γ-リノレン酸

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

174.1 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

174.5 Ų [M-H]-

This chemical does not meet GHS hazard criteria for 2.3% (1 of 43) of reports.

Warning

H315 (97.7%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 43 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: 6,9,12-Octadecatrienoic acid, (Z,Z,Z)-

6,9,12-Octadecatrienoic acid, (6Z,9Z,12Z)-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

D - Dermatologicals

QD - Dermatologicals

Gamolenic acid is converted to PGE1, which exhibits anti-inflammatory, antithrombotic, antiproliferative, and lipid-lowering effects. PGE1 also induces smooth muscle relaxation and vasodilation. Gamolenic acid is an essential component of membrane phospholipids, including the mitochondrial membrane, where it enhances the the integrity and the fluidity of the membrane. **Bone and joint health:** In a pilot study of women with a mean age of 79.5 years and senile osteoporosis, the use of gamolenic acid in combination with calcium and eicosapentaenoic acid was associated with an increase in femoral bone density and lumbar spine density in comparison to placebo, where there were no observable changes. In clinical studies of patients with rheumatoid arthritis, treatment with gamolenic acid-containing oils resulted in an improvement in symptoms, measured by joint tenderness counts and scores, joint swelling scores, physician global assessment, and pain. **Inflammation:** A study demonstrated that oral administration of gamolenic acid suppressed human T-cell proliferation and activation by interfering with early events in the TcR/CD3-receptor–mediated signal transduction cascade. **Atherosclerosis:** In ApoE genetic knock-out mice, dietary gamolenic acid was shown to reduce the average medial layer thickness of the vessel wall and reduces the size of atherosclerotic lesions. **Diabetic complications:** In a clinical trial of patients with mild diabetic neuropathy or distal diabetic neuropathy, treatment with gamolenic acid was associated with improved symptoms in hot and cold threshold, sensation, tendon reflexes, and muscle strength. GLA ameliorated the inflammatory profile in diabetic nephropathy in rat studies. **Cancer:** In three human tumor cell lines (the neuroblastoma CHP-212, the tubal carcinoma TG, and the colon carcinoma SW-620), gamolenic acid elicited cytotoxic effects in tumours by blocking cell proliferation following incorporation into malignant cells. In both clinical and animal studies of breast cancer, gamolenic acid, in combination with tamoxifen, down-regulated the expression of estrogen receptors. **Skin disorders:** In an open study of patients with atopic dermatitis, which is a disorder related to a deficiency of delta-6-desaturase and inefficient conversion of linoleic acid to gamolenic acid, daily administration of gamolenic acid was associated with a significant increase in plasma GLA and DGLA levels in combination with an improvement of clinical signs of atopic dermatitis. **Respiratory disorders:** In patients with acute lung injury or acute respiratory distress syndrome, gamolenic acid was shown to reduce cytokine production and neutrophil recruitment into the lung. In patients with atopic asthma, gamolenic acid blocked _ex vivo_ synthesis of leukotrienes from whole blood and isolated neutrophils compared to the placebo group.

Once gamolenic acid (GLA) is absorbed and converted to dihomo-gamolenic acid (DGLA), circulating DGLA fatty acids are converted to several lipid mediators with predominantly anti-inflammatory properties, such as prostaglandin-E1 (PGE1) and 15-HETrE. The anti-inflammatory effects of DGLA are attributed to both the anti-inflammatory properties of DGLA-derived metabolites and the ability of DGLA and its products to compete with arachidonic acid (AA) in the synthesis of pro-inflammatory potent eicosanoid products, such as prostaglandins, thromboxane and leukotrienes. Both PGE1 and 15-HETrE are known to suppress inflammation, promote vasodilation, lower blood pressure, inhibit smooth muscle cell proliferation, inhibit platelet aggregation, and exert anti-neoplastic activities. PGE1 is a potent vasodilator that binds to surface receptors on smooth muscle cells, increasing intracellular cAMP. PGE1 is binds to G protein coupled surface PGE (EP) receptors and prostacyclin (IP) receptors as a natural ligand. GLA is proposed to enhance calcium absorption, reduce excretion and increase calcium deposition in bone. It is proposed that GLA may suppress tumor growth _in vivo_ by increasing the expression of E-cadherin, a cell-to-cell adhesion molecule that acts as a suppressor of metastasis. Another possible mechanism of tumour suppression is that GLA also reduces tumor-endothelium adhesion, which is a key factor in the establishment of distant metastases, partly by improving gap junction communication within the endothelium. By targeting the inflammatory process involved in the pathogenesis of diabetic nephropathy, GLA inhibits the expression of inflammatory mediators that tend be elevated in diabetes, intracellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), thereby attenuates the recruitment and infiltration of monocytes or macrophages.

Via elongation mediated by elongase (ELOVL5), gamolenic acid is rapidly converted to dihomo-gamma-linolenic acid (DGLA), which is further cyclooxygenated to prostaglandin E1 (PGE1) via COX-1 or COX-2 enzymatic activity depending on the cell type. PGE1 may be metabolized to smaller prostaglandin remnants, primarily dicarboxylic acids, which undergo renal excretion. DGLA may be converted to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid (15-HETrE) by 15-lipoxygenase enzyme. Although the enzymatic pathway is less predominant relative to ELOVL5 in most cells, DGLA may also be converted to arachidonic acid (AA) via delta-5-desaturate activity, where hydrogen atoms are selectively removed to create new double bonds F27]. Arachidonic acid is a precursor in the biosynthesis of prostaglandin E2, thromboxanes, and leukotrienes, which are potent inflammatory mediators and play an important role in inflammatory pathways.

The findings from a pharmacokinetic study suggest that therapeutic levels of GLA can be achieved within a week. The fasting plasma GLA levels plateaued within seven days of beginning treatment, regardless of dose.

The metabolites of gamolenic acid is expected to undergo renal excretion.

No pharmacokinetic data available.

No pharmacokinetic data available.