DERMAL EFFECTS OF UNSAPONIFIABLE COMPOUNDS 223 UNSAPONIFIABLE C OMPOUNDS OF PERILLA (PERILLA FRUTESCENS) SEED MEAL A study by Lee e t al. (69) focused on unsaponifi able compounds from perilla seed meal that were obtained after the production of perilla oil. Compositional analysis identifi ed 362.6 mg of total tocopherols, 3,761.4 mg of policosanol, 27,860.1 mg of phytosterols, and 1,028.2 mg of squalene in 100 g of unsaponifi able compounds. Tests on human der- mal fi broblasts showed, among other effects, decreased UVB-induced cytotoxicity, de- creased production of UVB-induced reactive oxygen species, decreased MMP production and c-Jun and c-Fos phosphorylation, and increased synthesis of collagen. These results indicate possible benefi ts in protection from photoaging processes. DISCUSSION Unsap onifi able c ompounds are an integral part of vegetable butters and oils in terms of their native chemical composition. Based on the reviewed in vitro and in vivo studies, we conclude that these substances contribute signifi cantly to the overall dermal effects of vegetable butters and oils. Recent experimen ts evaluating the antioxidative activity of total unsaponifi able com- pounds, i.e., not of individual components of unsaponifi able compounds, were published by Tavakoli’s group (70,71). Unsaponifi able matter of wild pistachio (Pistacia sp.), ses- ame, and rice bran oils was shown to have signifi cant antioxidative properties, which were stronger than that of the respective oils alone. To summarize, although direct evidence is scarce, it is reasonable to expect that antioxidative effects of unsaponifi able compounds may be expressed directly on the skin’s surface and in the epidermis. Similar conclusion can be drawn for the antimicrobial effects, as the human skin hosts an enormous world of microorganisms (72). Moreover, d ermally applied unsaponifi able compounds were found to benefi cially affect the function of surfactant-irritated skin (65). Detailed mechanisms of action were not investigated. However, phytosterols were suggested to play an important function by infl uencing the structure of epidermal lipids and regulating the skin’s barrier function. Authors assumed that phytosterols may have supplied SLS-damaged skin with depleted lipids. Some insight into this topic was highlighted in research performed by Menon et al. (73) who showed that SLS provoked a statistically signifi cant burst of synthesis of epidermal sterols. Dermally applied phytosterols or unsaponifi able compounds may therefore represent the additional supplementation of those compounds and help the skin’s own mechanisms to normalize barrier disruption more rapidly. However, Man et al. (74) showed that the dermal use of individual lipids (i.e., cholesterol, fatty acid, and ce- ramides) or incomplete mixtures of those lipids delay barrier recovery in acetone-treated mouse skin, in contrast to complete mixtures comprising all three lipids. This was as- sumed to originate at the level of lamellar bodies, which gave rise to abnormal intercel- lular membrane structures in the stratum corneum such abnormalities did not occur when a complete lipid mixture was provided. In addition to lipid-based structural im- provements of the epidermis, effects of unsaponifi able compounds were also observed in the dermis, at the level of protein composition and the improved elasticity of animal skin (64), and at the level of in vitro collagen synthesis (69). Finally, in terms of the skin’s overall functioning, hydration was shown to be signifi cantly improved by unsaponifi able compounds in a human clinical study (67).

JOURNAL OF COSMETIC SCIENCE 224 Dermal use of unsaponifi able compounds in the treatment of skin disorders is largely unexplored but has been recognized as promising according to two patents (75,76). De- spite the lack of direct evidence, it has been clearly emphasized that unsaponifi able com- pounds might contribute signifi cantly to an effective wound-healing action (2,27,77). It is, however, crucial to understand that in the treatment of wounds, fatty acids of triglyc- erides also play an important role (2). It is therefore reasonable to recommend the use of unrefi ned vegetable butters and oils because unsaponifi able compounds are removed dur- ing the refi ning process. Unsaponifi able compounds are also not very common in cosmetics. In contrast to a large number of vegetable butters and oils, only a few unsaponifi able compounds have been reported to be used as cosmetic ingredients in dermal formulations: unsaponifi able com- pounds from shea (Vitellaria paradoxa syn. Butyrospermum parkii) butter, canola (Brassica sp.) oil, soybean (Glycine max syn. Glycine soja) oil, sunfl ower (Helianthus annuus) oil, olive (Olea europaea) oil and hydrogenated olive oil, avocado (Persea americana syn. Persea gratis- sima) oil, sesame (Sesamum indicum) oil, and corn (Zea mays) oil (78). In the context of cosmetic use, the potential of permeation enhancement (68) and a corresponding safety profi le may have to be taken into account, as cosmetic products are typically used daily and over an extended period. However, more research is needed to draw reliable conclu- sions. Considering the current body of evidence, no critical concerns should be high- lighted, and unsaponifi able compounds have been assessed to be safe in typical concentrations and practices of use in cosmetics (78). CONCLUSION Studies prove that unsaponifi able compounds express benefi cial cosmetic and therapeutic effects after dermal application. It is therefore reasonable to recommend the use of unre- fi ned vegetable butters and oils, as well as unsaponifi able compounds alone, for the treat- ment and care of skin disorders. However, research in the area of dermal application of unsaponifi able compounds is very rare, and a call for in-depth studies seems to be of great interest. REFERENCES (1) D. Janeš and N. Kočevar Glavač, Eds., Modern Cosmetics, Ingredients of Natural Origin, a Scientifi c View, Vol. 1 (Širimo dobro besedo, Velenje, Slovenia., 2018). (2) N. Poljšak, S. Kreft, and N. Kočevar Glavač, Vegetable butters and oils in skin wound healing: scien- tifi c evidence for new opportunities in dermatology, Phyther. Res., 34, 254–269 (2019). (3) D. Fontanel, Unsaponifi able Matter in Plant Seed Oils (Springer Berlin Heidelberg, Berlin, Heidelberg, 2013). (4) “A n imal and Vegetable Fats and Oils — Determination of Unsaponifi able Matter — Method Using Hexane Extraction,” ISO/TC 34/SC 11 18609 (2000). (5) F. D. Gunstone, J. L. Harwood, and F. B. Padley, The Lipid Handbook, 2nd Ed., (Chapman & Hall, London, 1994). (6) J. Bruneton, Pharmacognosy, Phytochemistry, Medicinal Plants (Editions TEC & DOC, Paris, France 1999). (7) A. Cert, W. Moreda, and M. Pérez-Camino, Chromatographic analysis of minor constituents in vegeta- ble oils, J. Chromatogr. A., 881(1–2), 131–148 (2000). (8) P. Q . Tranchida, S. Salivo, F. A. Franchina, I. Bonaccorsi, P. Dugo, and L. Mondello, Qualitative and quantitative analysis of the unsaponifi able fraction of vegetable oils by using comprehensive 2D GC with dual MS/FID detection, Anal. Bioanal. Chem., 405(13), 4655–4663 (2013).