Product name: α-Linolenic acid
Synonym name:
Catalogue No.: BP4133
Cas No.: 463-40-1
Formula: C18H30O2
Mol Weight: 278.436
Botanical Source:
Physical Description:
Type of Compound: Aliphatics
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.
For Reference Standard and R&D, Not for Human Use Directly.
HPLC of α-Linolenic acid
HNMR of α-Linolenic acid
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
37.3000
6.2239
3.8966
.0071
4.4791
3.2530
High
96.4360
2.5886
Yes
Yes
No
No
No
No
0.0
No
Yes
Yes
Yes
α-Linolenic acid (α-Linolenic acid, abbreviated as ALA, CAS No.: 463-40-1) is a typical plant-derived omega-3 polyunsaturated fatty acid, widely found in flaxseed oil, perilla oil, walnut oil, and various other vegetable oils. As one of the essential fatty acids for the human body, α-linolenic acid plays an important role in maintaining lipid metabolism, regulating inflammatory responses, and protecting cardiovascular health. In recent years, with the continuous rise in the incidence of cardiovascular and cerebrovascular diseases, components in natural products with cardiovascular protective effects have attracted increasing attention. α-linolenic acid, due to its unique chemical structure and physiological functions, has become an important subject for the research and development of new nutritional supplements and drugs.
This paper aims to systematically review the chemical structure and physicochemical properties of α-linolenic acid, its plant origins, and extraction methods, with a focus on its pharmacological activity and mechanism of action. Combined with the latest molecular target studies, it conducts an in-depth analysis of its druggability and pharmacokinetic characteristics, and finally discusses its potential for clinical applications and future research directions, providing comprehensive reference materials for the field of natural product pharmacology.
α-linolenic acid is a polyunsaturated fatty acid containing 18 carbon atoms, with a molecular formula of C18H30O2 and a molecular weight of 278.4360. Its structural feature is the presence of cis-(Z) double bonds at positions 9, 12, and 15 of the carbon chain, chemically named (9Z,12Z,15Z)-octadecocco-9,12,15-trienoic acid. This triple cis-double bond gives it unique chemical activity and biological functions.
In terms of physicochemical properties, α-linolenic acid exhibits high lipid solubility, with a LogP value of 6.2239, indicating strong lipophilicity, easy solubility in organic solvents, and extremely low water solubility (0.0071 mg/mL). Its polar surface area (TPSA) is 37.3 Ų, indicating that its overall molecular polarity is relatively low, which facilitates passive diffusion through the cell membrane. The high permeability of the blood-brain barrier suggests it may affect central nervous system function. It is worth noting that α-linolenic acid does not show hERG channel inhibition, and the Ames-induced mutagenic test result is 0.0, indicating high safety and low toxicological risk.
α-linolenic acid, as a type of fatty acid, has conjugate acids such as α-linolenate esters and (9Z,12Z,15Z)-octadeca-9,12,15-trienoate, which often exist in esterified forms in vegetable oils and fats and must be hydrolyzed to release free fatty acids to exert biological activity.
α-linolenic acid mainly comes from various plant seed oils rich in omega-3 fatty acids, with flaxseed oil having the highest content, accounting for about 50%-60% of total fatty acids. In addition, perilla (Perilla frutescens) seed oil, walnut (Juglans regia) oil, sunflower oil, and others also contain a certain proportion of α-linolenic acid.
Traditional extraction methods mostly use cold pressing and solvent extraction methods. The cold pressing method uses mechanical extrusion to avoid damage to fatty acid structures caused by high temperatures, preserving the high α-linolenic acid content and its natural active components. Solvent extraction commonly uses organic solvents such as hexane and ethanol, which have high extraction efficiency but require attention to solvent residues and the effects of heat treatment on fatty acid structure.
In recent years, supercritical CO2 extraction technology has become the preferred method for extracting α-linolenic acid, due to its gentle nature, absence of solvent residues, and strong selectivity. This technology effectively protects the cis double bond structure of α-linolenic acid, maximizing its biological activity.
The extracted raw materials usually undergo refining steps such as degumming, decolorization, and deodorization to remove impurities and unpleasant odors, resulting in high-purity α-linolenic acid oil products, suitable for the development of nutritional supplements and pharmaceutical formulations.
α-linolenic acid, as an important omega-3 fatty acid, possesses multiple biological activities, especially excelling in cardiovascular protection, anti-inflammation, antithrombotic effects, and metabolic regulation.
Numerous clinical and experimental studies have shown that α-linolenic acid can significantly reduce the risk of cardiovascular diseases. Its main mechanisms include regulating blood lipid levels, lowering low-density lipoprotein cholesterol (LDL-C), increasing high-density lipoprotein cholesterol (HDL-C), inhibiting platelet aggregation, improving vascular endothelial function, and reducing the formation of atherosclerosis.
Animal model studies show that supplementing with α-linolenic acid can alleviate atherosclerotic lesions induced by high-fat diets, lower plasma triglycerides and inflammatory factor levels, and improve vasodilatory function. In addition, α-linolenic acid can also regulate blood pressure-related signaling pathways and exert its antihypertensive effect.
α-linolenic acid plays a particularly significant role in antithrombotic effects. By inhibiting platelet activation and aggregation, it reduces thrombosis and thus lowers the incidence of myocardial infarction and stroke. Related studies have shown that α-linolenic acid can regulate the composition of platelet membrane lipids, affect intraplatelet calcium ion concentration and signal transduction, and ultimately inhibit the activity of thrombosis-related enzymes.
α-linolenic acid has strong anti-inflammatory activity, downregulating the expression of pro-inflammatory cytokines such as TNF-α and IL-6, inhibiting activation of the NF-κB signaling pathway, and alleviating chronic inflammatory states. Its metabolites also help regulate immune cell function, promote inflammation self-repair, and promote tissue regeneration.
As an important regulator of energy metabolism, α-linolenic acid can promote fatty acid oxidation, improve insulin sensitivity, and help prevent obesity and type 2 diabetes. Mouse metabolite studies show that α-linolenic acid affects the expression of genes related to lipid metabolism and regulates energy balance.
The multiple biological effects of α-linolenic acid depend on its interactions with various molecular targets, involving signal transduction, gene expression regulation, and cellular function regulation.
SELP-encoded P-selectin is expressed in platelets and endothelial cells, participating in inflammation and thrombosis processes. α-linolenic acid regulates SELF expression, reduces platelet adhesion to blood vessel walls, and inhibits thrombosis.
PPARG is a key regulator of lipid metabolism and inflammatory responses. α-linolenic acid, as a natural ligand of PPARG, can activate its signaling pathways, promote fatty acid oxidation, inhibit inflammatory gene expression, and improve metabolic syndrome.
ACEs play a central role in blood pressure regulation. α-linolenic acid exerts antihypertensive and vascular protective effects by inhibiting ACE activity, reducing angiotensin II production.
AKT1 is involved in cell survival, metabolism, and angiogenesis. α-linolenic acid activates the AKT1 signaling pathway, promoting endothelial cell function and vascular repair, and enhancing vascular elasticity.
ADRB2 regulates the cardiovascular system's stress response. α-linolenic acid improves myocardial function and vasodilatory capacity by regulating ADRB2 expression.
KCNH2 channels affect cardiac electrical activity and rhythm. α-linolenic acid does not inhibit KCNH2, indicating good cardiac safety.
NOS3 produces the vasodilatory factor nitric oxide (NO), which maintains vascular endothelial function. α-linolenic acid promotes NOS3 expression and activity, enhances NO production, and improves vasodilation.
ICAM1 and VCAM1 mediate adhesion between white blood cells and endothelial cells, which are important markers of inflammatory responses. α-linolenic acid inhibits the expression of these two molecules, reducing vascular inflammation.
SLC8A1 regulates intracellular calcium homeostasis and affects cardiomyocyte function. α-linolenic acid regulates SLC8A1, protecting myocardial cells from calcium overload damage.
In summary, α-linolenic acid achieves multiple pharmacological effects such as cardiovascular protection and anti-inflammation through multi-target and multi-pathway synergistic effects.
Druggability evaluation of α-linolenic acid shows good safety and bioavailability. It has a moderate molecular weight (278.4360) and high lipid solubility (LogP=6.2239), which is beneficial for oral absorption and cell membrane penetration. Low polarity surface area (TPSA=37.3) supports its good membrane permeability.
Its extremely low water solubility (0.0071 mg/mL) limits its solubility in aqueous environments and may affect the bioavailability of oral formulations, but it can be effectively improved through lipid carrier or nanoformulation technologies.
The high permeability of the blood-brain barrier suggests it may play a role in neurological diseases, but potential central nervous system side effects should be considered.
Toxicological evaluation showed that α-linolenic acid did not show hERG channel inhibition, reducing the risk of arrhythmias. Ames-induced mutagenic test was negative, indicating a low genotoxicity risk.
Pharmacokinetics, α-linolenic acid is mainly absorbed through the intestines into the bloodstream, then metabolized by the liver and involved in lipid metabolism. Its metabolites include precursors of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), further exerting biological activity. Its half-life is moderate, making it suitable for daily supplementation.
α-linolenic acid, as a safe and effective natural omega-3 fatty acid, has been widely used in the field of nutritional supplements, especially showing promising prospects in cardiovascular disease prevention and adjunctive treatment. Its multiple effects of antithrombotic, lipid-lowering, anti-inflammatory, and endothelial function improvement provide a natural treatment option for cardiovascular disease patients.
In the future, as molecular target research deepens, α-linolenic acid is expected to develop novel drugs targeting specific signaling pathways, especially with potential applications in metabolic syndrome, diabetes, and neurodegenerative diseases that are worth attention.
In addition, by utilizing modern formulation technologies such as liposomes, nanoparticles, and solid dispersions, the bioavailability and targeting of α-linolenic acid can be improved, further expanding its clinical application scope.
By combining genomics and metabolomics technologies, the study conducts an in-depth analysis of the interaction between α-linolenic acid and individual genetic background, helping to achieve precision nutrition and personalized treatment.
As an important plant-derived omega-3 fatty acid, α-linolenic acid shows broad application prospects in cardiovascular protection, anti-inflammation, and metabolic regulation due to its unique chemical structure and multi-target pharmacological effects. Its excellent druggability and safety provide a solid foundation for further development.
Future research should focus on in-depth analysis of its molecular mechanisms, development of novel formulations, and systematic evaluation of clinical efficacy, aiming to better convert α-linolenic acid into clinically usable natural medicines or functional nutritional supplements to benefit human health.
