PI3K; Akt
α-Linolenic acid targets multiple signaling pathways and metabolic enzymes. It is converted to longer-chain omega-3 fatty acids via desaturation and elongation, which are incorporated into cell membranes, affecting membrane fluidity and signaling. It also serves as a ligand for nuclear receptors (PPARα, PPARγ) and inhibits inflammatory pathways by reducing the production of pro-inflammatory eicosanoids. It modulates the activity of enzymes like cyclooxygenase (COX) and lipoxygenase (LOX), leading to a shift from pro-inflammatory to anti-inflammatory mediators.

α-Linolenic acid converses into the longer chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)[1].
In vitro, α-linolenic acid demonstrates antioxidant and anti-inflammatory activities at concentrations of 10-100 µM. It reduces the secretion of TNF-α, IL-1β, and IL-6 in LPS-stimulated macrophages. It also decreases endothelial cell adhesion molecule expression and reduces monocyte adhesion. In cancer cell lines (e.g., breast, colon), it inhibits proliferation and induces apoptosis, with IC₅₀ values varying widely (20-200 µM). It also protects neuronal cells from oxidative stress and promotes neurite outgrowth.

In mice, α-Linolenic acid (50, 100, or 250 mg/kg; for 10 days) completely inhibits collagen- and adrenaline-induced thrombosis at 250 mg/kg[1]. Rats weighing 250–300 g have less A-V thrombus formation when given 35, 70, or 175 mg/kg of α-Linolenic acid[1]. In rats, α-Linolenic acid (70 or 175 mg/kg) inhibits collagen stimulated platelet aggregation[1].
In vivo, α-linolenic acid has been extensively studied in animal models and human populations. Dietary supplementation (e.g., 1-5 g/day in humans) has been associated with reduced risk of cardiovascular disease, lower blood pressure, and improved lipid profiles. In rodent models of colitis, arthritis, and neuroinflammation, α-linolenic acid reduces disease severity and inflammatory markers. It also supports cognitive function and may slow the progression of neurodegenerative disorders.

In vitro enzyme assays for α-linolenic acid involve measuring its effect on COX-1/2 and LOX activities using purified enzymes and chromogenic substrates. The compound's ability to reduce prostaglandin and leukotriene production is assessed. Its antioxidant capacity is measured using DPPH, ABTS, or ORAC assays. The fatty acid's effect on desaturase and elongase activities can be studied using radiolabeled precursor incorporation. Binding to PPARs is assessed in transactivation assays using reporter constructs.

In vitro cellular experiments for α-linolenic acid are performed using various cell lines (e.g., macrophages, endothelial cells, neuronal cells). Cells are treated with the fatty acid (1-200 µM) conjugated to albumin. The effect on cell viability, inflammatory cytokine secretion (ELISA/qPCR), adhesion molecule expression, and ROS generation is measured. The fatty acid's incorporation into membrane phospholipids is analyzed by GC-MS. Apoptosis is assessed by Annexin V staining.

Mice weighing at 18 ~ 22 g[1]
50, 100, 250 mg/kg
For 10 days
In vivo animal studies for α-linolenic acid are conducted in models of atherosclerosis, colitis, arthritis, and neurodegenerative diseases. Animals are fed diets supplemented with α-linolenic acid (e.g., 5-10% of total fat) or given oral gavage. Endpoints include organ histology, serum lipid profiles, inflammatory markers (cytokines, CRP), and behavioral tests. Tissues are analyzed for fatty acid composition, and gene expression studies are performed to assess the modulation of inflammatory and metabolic pathways.

The pharmacokinetic properties of α-linolenic acid show rapid absorption after oral ingestion, with peak plasma concentrations reached within 2-4 hours. It is metabolized in the liver via β-oxidation and desaturation/elongation to EPA and DHA. Its half-life is relatively short (hours) in plasma, but it accumulates in tissues, especially adipose tissue and cell membranes. It is excreted as CO₂ or urinary metabolites. The conversion efficiency to EPA and DHA is limited in humans (typically <5%).

Toxicity Summary
Alpha-linolenic acid (ALA) is considered an essential fatty acid because it is crucial for human health, but the human body cannot synthesize it. In fact, it is a plant-derived fatty acid. The human body can use ALA to synthesize other omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is a precursor to prostaglandins (3 series), leukotrienes (5 series), and thromboxanes (3 series). These eicosate compounds possess anti-inflammatory and anti-atherosclerotic properties. ALA metabolites can also inhibit the production of pro-inflammatory eicosate compounds prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), as well as pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Omega-3 fatty acids, such as alpha-linolenic acid (ALA) and its metabolites, can regulate the expression of various genes, including those involved in fatty acid metabolism and inflammation. They regulate gene expression by influencing the activity of transcription factors, such as NF-κB and members of the peroxisome proliferator-activated receptor (PPAR) family. ALA and its metabolites, when incorporated into the cell membrane, can affect membrane fluidity and may play a role in anti-inflammatory activity, inhibition of platelet aggregation, and the anti-proliferative effect of ALA. ALA is first metabolized to sterol tetrahydropyridine acid by Δ6 desaturase.
The toxicity profile of α-linolenic acid is excellent; it is a dietary nutrient and is considered safe even at high doses. No significant adverse effects have been reported in humans at intakes up to 10 g/day. In animal studies, no toxic effects were observed at high doses. It is not genotoxic or carcinogenic. However, high doses of any PUFA may cause gastrointestinal discomfort or bleeding risk due to antiplatelet effects, but these are rare at normal dietary levels.

[1]. Anti-thrombotic effects of α-linolenic acid isolated from Zanthoxylum bungeanum Maxim seeds. BMC Complement Altern Med. 2014 Sep 23;14:348.

Alpha-linolenic acid (ALA) is a clear, colorless liquid. (NTP, 1992)
Alpha-linolenic acid is an alpha-linolenic acid with cis double bonds at positions 9, 12, and 15. It has been shown to have antithrombotic effects. It is a micronutrient, a nutritional supplement, and a rodent metabolite. It is an omega-3 fatty acid, and also an alpha-linolenic acid. It is the conjugate acid of alpha-linolenic acid and (9Z,12Z,15Z)-octadecano-9,12,15-trienoic acid.
Alpha-linolenic acid (ALA) is a polyunsaturated omega-3 fatty acid. It is a component of many common plant oils and is essential for human nutrition.
Alpha-linolenic acid is found in or produced by Escherichia coli (K12 strain, MG1655 strain).
Alpha-linolenic acid has also been reported in tansina, kalodan tree, and other organisms with relevant data.
Alpha-linolenic acid is an essential fatty acid, belonging to the omega-3 fatty acid family. It is found in high concentrations in some plant oils and has been reported to inhibit prostaglandin synthesis, thereby reducing inflammation and preventing certain chronic diseases. Alpha-linolenic acid (ALA) is a polyunsaturated omega-3 fatty acid. It is a component of many common plant oils and is essential for human nutrition. A fatty acid found in plants and involved in prostaglandin formation. See also: cod liver oil (partial ingredients); evening primrose oil (partial ingredients); krill oil (partial ingredients)... See more...

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Pharmacological Indications
For nutritional supplementation and treatment of dietary deficiencies or imbalances.

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Mechanism of Action
Alpha-linolenic acid (ALA) is considered an essential fatty acid because it is crucial for human health, but the body cannot synthesize it. In fact, it is a plant-derived fatty acid. The body can use ALA to synthesize other omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is a precursor to prostaglandins, leukotrienes, and thromboxanes. These eicosate compounds possess anti-inflammatory and anti-atherosclerotic properties. ALA metabolites may inhibit the production of pro-inflammatory eicosate compounds prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), as well as pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). ω-3 fatty acids (such as ALA and its metabolites) can regulate the expression of various genes, including those involved in fatty acid metabolism and inflammation. They regulate gene expression by influencing the activity of transcription factors, including NF-κB and members of the peroxisome proliferator-activated receptor (PPAR) family. ALA and its metabolites, when incorporated into the cell membrane, can affect membrane fluidity and may play a role in anti-inflammatory activity, inhibition of platelet aggregation, and the anti-proliferative effect of ALA. ALA is first metabolized to sterol acids by Δ6 desaturase.

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Pharmacodynamics
α-Linolenic acid (ALA) is an 18-carbon polyunsaturated fatty acid containing three double bonds.
Also known as omega-3 fatty acids, it is an essential nutrient for all mammals. Ingesting alpha-linolenic acid (or omega-3 fatty acids) can reduce the risk of cardiovascular disease by: 1) preventing arrhythmias that can lead to sudden death; 2) reducing the risk of blood clots (thrombosis) that can lead to heart attack or stroke; 3) lowering serum triglyceride levels; 4) slowing the growth of atherosclerotic plaques; 5) improving vascular endothelial function; 6) slightly lowering blood pressure; and 7) reducing inflammation. ALA deficiency can lead to vision problems and sensory neuropathy. It may also cause scaly, bleeding skin or scalp inflammation.
α-Linolenic acid is an essential omega-3 fatty acid with well-established health benefits, particularly for cardiovascular and inflammatory diseases. It is a precursor to longer-chain omega-3s and plays a role in maintaining cell membrane integrity and function. It is widely available as a dietary supplement and is considered a functional food ingredient. Its therapeutic applications are being explored in the context of metabolic syndrome, neurodegenerative diseases, and immune disorders. It is not a drug but a nutritional compound that contributes to disease prevention and overall health.

C₁₈H₃₀O₂

278.43

278.224

463-40-1

463-40-1

5280934

Colorless to light yellow liquid

0.9±0.1 g/cm3

443.4±0.0 °C at 760 mmHg

-11 °C(lit.)

275.7±14.4 °C

0.0±2.3 mmHg at 25°C

1.491

6.5

1

2

13

20

301

0

O([H])C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C(/[H])=C(/[H])\C([H])([H])/C(/[H])=C(/[H])\C([H])([H])/C(/[H])=C(/[H])\C([H])([H])C([H])([H])[H])=O

DTOSIQBPPRVQHS-PDBXOOCHSA-N

InChI=1S/C18H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h3-4,6-7,9-10H,2,5,8,11-17H2,1H3,(H,19,20)/b4-3-,7-6-,10-9-

(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid

αLinolenic acid α Linolenic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol: ~100 mg/mL (~359.2 mM)
DMSO: ~100 mg/mL (~359.2 mM)
H2O: <0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.98 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.98 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.98 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)