J. Cosmet. Sci., 71, 65–75 (March/April 2020) 65 Synthesis of 5-Aminolevulinic Acid–Based ALACELL Possessing Inhibitory Effect against Cutibacterium acnes: Whitening Effect and Protective Effect of UVB-Irradiated Damage Cells HYUN-YOUNG KIM, SU-JUNG KIM, HWA-JUNG CHOI, and SOON-HO YIM , Department of Pharmaceutical Engineering, Dongshin University, Jeonnam, 58245 South Korea (H.-Y.K., S.-H.Y.), School of Biological Sciences and Biotechnology Graduate School, Chonnam National University , Gwangju, 61186 South Korea (S.-J.K.), Department of Beauty Science, Kwangju Women’s University, Gwangju 62396, South Korea (H.-J.C.) Accepted for publication January 23, 2020 . Synopsis Five-aminolevulinic acid (5-ALA)-photodynamic therapy combined with infrared radiation is an effective and safe therapy for facial acne. Although there are various available agents for treating acne, therapies for resistant or severe strains have been limited. The aim of this study was to investigate the inhibitory effi cacy of ALACELL synthesized by combining 5-ALA with Y-G-G-F-L peptide against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Yersinia enterocolitica, as well as Cutibacterium acnes. Furthermore, other effects of ALACELL on human skin cells, melanin formation, intracellular tyrosinase activity, and Ultra Violet B (UVB)- irradiated cell death were measured by treatment of ALACELL in vitro. ALACELL particularly showed a growth inhibitory effect on C. acnes and no inhibitory effect on the four bacteria strains. ALACELL reduced melanin formation and intracellular tyrosinase activity by α-melanin cell–stimulating hormone (α-MSH) in B16F10 cells, with no cytotoxicity. ALACELL also improved cell viability in UVB-irradiated HaCaT cells. The results of the experiment show that ALACELL exhibits more effi cacy than 5-ALA against antimicrobial activity, melanin formation, intracellular tyrosinase activity, and UVB-irradiated cell death. Therefore, ALACELL is recommended as a candidate for clinical application in the treatment of acne and skin aging and will be further investigated to study the mode of action and in actual situations. IN T RODUCTION Al l humans have a variety of micro-organisms on the skin that constitute the skin micro- biome and that might play a role in skin immunity and skin barrier (1). Systemic imbalances in this skin have been related to dermatologic disease problems, such as acne and atopic dermatitis (2). Address all correspondence to Soon-Ho Yim at virshyim@gmail.com . Hyun-Young Kim and Su-Jung Kim contributed equally to this work.
JOURNAL OF COSMETIC SCIENCE 66 Cu tibacterium acnes is a Gram-positive and anaerobic bacterium detected in human skin that has been reported to represent about 90% of the micro-organisms found on a typical adult’s face (3). However, C. acnes produces several enzymes that degrade skin constitu- ents as well as chemotactic factors that excite keratinocytes and inflammatory cells to release pro-inflammatory cytokines and reactive oxygen species (ROS) (4,5). Many studies have also shown that some genes among the C. acnes genome service the virulence of bac- teria and hence acne pathophysiology (6). Acne treatment using synthetic chemical drugs such as antibiotics and steroids can cause mild or severe side effects (7). Also, resistance of C. acnes against antimicrobials grew almost 40% between the 1980s and 2000s world- wide (8). Cell s responsible for skin pigmentation are committed to the regulation of melanogenesis (9). Reiterating exposure by ultraviolet (UV) irradiation leads to DNA damage in kerati- nocytes and induces production of the melanocyte-stimulating hormone (α-MSH). Even- tually, a UV-triggered pathway induces melanin synthesis and the transfer of melanosomes to keratinocytes (10). In East Asia, most women make efforts to reduce pigmentation and to improve skin lightening on their skin (11). The development of an effective whitening candidate to reduce toxicity and side effects from various materials is focused on with great interest in the cosmetic industry (12). However, active agents that exhibit inhibi- tory activity on melanogenesis have not been reported. There fore, a variety of research is focused on identifying the effectiveness of antibacterial or whitening properties that are preventative and therapeutically useful candidate mate- rials to treat microbial infections or photoreaction. Five-aminolevulinic acid (5-ALA) is a precursor for the synthetic processing of tetrapyrrole compounds and is used variously in medicine and agriculture fields (13). C. acnes synthesizes and stores porphyrins, and the porphyrins are endogenous photosensitive sources that absorb light energy within range of a specifi c wavelength range, but the amount of porphyrins made by C. acnes is relatively low (14). Therefore, to heal skin lesions, one might topically apply exogenous compounds such as 5-ALA (15). ALA-photodynamic therapy (PDT) has the potential to provide the only way of making better acne treatment by selectively eliminating defective piloseba- ceous units and killing C. acnes (16). In this process, energy is transferred from porphyrins to oxygen, and oxygen-reactive species such as singlet oxygen were generated, which ef- fectively oxidize molecules to generate cytotoxicity in epithelial cells (17,18). Therefore, an agent that possesses more antimicrobial activity than 5-ALA in C. acnes was synthesized by combining 5-ALA with Y-G-G-F-L peptide (ALACELL) in this study. It investigated the antimicrobial activities of ALACELL for Staphylococcus aureus, Bacillus cereus, Esche- richia coli, and Yersinia enterocolitica, as well as C. acnes. This study also investigated the whitening effect of ALACELL with the measurement of melanin formation and intracel- lular tyrosinase activity. Furthermore, it measured the recovery effect of cell damage in UVB-irradiated HaCaT cells. MATERIA LS AND METHODS CHEMICA LS AND REAGENTS 5-ALA w as purchased from Uniquemedicare Co., Ltd. (Gwangju-gwangyeoksi, South Korea). Phosphate-buffered saline (PBS), Trypsin-EDTA, fetal bovine serum (FBS), and Dulbecco’s
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