Protective effects of volatile components of aged garlic extract against ultraviolet B-induced apoptosis in human skin fibroblasts
Kazuki Abe
Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri City, Japan
Healthcare Research and Development Division, Wakunaga Pharmaceutical Co. Ltd., Akitakata, Hiroshima, Japan
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Validation, Writing - original draft
Search for more papers by this authorKumiko Yamamoto
Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri City, Japan
Contribution: Data curation, Formal analysis, Investigation, Methodology
Search for more papers by this authorTakao Myoda
Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri City, Japan
Contribution: Conceptualization, Methodology, Project administration, Writing - review & editing
Search for more papers by this authorTakuto Fujii
Healthcare Research and Development Division, Wakunaga Pharmaceutical Co. Ltd., Akitakata, Hiroshima, Japan
Search for more papers by this authorCorresponding Author
Koichi Niwa
Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri City, Japan
Correspondence
Koichi Niwa, Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka Abashiri City Hokkaido 099-2493, Japan.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Writing - review & editing
Search for more papers by this authorKazuki Abe
Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri City, Japan
Healthcare Research and Development Division, Wakunaga Pharmaceutical Co. Ltd., Akitakata, Hiroshima, Japan
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Validation, Writing - original draft
Search for more papers by this authorKumiko Yamamoto
Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri City, Japan
Contribution: Data curation, Formal analysis, Investigation, Methodology
Search for more papers by this authorTakao Myoda
Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri City, Japan
Contribution: Conceptualization, Methodology, Project administration, Writing - review & editing
Search for more papers by this authorTakuto Fujii
Healthcare Research and Development Division, Wakunaga Pharmaceutical Co. Ltd., Akitakata, Hiroshima, Japan
Search for more papers by this authorCorresponding Author
Koichi Niwa
Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri City, Japan
Correspondence
Koichi Niwa, Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka Abashiri City Hokkaido 099-2493, Japan.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Writing - review & editing
Search for more papers by this authorAbstract
Aged garlic extract (AGE) has been shown to protect the skin against UV-induced damage, but effects of its volatile components remain unknown. We investigated the effects of the volatile fraction of AGE on the responses of cultured skin fibroblasts subjected to UV-B irradiation. UV-B irradiation (20 mJ/cm2) reduced the cell viability to 55% of control. The nonvolatile and volatile fractions of AGE inhibited the UV-B-induced reduction of cell viability; the cell viabilities were 100% and 73%, respectively. The volatile fraction inhibited the UV-B-induced increase in apoptotic cell death by 28%. The volatile fraction also inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) induced by UV-B irradiation. GC–MS analysis revealed that a large number of volatile compounds were generated during aging of garlic. These results suggest that the volatile fraction of AGE has protective effects against the UV-B-induced death of skin fibroblasts, and that this effect may partly be due to an inhibition of apoptosis via the downregulation of MAPK signaling. The volatile compounds of AGE may have beneficial applications for skin health.
Practical applications
In this study, we investigated the effects of AGE against cell damage of UV-B-irradiated human skin fibroblasts. The aging process of garlic produced characteristic volatile compounds that have significant protective effects against UV-induced cell damage. Our results demonstrated that the aging process is a suitable method to develop added value in garlic extracts to improve skin health.
CONFLICT OF INTEREST
There is no conflict of interest to declare.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- Abe, K., Hori, Y., & Myoda, T. (2020). Characterization of key aroma compounds in aged garlic extract. Food Chemistry, 312, 126081. https://doi.org/10.1016/j.foodchem.2019.126081
- Abe, K., Myoda, T., & Nojima, S. (2021). Identification and characterization of sulfur heterocyclic compounds that contribute to the acidic odor of aged garlic extract. Journal of Agricultural and Food Chemistry, 69(3), 1020–1026. https://doi.org/10.1021/acs.jafc.0c06634
- Adler, V., Schaffer, A., Kim, J., Dolan, L., & Ronai, Z. (1995). UV irradiation and heat shock mediate JNK activation via alternate pathways. Journal of Biological Chemistry, 270(44), 26071–26077. https://doi.org/10.1074/jbc.270.44.26071
- Amagase, H., Petesch, B. L., Matsuura, H., Kasuga, S., & Itakura, Y. (2001). Intake of garlic and its bioactive components. Journal of Nutrition, 131(3), 955S–962S. https://doi.org/10.1093/jn/131.3.955s
- Apalla, Z., Lallas, A., Sotiriou, E., Lazaridou, E., & Ioannides, D. (2017). Epidemiological trends in skin cancer. Dermatology Practical & Conceptual, 7(2), 1–6. https://doi.org/10.5826/dpc.0702a01
- Balmanno, K., & Cook, S. J. (2009). Tumour cell survival signalling by the ERK1/2 pathway. Cell Death and Differentiation, 16(3), 368–377. https://doi.org/10.1038/cdd.2008.148
- Banerjee, S. K., & Maulik, S. K. (2002). Effect of garlic on cardiovascular disorders: A review. Nutrition Journal, 1, 4. https://doi.org/10.1186/1475-2891-1-4
- Block, E., Naganathan, S., Putman, D., & Zhao, S.-H. (2007). Organosulfur chemistry of garlic and onion: Recent results. Pure and Applied Chemistry, 65(4), 625–632. https://doi.org/10.1351/pac199365040625
- Borrelli, F., Capasso, R., & Izzo, A. A. (2007). Garlic (Allium sativum L.): Adverse effects and drug interactions in humans. Molecular Nutrition & Food Research, 51(11), 1386–1397. https://doi.org/10.1002/mnfr.200700072
- Cagnol, S., & Chambard, J. C. (2010). ERK and cell death: Mechanisms of ERK-induced cell death—Apoptosis, autophagy and senescence. FEBS Journal, 277(1), 2–21. https://doi.org/10.1111/j.1742-4658.2009.07366.x
- Cho, Y.-C., Han, J.-B., & Park, S.-I. (2019). Photoprotective effects of soybean extract against uv-induced damage in human fibroblast and hairless mouse model. Journal of Animal Reproduction and Biotechnology, 34(1), 20–29. https://doi.org/10.12750/JARB.34.1.20
10.12750/JARB.34.1.20 Google Scholar
- Colín-González, A. L., Santana, R. A., Silva-Islas, C. A., Chánez-Cárdenas, M. E., Santamaría, A., & Maldonado, P. D. (2012). The antioxidant mechanisms underlying the aged garlic extract- and S-allylcysteine-induced protection. Oxidative Medicine and Cellular Longevity, 2012, 907162. https://doi.org/10.1155/2012/907162
- Edris, A. E. (2007). Pharmaceutical and therapeutic potentials of essential oils and their individual volatile constituents: A review. Phytotherapy Research, 21(4), 308–323. https://doi.org/10.1002/ptr.2072
- Engel, W., Bahr, W., & Schieberle, P. (1999). Solvent assisted flavour evaporation - a new and versatile technique for the careful and direct isolation of aroma compounds from complex food matrices. European Food Research and Technology, 209(3–4), 237–241. https://doi.org/10.1007/s002170050486
- Farage, M. A., Miller, K. W., Elsner, P., & Maibachà, H. I. (2008). Intrinsic and extrinsic factors in skin ageing: A review. International Journal of Cosmetic Science, 30(2), 87–95. https://doi.org/10.1111/j.1468-2494.2007.00415.x
- Farruk, M. R., Nissar, U.-A., Kaiser, P. J., Afnan, Q., Sharma, P. R., Bhushan, S., & Tasduq, S. A. (2015). Glycyrrhizic acid (GA) inhibits reactive oxygen species mediated photodamage by blocking ER stress and MAPK pathway in UV-B irradiated human skin fibroblasts. Journal of Photochemistry and Photobiology B: Biology, 148, 351–353. https://doi.org/10.1016/j.jphotobiol.2015.05.003
- Favaloro, B., Allocati, N., Graziano, V., Di Ilio, C., & De Laurenzi, V. (2012). Role of apoptosis in disease. Aging, 4(5), 330–349. https://doi.org/10.18632/aging.100459
- Fujisawa, H., Suma, K., Origuchi, K., Kumagai, H., Seki, T., & Ariga, T. (2008). Biological and chemical stability of garlic-derived allicin. Journal of Agricultural and Food Chemistry, 56(11), 4229–4235. https://doi.org/10.1021/jf8000907
- Ghosh, J., Das, J., Manna, P., & Sil, P. C. (2011). The protective role of arjunolic acid against doxorubicin induced intracellular ROS dependent JNK-p38 and p53-mediated cardiac apoptosis. Biomaterials, 32(21), 4857–4866. https://doi.org/10.1016/j.biomaterials.2011.03.048
- Giampieri, F., Alvarez-Suarez, L. M., Tulipani, S., Gonzàles-Paramàs, A. M., Santos-Buelga, C., Bompadre, S., Quiles, J. L., Mezzetti, B., & Battino, M. (2012). Photoprotective potential of strawberry (Fragaria × ananassa) extract against UV-A irradiation damage on human fibroblasts. Journal of Agricultural and Food Chemistgry, 60(9), 2322–2327. https://doi.org/10.1021/jf205065x
- Guy, G. P., Jr., Machlin, S. R., Ekwueme, D. U., & Yabroff, K. R. (2015). Prevalence and costs of skin cancer treatment in the U.S., 2002–2006 and 2007–2011. American Journal of Preventive Medicine, 48(2), 183–187. https://doi.org/10.1016/j.amepre.2014.08.036
- Iciek, M., Kwiecień, I., & Włodek, L. (2009). Biological properties of garlic and garlic-derived organosulfur compounds. Environmental and Molecular Mutagenesis, 50, 247–265. https://doi.org/10.1002/em.20474
- Kim, K. W., Kim, Y. T., Kim, M., Noh, B. S., & Choi, W. S. (2014). Effect of high hydrostatic pressure (HHP) treatment on flavor, physicochemical properties and biological functionalities of garlic. LWT - Food Science and Technology, 55(1), 347–354. https://doi.org/10.1016/j.lwt.2013.08.027
- Kim, S. R., Jung, Y. R., An, H. J., Kim, D. H., Jang, E. J., Choi, Y. J., Moon, K. M., Park, M. H., Park, C. H., Chung, K. W., Bae, H. R., Choi, Y. W., Kim, N. D., & Chung, H. Y. (2013). Anti-wrinkle and anti-inflammatory effects of active garlic components and the inhibition of MMPs via NF-κB signaling. PLoS ONE, 8(9), 1–12. https://doi.org/10.1371/journal.pone.0073877
- Kodera, Y., Ushijima, M., Amano, H., Suzuki, J. I., & Matsutomo, T. (2017). Chemical and biological properties of S-1-propenyl-L-cysteine in aged garlic extract. Molecules, 22(4), 570. https://doi.org/10.3390/molecules22040570
- Kuwabara, M., Asanuma, T., Niwa, K., & Inanami, O. (2008). Regulation of cell survival and death signals induced by oxidative stress. Journal of Clinical Biochemistry and Nutrition, 43(2), 51–57. https://doi.org/10.3164/jcbn.2008045
- Lawen, A. (2003). Apoptosis—An introduction. BioEssays, 25(9), 888–896. https://doi.org/10.1002/bies.10329
- Lee, H. J., Kim, J. S., Song, M. S., Seo, H. S., Moon, C., Kim, J. C., Jo, S. K., Jang, J. S., & Kim, S. H. (2009). Photoprotective effect of red ginseng against ultraviolet radiation-induced chronic skin damage in the hairless mouse. Phytotherapy Research, 23(3), 399–403. https://doi.org/10.1002/ptr.2640
- Markou, T., Dowling, A. A., Kelly, T., & Lazou, A. (2009). Regulation of Bcl-2 phosphorylation in response to oxidative stress in cardiac myocytes. Free Radical Research, 43(9), 809–816. https://doi.org/10.1080/10715760903071649
- Matsumura, Y., & Ananthaswamy, H. N. (2004). Toxic effects of ultraviolet radiation on the skin. Toxicology and Applied Pharmacology, 195(3), 298–308. https://doi.org/10.1016/j.taap.2003.08.019
- Matta, J. L., Ramos, J. M., Armstrong, R. A., & D'Antoni, H. (2005). Environmental UV-A and UV-B threshold doses for apoptosis and necrosis in human fibroblasts. Photochemistry and Photobiology, 81(3), 563–568. https://doi.org/10.1111/j.1751-1097.2005.tb00226.x
- Muthusamy, V., & Piva, T. J. (2010). The UV response of the skin: A review of the MAPK, NFκB and TNFα signal transduction pathways. Archives of Dermatological Research, 302(1), 5–17. https://doi.org/10.1007/s00403-009-0994-y
- Ngoc, L. T. N., Tran, V. V., Moon, J.-Y., Chae, M., Park, D., & Lee, Y.-C. (2019). Recent trends of sunscreen cosmetic: An update review. Cosmetics, 6(4), 64. https://doi.org/10.3390/cosmetics6040064
- Niwa, K., Inanami, O., Ohta, T., Ito, S., Karino, T., & Kuwabara, M. (2001). p38 MAPK and Ca2+ contribute to hydrogen peroxide-induced increase of permeability in vascular endothelial cells but ERK does not. Free Radical Research, 35(5), 519–527. https://doi.org/10.1080/10715760100301531
- Niwa, K., Inanami, O., Yamamori, T., Ohta, T., Hamasu, T., Karino, T., & Kuwabara, M. (2002). Roles of protein kinase C delta in the accumulation of P53 and the induction of apoptosis in H2O2-treated bovine endothelial cells. Free Radical Research, 36(11), 1147–1153. https://doi.org/10.1080/1071576021000016409
- Ohba, T., Ishisaka, M., Tsujii, S., Tsuruma, K., Shimazawa, M., Kubo, K., Umigai, N., Iwawaki, T., & Hara, H. (2016). Crocetin protects ultraviolet A—Induced oxidative stress and cell death in skin in vitro and in vivo. European Journal of Pharmacology, 789, 244–253. https://doi.org/10.1016/j.ejphar.2016.07.036
- Perde-Schrepler, M., Chereches, G., Brie, I., Tatomir, C., Postescu, I. D., Soran, L., & Filip, A. (2013). Grape seed extract as photochemopreventive agent against UVB-induced skin cancer. Journal of Photochemistry and Photobiology B: Biology, 118, 16–21. https://doi.org/10.1016/j.jphotobiol.2012.10.008
- Pérez-Köhler, B., García-Moreno, F., Bayon, Y., Pascual, G., & Bellón, J. M. (2015). Inhibition of Staphylococcus aureus adhesion to the surface of a reticular heavyweight polypropylene mesh soaked in a combination of chlorhexidine and allicin: An in vitro study. PLoS ONE, 10(5), 1–19. https://doi.org/10.1371/journal.pone.0126711
- Pillai, S., Oresajo, C., & Hayward, J. (2005). Ultraviolet radiation and skin aging: Roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation—A review. International Journal of Cosmetic Science, 27(1), 17–34. https://doi.org/10.1111/j.1467-2494.2004.00241.x
- Rana, S. V., Pal, R., Vaiphei, K., Sharma, S. K., & Ola, R. P. (2011). Garlic in health and disease. Nutrition Research Reviews, 24(1), 60–71. https://doi.org/10.1017/S0954422410000338
- Ray, B., Chauhan, N. B., & Lahiri, D. K. (2011). The “aged garlic extract” (AGE) and one of its active ingredients S-allyl-l-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's disease (AD). Current Medicinal Chemistry, 18(22), 3306–3313. https://doi.org/10.2174/092986711796504664
- Reeve, V. E., Bosnic, M., Rozinova, E., & Boehm-Wilcox, C. (1993). A garlic extract protects from ultraviolet B (280–320 nm) radiation-induced suppression of contact hypersensitivity. Photochemistry and Photobiology, 58(6), 813–817. https://doi.org/10.1111/j.1751-1097.1993.tb04975.x
- Rizwan, M., Rodriguez-Blanco, I., Harbottle, A., Birch-Machin, M. A., Watson, R. E. B., & Rhodes, L. E. (2011). Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: A randomized controlled trial. British Journal of Dermatology, 164(1), 154–162. https://doi.org/10.1111/j.1365-2133.2010.10057.x
- Saewan, N., & Jimtaisong, A. (2015). Natural products as photoprotection. Journal of Cosmetic Dermatology, 14(1), 47–63. https://doi.org/10.1111/jocd.12123
- Salehi, B., Zucca, B., Orhan, I. E., Azzini, E., Adetunji, C. O., Mohammed, S. A., Banerjee, S. K., Sharopov, F., Rigano, D., Sharifi-Rad, J., Armstrong, L., Martorell, M., Sureda, A., Martins, N., Selamoğlu, Z., & Ahmad, Z. (2019). Allicin and health: A comprehensive review. Trends in Food Science & Technology, 86, 502–516. https://doi.org/10.1016/j.tifs.2019.03.003
- Shaaban, H. A. E., El-Ghorab, A. H., & Shibamoto, T. (2012). Bioactivity of essential oils and their volatile aroma components: Review. Journal of Essential Oil Research, 24(2), 203–212. https://doi.org/10.1080/10412905.2012.659528
- Shen, H. M., & Liu, Z. G. (2006). JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radical Biology and Medicine, 40(6), 928–939. https://doi.org/10.1016/j.freeradbiomed.2005.10.056
- Shin, S. W., Jung, E., Kim, S., Kim, J. H., Kim, E. G., Lee, J., & Park, D. (2013). Antagonizing effects and mechanisms of afzelin against UVB-induced cell damage. PLoS ONE, 8(4), e61971. https://doi.org/10.1371/journal.pone.0061971
- Sui, X., Kong, N., Ye, L., Han, W., Zhou, J., Zhang, Q., Zhang, Q., He, H., & Pan, H. (2014). p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Letters, 344(2), 174–179. https://doi.org/10.1016/j.canlet.2013.11.019
- Svobodova, A., Walterova, D., & Vostalova, J. (2006). Ultraviolet light induced alteration to the skin. Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, 150(1), 25–38. https://doi.org/10.5507/bp.2006.003
- Takezawa, J., Ishimi, Y., & Yamada, K. (2008). Proteasome inhibitors remarkably prevent translesion replication in cancer cells but not normal cells. Cancer Science, 99(5), 863–871. doi:10.1111/j.1349-7006.2008.00764.x
- Tanaka, H., Murakami, Y., Ishii, I., & Nakada, S. (2009). Involvement of a forkhead transcription factor, FOXO1a, in UV-induced changes of collagen metabolism. Journal of Investigative Dermatology Symposium Proceedings, 14(1), 60–62. https://doi.org/10.1038/jidsymp.2009.2
- Tang, D., Wu, D., Hirao, A., Lahti, J. M., Liu, L., Mazza, B., Kidd, V. J., Mak, T. W., & Ingram, A. J. (2002). ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53. Journal of Biological Chemistry, 277(15), 12710–12717. https://doi.org/10.1074/jbc.M111598200
- Tanos, T., Marinissen, M. J., Leskow, F. C., Hochbaum, D., Martinetto, H., Gutkind, J. S., & Coso, O. A. (2005). Phosphorylation of c-Fos by members of the p38 MAPK family: Role in the AP-1 response to UV light. Journal of Biological Chemistry, 280(19), 18842–18852. https://doi.org/10.1074/jbc.M500620200
- United States Pharmacopeial Convention I. (2015). United States Pharmacopoeia 38 garlic fluid extract USP 38-NF 33; United States Pharmacopeial Convention (pp. 6052–6055).
- Wang, X., Martindale, J. L., & Holbrook, N. J. (2000). Requirement for ERK activation in cisplatin-induced apoptosis. Journal of Biological Chemistry, 275(50), 39435–39443. https://doi.org/10.1074/jbc.M004583200
- Xu, H., Yan, Y., Li, L., Peng, S., Qu, T., & Wang, B. (2010). Ultraviolet B-induced apoptosis of human skin fibroblasts involves activation of caspase-8 and -3 with increased expression of vimentin. Photodermatology, Photoimmunology & Photomedicine, 26(4), 198–204. https://doi.org/10.1111/j.1600-0781.2010.00522.x
- Zhang, J. A., Luan, C., Huang, D., Ju, M., Chen, K., & Gu, H. (2020). Induction of autophagy by baicalin through the AMPK-mTOR pathway protects human skin fibroblasts from ultraviolet B radiation-induced apoptosis. Drug Design, Development and Therapy, 14, 417–428. https://doi.org/10.2147/DDDT.S228047
- Zhou, H., Gao, J., Lu, Z. Y., Lu, L., Dai, W., & Xu, M. (2007). Role of c-Fos/JunD in protecting stress-induced cell death. Cell Proliferation, 40(3), 431–444. https://doi.org/10.1111/j.1365-2184.2007.00444.x
