Journal List > J Nutr Health > v.48(4) > 1081400

J Nutr Health. 2015 Aug;48(4):319-326. Korean.
Published online August 31, 2015.
© 2015 The Korean Nutrition Society
Comparative effect of dietary borage oil and safflower oil on anti-proliferation and ceramide metabolism in the epidermis of essential fatty acid deficient guinea pigs
Se Ryung Lee and Yunhi Cho
Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi 446-701, Korea.

To whom correspondence should be addressed. tel: +82-31-201-3817, Email:
Received June 10, 2015; Revised July 07, 2015; Accepted July 24, 2015.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.



Borage oil (BO) and safflower oil (SO) are efficacious in reversing epidermal hyperproliferation, which is caused by the disruption of epidermal barrier. In this study, we compared the antiproliferative effect of dietary BO and SO. Altered metabolism of ceramide (Cer), the major lipid of epidermal barrier, was further determined by measurement of epidermal levels of individual Cer, glucosylceramide (GlcCer), and sphingomyelin (SM) species, and protein expression of Cer metabolizing enzymes.


Epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut diet (HCO) for 8 weeks. Subsequently, animals were fed diets of either BO (group HCO + BO) or SO (group HCO + SO) for 2 weeks. As controls, animals were fed BO (group BO) or HCO (group HCO) diets for 10 weeks.


Epidermal hyperproliferation was reversed in groups HCO + BO (67.6% of group HCO) and HCO + SO (84.5% of group HCO). Epidermal levels of Cer1/2, GlcCer-A/B, and β-glucocerebrosidase (GCase), an enzyme of GlcCer hydrolysis for Cer generation, were higher in group HCO + BO than in group HCO, and increased to levels similar to those of group BO. In addition, epidermal levels of SM1, serine palmitoyltransferase (SPT), and acidic sphingomyelinase (aSMase), enzymes of de novo Cer synthesis and SM hydrolysis for Cer generation, but not of Cer3-7, were higher in group HCO + BO than in group HCO. Despite an increase of SPT and aSMase in group HCO + SO to levels higher than in group HCO, epidermal levels of Cer1-7, GlcCer-A/B, and GCase were similar in these two groups. Notably, acidic ceramidase, an enzyme of Cer degradation, was highly expressed in group HCO + SO. Epidermal levels of GlcCer-C/D and SM-2/3 did not differ among groups.


Dietary BO was more prominent for reversing epidermal hyperproliferation by enhancing Cer metabolism with increased levels of Cer1/2, GlcCer-A/B, and SM1 species, and of GCase proteins.

Keywords: borage oil; safflower oil; epidermal hyperproliferation; ceramide metabolism


Fig. 1
Effect of dietary oils on epidermal proliferation in guinea pigs. (A) Histological appearance of epidermal proliferation in control guinea pigs fed the borage oil (BO) diet for 10 wks (group BO), and essential fatty acid (EFA) deficient guinea pigs fed the hydrogenated coconut oil (HCO) diet for 10 wks or 8 wks followed by feeding BO diet (group HCO + BO) or safflower oil (SO) diet (group HCO + SO) for 2 wks. Arrows indicate that the bottom layer of epidermis and epidermal proliferation is correlated with epidermal thickness from the arrow to the top. (B) Epidermal proliferation of guinea pigs fed different diets as indicated in A. Values are mean ± SEM (n = 4). Means with different letters indicate significant differences at p < 0.05 levels by one-way ANOVA and Tukey's honestly significant difference (HSD) post hoc test.
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Fig. 2
Altered expression of ceramide metabolic enzymes in control guinea pigs fed the borage oil (BO) diet for 10 wks (group BO), and essential fatty acid (EFA) deficient guinea pigs fed the hydrogenated coconut oil (HCO) diet for 10 wks or 8 wks followed by feeding BO diet (group HCO + BO) or safflower oil (SO) diet (group HCO + SO) for 2 wks. (A) Representative expressions of serine palmitoyltransferase (SPT), β-glucocerebrosidase (GCase), acid sphingomyelinase (aSMase) and acid ceramidase (aCDase) in epidermis of guinea pigs. Protein extracts (15 µg each) from groups BO, HCO, HCO + BO and HCO + SO were subjected to 8% sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotted with polyclonal antiserum against SPT (55 kDa), GCase (60 kDa), aSMase (75 kDa) or aCDase (55 kDa) and with actin (Santa Cruz, CA). (B) The signal intensities from multiple experiments of (A) were quantified, and the integrated areas were normalized, first to the corresponding value of actin and then to the signal observed in the normal control group (group BO). Values are mean ± SEM (n = 4). Means with different letters indicate significant differences at p < 0.05 levels by one-way ANOVA and Tukey's honestly significant difference (HSD) post hoc test. p < 0.01(**) between groups by unpaired Student's t-test.
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Table 1
Compositions of experimental diets
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Table 2
Fatty acid composition of dietary oils1)
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Table 3
Levels of ceramide, glucosylceramide and sphingomyelin species
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This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. HN13C0076).

1. Elias PM. Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 1983;80 1 Suppl:44s–49s.
2. Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991;24:1–26.
3. Harding CR. The stratum corneum: structure and function in health and disease. Dermatol Ther 2004;17 Suppl 1:6–15.
4. Hamanaka S, Hara M, Nishio H, Otsuka F, Suzuki A, Uchida Y. Human epidermal glucosylceramides are major precursors of stratum corneum ceramides. J Invest Dermatol 2002;119(2):416–423.
5. Uchida Y, Hara M, Nishio H, Sidransky E, Inoue S, Otsuka F, Suzuki A, Elias PM, Holleran WM, Hamanaka S. Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J Lipid Res 2000;41(12):2071–2082.
6. Gray GM, Yardley HJ. Lipid compositions of cells isolated from pig, human, and rat epidermis. J Lipid Res 1975;16(6):434–440.
7. Burr GO, Burr MM. Nutrition classics from The Journal of Biological Chemistry 82:345-67, 1929. A new deficiency disease produced by the rigid exclusion of fat from the diet. Nutr Rev 1973;31(8):248–249.
8. Wertz PW, Cho ES, Downing DT. Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat. Biochim Biophys Acta 1983;753(3):350–355.
9. Prottey C. Essential fatty acids and the skin. Br J Dermatol 1976;94(5):579–585.
10. Ziboh VA, Chapkin RS. Biologic significance of polyunsaturated fatty acids in the skin. Arch Dermatol 1987;123(12):1686a–1690.
11. Barre DE. Potential of evening primrose, borage, black currant, and fungal oils in human health. Ann Nutr Metab 2001;45(2):47–57.
12. Furse RK, Rossetti RG, Zurier RB. Gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory properties, blocks amplification of IL-1 beta production by human monocytes. J Immunol 2001;167(1):490–496.
13. Chung S, Kong S, Seong K, Cho Y. Gamma-linolenic acid in borage oil reverses epidermal hyperproliferation in guinea pigs. J Nutr 2002;132(10):3090–3097.
14. Cho Y, Ziboh VA. Nutritional modulation of guinea pig skin hyperproliferation by essential fatty acid deficiency is associated with selective down regulation of protein kinase C-beta. J Nutr 1995;125(11):2741–2750.
15. Mohrhauer H, Holman RT. The Effect of Dose Level of Essential Fatty Acids Upon Fatty Acid Composition of the Rat Liver. J Lipid Res 1963;4:151–159.
16. Kim Y, Song EH, Shin K, Lee Y, Cho Y. Dietary effect of silk protein on epidermal levels of free sphingoid bases and phosphate metabolites in NC/Nga mice. Korean J Nutr 2012;45(2):113–120.
17. Wang LJ, Chen SJ, Chen Z, Cai JT, Si JM. Morphological and pathologic changes of experimental chronic atrophic gastritis (CAG) and the regulating mechanism of protein expression in rats. J Zhejiang Univ Sci B 2006;7(8):634–640.
18. Takagi Y, Nakagawa H, Yaginuma T, Takema Y, Imokawa G. An accumulation of glucosylceramide in the stratum corneum due to attenuated activity of beta-glucocerebrosidase is associated with the early phase of UVB-induced alteration in cutaneous barrier function. Arch Dermatol Res 2005;297(1):18–25.
19. Uchida Y, Behne M, Quiec D, Elias PM, Holleran WM. Vitamin C stimulates sphingolipid production and markers of barrier formation in submerged human keratinocyte cultures. J Invest Dermatol 2001;117(5):1307–1313.
20. Mizutani Y, Mitsutake S, Tsuji K, Kihara A, Igarashi Y. Ceramide biosynthesis in keratinocyte and its role in skin function. Biochimie 2009;91(6):784–790.
21. Holleran WM, Takagi Y, Uchida Y. Epidermal sphingolipids: metabolism, function, and roles in skin disorders. FEBS Lett 2006;580(23):5456–5466.
22. Bartke N, Hannun YA. Bioactive sphingolipids: metabolism and function. J Lipid Res 2009;50 Suppl:S91–S96.
23. Ohnishi Y, Okino N, Ito M, Imayama S. Ceramidase activity in bacterial skin flora as a possible cause of ceramide deficiency in atopic dermatitis. Clin Diagn Lab Immunol 1999;6(1):101–104.
24. McCullough JL, Schreiber SH, Ziboh VA. Cell proliferation kinetics of epidermis in the essential fatty acid deficient rat. J Invest Dermatol 1978;70(6):318–320.
25. Tang W, Ziboh VA. Reversal of epidermal hyperproliferation in essential fatty acid deficient guinea pigs is accompanied by rapid generation of inositol triphosphate. Arch Dermatol Res 1988;280(5):286–292.
26. Kim J, Kim H, Jeong H, Kim SH, Park SK, Cho Y. Comparative effect of gromwell (Lithospermum erythrorhizon) extract and borage oil on reversing epidermal hyperproliferation in guinea pigs. Biosci Biotechnol Biochem 2006;70(9):2086–2095.
27. Lampe MA, Williams ML, Elias PM. Human epidermal lipids: characterization and modulations during differentiation. J Lipid Res 1983;24(2):131–140.
28. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, Lehmann JM. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A 1997;94:4318–4323.
29. McCusker MM, Grant-Kels JM. Healing fats of the skin: the structural and immunologic roles of the ω-6 and ω-3 fatty acids. Clin Dermatol 2010;28(4):440–451.
30. HogenEsch H, Boggess D, Sundberg JP. Changes in keratin and filaggrin expression in the skin of chronic proliferative dermatitis (cpdm) mutant mice. Pathobiology 1999;67(1):45–50.