(cid:1) -Linolenic Acid in Borage Oil Reverses Epidermal Hyperproliferation in Guinea Pigs 1

As dietary sources of (cid:1) -linolenic acid [GLA; 18:3(n-6)], borage oil (BO; 24–25 g/100 g GLA) and evening primrose oil (PO; 8–10 g/100 g GLA) are efficacious in treating skin disorders. The triglycerol stereospecificity of these oils is distinct, with GLA being concentrated in the sn-2 position of BO and in the sn-3 position of PO. To determine whether the absolute level and/or the triglycerol stereospecificity of GLA in oils affect biological efficacy, epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut oil (HCO) diet for 8 wk. Subsequently, guinea pigs were fed diets of PO, BO or a mixture of BO and safflower oil (SO) for 2 wk. The mixture of BO and SO (BS) diet had a similar level of GLA as PO but with sn-2 stereospecificity. As controls, two groups were fed SO and HCO for 10 wk. Epidermal hyperproliferation was reversed by all three oils in the order of BO (cid:1) BS (cid:1) PO. However, proliferation scores of group PO were higher than of the normal control group, SO. The accumulations of dihomo- (cid:1) -linolenic acid [DGLA; 20:3(n-6)], an elongase product of GLA, into phospholipids and ceramides, of 15-hydroxyeicosatrienoic acid (15-HETrE), the potent antiproliferative metabolite of DGLA, and of ceramides, the major lipid maintaining epidermal barrier, in the epidermis of group BO were greater than of groups BS and PO. Group BS had higher levels of DGLA, 15-HETrE and ceramides than group PO. With primary dependence on absolute levels, our data demonstrate that the antiproliferative efficacy of GLA in the epidermis is preferably exerted from sn-2 stereospecificity of GLA in BO. J. Nutr. 132: 3090–3097, 2002.

[1]  K. Suzuki,et al.  Ceramide accumulation is associated with increased apoptotic cell death in cultured fibroblasts of sphingolipid activator protein-deficient mouse but not in fibroblasts of patients with Farber disease , 1999, Journal of Inherited Metabolic Disease.

[2]  V. Ziboh,et al.  Reversal of epidermal hyperproliferation in essential fatty acid deficient guinea pigs is accompanied by rapid generation of inositol triphosphate , 1988, Archives of Dermatological Research.

[3]  D. Barre Potential of Evening Primrose, Borage, Black Currant, and Fungal Oils in Human Health , 2001, Annals of Nutrition and Metabolism.

[4]  P. Elias,et al.  Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. , 2000, Journal of lipid research.

[5]  R. Chapkin,et al.  Reappraisal of the essential fatty acids.. , 2000 .

[6]  Stingl,et al.  Double‐blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema , 1999, The British journal of dermatology.

[7]  W. Jiang,et al.  Inhibition of angiogenic factor- and tumour-induced angiogenesis by gamma linolenic acid. , 1999, Prostaglandins, Leukotrienes and Essential Fatty Acids.

[8]  A. IJzerman,et al.  Role of ceramide 1 in the molecular organization of the stratum corneum lipids. , 1998, Journal of lipid research.

[9]  V. Ziboh,et al.  A novel 15-hydroxyeicosatrienoic acid-substituted diacylglycerol (15-HETrE-DAG) selectively inhibits epidermal protein kinase C-beta. , 1997, Biochimica et biophysica acta.

[10]  A. Fonteh,et al.  Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans. , 1997, The Journal of nutrition.

[11]  J. Dornan,et al.  Is evening primrose oil of value in the treatment of premenstrual syndrome? , 1996, Controlled clinical trials.

[12]  V. Ziboh,et al.  Nutritional modulation of guinea pig skin hyperproliferation by essential fatty acid deficiency is associated with selective down regulation of protein kinase C-beta. , 1995, Journal of NutriLife.

[13]  V. Ziboh,et al.  Incorporation of 13-hydroxyoctadecadienoic acid (13-HODE) into epidermal ceramides and phospholipids: phospholipase C-catalyzed release of novel 13-HODE-containing diacylglycerol. , 1994, Journal of lipid research.

[14]  R. Chapkin,et al.  Phospholipid sources of metabolically elongated gammalinolenic acid: Conversion to prostaglandin E1 in stimulated mouse macrophages , 1993 .

[15]  R. Chapkin,et al.  Mouse peritoneal macrophage prostaglandin E1 synthesis is altered by dietary gamma-linolenic acid. , 1992, The Journal of nutrition.

[16]  F. Bahmer ADASI score: atopic dermatitis area and severity index. , 1992, Acta dermato-venereologica. Supplementum.

[17]  C. Miller,et al.  Dietary supplementation with ethyl ester concentrates of fish oil (n-3) and borage oil (n-6) polyunsaturated fatty acids induces epidermal generation of local putative anti-inflammatory metabolites. , 1991, The Journal of investigative dermatology.

[18]  P. Wertz,et al.  Metabolism of linoleic acid in porcine epidermis. , 1990, Journal of lipid research.

[19]  C. Miller,et al.  Induction of epidermal hyperproliferation by topical n-3 polyunsaturated fatty acids on guinea pig skin linked to decreased levels of 13-hydroxyoctadecadienoic acid (13-hode). , 1990, The Journal of investigative dermatology.

[20]  Craig C. Miller,et al.  Dietary supplementation with oils rich in (n-3) and (n-6) fatty acids influences in vivo levels of epidermal lipoxygenase products in guinea pigs. , 1990, The Journal of nutrition.

[21]  D. Baker,et al.  Suppression of acute and chronic inflammation by dietary gamma linolenic acid. , 1989, The Journal of rheumatology.

[22]  P. Elias,et al.  Lipid content and lipid type as determinants of the epidermal permeability barrier. , 1989, Journal of lipid research.

[23]  C. Miller,et al.  Gammalinolenic acid-enriched diet alters cutaneous eicosanoids. , 1988, Biochemical and biophysical research communications.

[24]  P. Wertz,et al.  The time course of lipid biosynthesis in pig epidermis. , 1988, The Journal of investigative dermatology.

[25]  C. Miller,et al.  Oxidative metabolism of dihomogammalinolenic acid by guinea pig epidermis: evidence of generation of anti-inflammatory products. , 1988, Prostaglandins.

[26]  P. Wertz,et al.  Essential fatty acids and epidermal integrity. , 1987, Archives of dermatology.

[27]  V. Ziboh,et al.  Dietary influences of evening primrose and fish oil on the skin of essential fatty acid-deficient guinea pigs. , 1987, The Journal of nutrition.

[28]  J. Voorhees,et al.  Metabolism of essential fatty acids by human epidermal enzyme preparations: evidence of chain elongation. , 1986, Journal of lipid research.

[29]  M. Claeys,et al.  Metabolic profile of linoleic acid in porcine leukocytes through the lipoxygenase pathway. , 1985, Biochimica et biophysica acta.

[30]  U. Houtsmuller,et al.  Metabolism of linoleic acid and other essential fatty acids in the epidermis of the rat. , 1985, Biochimica et biophysica acta.

[31]  P. Wertz,et al.  Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat. , 1983, Biochimica et biophysica acta.

[32]  J. Søndergaard,et al.  Treatment of Rheumatoid Arthritis with Prostaglandin E1, Precursors CIS-Linoleic Acid and γ-Linolenic Acid , 1983 .

[33]  J. Burton,et al.  ORAL EVENING-PRIMROSE-SEED OIL IMPROVES ATOPIC ECZEMA , 1982, The Lancet.

[34]  D. Horrobin,et al.  TREATMENT OF ATOPIC ECZEMA WITH EVENING PRIMROSE OIL , 1981, The Lancet.

[35]  P. Ward,et al.  Suppression of chronic inflammation by evening primrose oil. , 1981, Progress in lipid research.

[36]  J. Taylor,et al.  A combined alkali extraction--ethidium bromide technique for the measurement of DNA in small pieces of tissue. , 1979, The Journal of investigative dermatology.

[37]  F. Mattson,et al.  The absorbability by rats of various triglycerides of stearic and oleic acid and the effect of dietary calcium and magnesium. , 1979, The Journal of nutrition.

[38]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.