells from oxidative damage.
By regulating nuclear factor κB (NF-κB) and related inflammatory factors, ginkgo lactone K suppresses neuroinflammatory responses. At the same time, it regulates the activities of BCL2 family proteins and CASP3, blocks the cell apoptosis signaling pathway, and promotes neuron survival.
Ginkgo lactone K downregulates the expression of β-amyloid precursor protein (APP) and β-secretase (BACE1), reducing Aβ production and deposition, and slowing the pathological progression of Alzheimer's disease. Regulation of tau protein (MAPT) and α-synuclein (SNCA) helps inhibit nerve fiber tangles and Lewy body formation, reducing neuronal damage.
Ginkolide K also affects signaling molecules such as SIRT1 and MAPK1, regulating cellular metabolism, inflammation, and stress responses, further enhancing its neuroprotective effects.
Ginkolide potassium has excellent druggable properties. Its molecular weight is 406.3870, conforming to the Lipinski rule, and a LogP value of 0.9760 indicates moderate lipid solubility, which facilitates cell membrane penetration. TPSA is 128.59 Ų, slightly above the ideal range, but still crosses the blood-brain barrier, meeting the needs of neurological drugs.
Moderate water solubility (0.3276), which is beneficial for the preparation and absorption of oral preparations. In vivo pharmacokinetic studies show that ginkgo lactone K has a high blood-brain barrier penetration rate and can effectively enter the central nervous system to exert its effects. Its metabolic pathway mainly involves liver enzyme systems, and the metabolites are safe.
In terms of safety, the hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test scored 0.9, indicating a low genotoxicity risk and meeting preclinical safety requirements.
However, the bioavailability and in vivo stability of ginkgo lactone K still need further optimization. In the future, its pharmacokinetic performance can be enhanced through drug carrier systems or structural modifications.
Ginkgo lactone K, as a natural product with multi-target neuroprotective effects, has broad clinical application prospects. Its potential efficacy in neurodegenerative diseases, ischemic brain injury, and neuroinflammation-related diseases provides important clues for the development of novel neuroprotective drugs.
Currently, ginkgo lactone K is still in basic research and early pharmacological evaluation stages, with relatively limited clinical research data. In the future, research on its pharmacokinetics, toxicology, and clinical safety should be strengthened to promote the development of clinical trials. At the same time, by integrating modern drug delivery technologies such as nanocarriers and brain-targeted drug delivery systems, their in vivo stability and targeting ability are enhanced.
In addition, structural modification and derivative development of ginkgo lactone K are also important directions, with the potential to obtain more efficient and safer neuroprotective drugs. The application of multi-omics techniques and systems biology will help deeply analyze its mechanisms of action and expand its indication range.
Ginkgo lactone K, as a representative active ingredient in ginkgo leaves, demonstrates highly promising medicinal value due to its unique chemical structure and multi-target neuroprotective effects. By regulating the AMPK/mTOR/ULK1 signaling pathway to induce protective autophagy and activate antioxidant and anti-inflammatory mechanisms, ginkgo lactone K effectively alleviates nerve damage and holds promising prospects for developing drugs for treating neurological diseases.
Although significant progress has been made in current research on ginkgo lactone K, its clinical application still faces challenges such as pharmacokinetic optimization, formulation development, and safety evaluation. In the future, by combining modern drug development technologies with multidisciplinary interdisciplinary research, Ginkgo Lactone K is expected to move from the laboratory to clinical practice, benefiting patients with neurological diseases.
Shenshuai
Wenjing
Hedandan
