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6-Gingerol
Synonym name:
Catalogue No.: BP0092
Cas No.: 23513-14-6
Formula: C17H26O4
Mol Weight: 294.391
Botanical Source: ginger (Zingiber officinale)
Purity: 90%~99%
Analysis Method: HPLC-DAD
Identification Method: Mass, NMR
Packing: Brown vial, HDPE plastic or Aluminum bottle
Can be supplied from milligrams, grams to kilograms.
The purity(assay) of 90%, 95% and 98% is available for food, nutrition and cosmetics request, except for R&D and reference standard.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
66.7600
3.3100
3.3100
Low
No
No
No
No
No
Negative
6-Gingerol, CAS number 23513-14-6, is one of the main active ingredients in fresh ginger (Zingiber officinale Roscoe) and belongs to the β-hydroxyketone class of natural products. As a typical secondary metabolite of ginger family plants, 6-gingerol has attracted attention for its diverse biological activities, especially demonstrating significant pharmacological potential in anti-inflammatory, antioxidant, anti-tumor, and metabolic regulation fields. In recent years, with advances in natural product pharmacology and molecular biology techniques, the mechanism of action of 6-gingerol has gradually been elucidated, involving multiple signaling pathways and molecular targets, demonstrating its unique advantages as a candidate molecule for multi-target drugs. This paper will systematically review the chemical structure and physicochemical properties of 6-gingerol, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and clinical application prospects, aiming to provide a theoretical foundation and reference for its subsequent drug development and clinical application.
The chemical name of 6-gingerol is 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)dec-3-one, with a molecular formula C17H26O4 and a molecular weight of 294.39. Its structural feature is a long-chain ketone body containing β-hydroxyl groups, with one position attached to a 4-hydroxy-3-methoxyphenyl aromatic ring, imparting its unique chemical and biological activity. 6-Gingerol belongs to the guaiacol and β-hydroxyketone families, featuring typical phenolic hydroxyl and methoxy functional groups, which play key roles in its antioxidant and free radical scavenging capabilities.
In terms of physicochemical properties, the LogP value of 6-gingerol is about 3.31, indicating moderate lipid solubility, which is beneficial for cell membrane penetration and bioavailability. Its topological polar surface area (TPSA) is 66.76 Ų, and it has 4 hydrogen bond acceptors, indicating certain hydrophilicity and binding ability in intermolecular interactions. Although its blood-brain barrier permeability is relatively low, it still possesses potential central nervous system activity. 6-Scavengol is not hepatotoxic or cardiotoxic; hERG channel inhibition and Ames-induced mutagenic tests are all negative, indicating high safety and a solid foundation for druggability.
6-gingerol is mainly found in the rhizomes of fresh ginger and is an important component of ginger volatile oils and non-volatile components. As a traditional Chinese medicine and seasoning, ginger is widely distributed across Asia, Africa, and the Caribbean. Its content is greatly affected by variety, harvest time, geographical environment, and processing method. Fresh ginger contains the highest content of 6-gingerol, while dried ginger and processed ginger products have lower content.
The main extraction methods for 6-gingerol include solvent extraction, supercritical fluid extraction, and modern green extraction technologies. Traditional solvent extraction mostly uses ethanol, water, or their mixed solvents, obtained by impregnation, reflux, or ultrasound-assisted extraction to obtain crude extracts, which are then purified and separated by silica gel column chromatography or high-performance liquid chromatography (HPLC). Supercritical CO2 extraction has been widely used in recent years due to its solvent-free nature, environmental friendliness, and high efficiency. In addition, microwave-assisted extraction and enzymatic hydrolysis-assisted extraction technologies are also used to improve extraction efficiency and purity. Optimizing the extraction process is crucial to ensure the content and stability of the active ingredient in 6-gingerol.
The pharmacological activities of 6-gingerol cover multiple aspects including anti-lipogenesis, anti-tumor, anti-invasive, antioxidant, anti-inflammatory, and pro-apoptosis effects, demonstrating its potential as a versatile natural medicine.
6-Gingerol significantly inhibits fat formation by regulating adipocyte differentiation and lipid metabolism. In vitro studies show that 6-gingerol can inhibit the differentiation of 3T3-L1 preadipocytes into mature adipocytes, mainly by downregulating key adipogenesis transcription factors PPARβ and C/EBPβ, thereby suppressing the expression of fatty acid synthase (FAS) and fatty acid-binding protein aP2. Additionally, 6-gingerol blocks adipocyte differentiation by weakening the activity of the Akt/GSK3β signaling pathway, suggesting its potential value in the prevention and treatment of metabolic diseases such as obesity and fatty liver.
6-Gingerol exhibits significant antiproliferative and pro-apoptotic activity across various tumor cell lines. Its anti-tumor mechanism involves regulation of cell cycle blocking and apoptosis signaling pathways. Research shows that 6-gingerol upregulates the atypical apoptosis-related gene NAG-1, inducing G1 phase cell cycle arrest, while downregulating cyclin D1 inhibits tumor cell proliferation. Its pro-apbotic effects also involve mitochondrial pathway activation, activation of caspase family proteins, and regulation of Bcl-2 family protein expression. Additionally, 6-gingerol can inhibit tumor cell invasion and migration, with some mechanisms related to the β-catenin signaling pathway, protein kinase Cβ (PKCβ), and glycogen synthase kinase-3β (GSK-3β).
As a natural phenolic compound, 6-gingerol has excellent free radical scavenging ability, effectively reducing oxidative stress damage. Its antioxidant effects are mainly achieved by directly scavenging reactive oxygen species (ROS) and upregulating endogenous antioxidant enzyme systems. In terms of anti-inflammation, 6-gingerol can inhibit the expression of pro-inflammatory cytokines (such as TNF-α, IL-6, IL-1β) and inflammatory mediators (such as NO, PGE2), regulate inflammatory signaling pathways like NF-κB and MAPK, reduce inflammatory responses, and demonstrate potential for treating chronic inflammatory diseases.
6-Gingerol has also shown positive effects in research on cognitive impairment and neurodegenerative diseases. Its targets include IDO1, APP, BACE1, PTPN1, TYR, ABCB1, ABCG2, SYNJ2, USP2, and ALOX5, involving multiple stages such as neuroinflammation, β-amyloid metabolism, and neuroprotection. Although the blood-brain barrier has low permeability, by modulating these targets, 6-gingerol may improve cognitive function and delay neurodegenerative changes.
The multiple pharmacological effects of 6-gingerol depend on its regulation of multiple cellular signaling pathways and key molecules. The specific mechanisms are as follows:
Cell cycle regulation: 6-gingerol upregulates NAG-1 (an atypical apoptosis-related gene) and blocks the G1 phase cell cycle, suppressing the expression of cyclin D1 and limiting cell proliferation.
Pro-apoptosis signaling: Activates mitochondria-dependent apoptosis pathways, regulates the Bcl-2/Bax ratio, promotes activation of caspase-3 and caspase-9, and induces tumor cell apoptosis.
Lipolysis inhibition: Downregulates lipolygeny transcription factors PPARβ and C/EBPβ, suppresses the expression of fatty acid synthase (FAS) and fatty acid-binding protein aP2, and blocks adipocyte differentiation. By inhibiting the Akt/GSK3β signaling pathway, it further influences fat metabolism.
Signaling pathway regulation: 6-Gingerol affects β-catenin, PKCβ, and GSK-3β pathways, modulating cell proliferation, differentiation, and migration.
Anti-inflammatory mechanism: Inhibits NF-κB and MAPK signaling pathways, reduces the expression of pro-inflammatory cytokines and mediators, and alleviates inflammatory responses.
Neuroprotective mechanism: By regulating targets such as IDO1, APP, and BACE1, it intervenes in neuroinflammation and β-amyloid metabolism, exerting cognitive protective effects.
The druggability parameters of 6-gingerol indicate that it has good potential for drug development. The molecular weight was 294.39, conforming to the Lipinski rule, and the LogP was 3.31, indicating moderate lipid solubility and favorable cell membrane penetration. TPSA is 66.76 Ų, with 4 hydrogen bond receptors, supporting effective binding to biological targets. The blood-brain barrier has low permeability, which may limit its direct role in central nervous system diseases, but it can be improved through structural modification or drug carrier technology.
Toxicological evaluation showed that 6-gingerol had no significant hepatotoxicity or cardiotoxicity, hERG channel inhibition and Ames-induced mutagenic tests were all negative, indicating good safety. In vivo pharmacokinetic studies show that 6-gingerol is well absorbed orally, but its bioavailability is limited by first-pass effects and metabolic stability. Its main metabolic pathways include phase I hydroxylation and phase II binding reactions (such as glucuronic acid binding), with most metabolites being water-soluble, easily excreted. In the future, drug formulation optimization and structural modification are expected to enhance its pharmacokinetic performance.
6-Gingerol, as a natural multifunctional active ingredient, has broad clinical application potential. Its anti-inflammatory, antioxidant, and metabolic regulation roles make it an ideal candidate for treating chronic inflammation, metabolic syndrome, and related diseases. Its antitumor activity offers new ideas for adjuvant therapy and prevention, especially in multi-target regulation of tumor cell proliferation, invasion, and metastasis.
In the field of neurodegenerative diseases and cognitive impairment, although the blood-brain barrier permeability is limited, 6-gingerol demonstrates neuroprotective potential by modulating multiple key targets. By combining nanocarriers and drug delivery systems, the bottleneck in drug delivery in the central nervous system is expected to be overcome in the future.
However, the clinical translation of 6-gingerol still faces many challenges, including low bioavailability, rapid metabolism in vivo, and insufficient targeting. Future research should focus on structural optimization, dosage form innovation, and combination drug strategies to enhance efficacy and safety. Moreover, systematic clinical trials validating its efficacy and safety are key steps in promoting 6-gingerol for clinical application.
As an important active ingredient in fresh ginger, 6-gingerol shows broad application prospects in areas such as anti-lipogenesis, anti-tumor, anti-inflammatory, and neuroprotective fields due to its multi-target and multi-mechanism pharmacological effects. Its excellent safety and drugfiability lay a solid foundation for subsequent drug development. In the future, by integrating modern medicinal chemistry, molecular biology, and pharmaceutics technologies, in-depth exploration of the mechanism of action of 6-gingerol and optimizing its pharmacokinetic properties will promote its clinical translation and benefit more patients.
Shenshuai
Wenjing
Hedandan
