This study was undertaken to identify a new combined plant extract (PAC) intended to treat in patients with acne vulgaris. We detected strong antibacterial activities of Pinus densiflora leaf extract (LP) against Propionibacterium acnes ( P. acnes ) and Staphylococcus epidermidis ( S. epidermidis ) and anti-inflammatory effect of Artemisia annua L. extract (AA). To develop more effective agent s in multiple targeting of the physiopathology of acne, a combination of three plant extracts (PAC), Pinus densiflora leaf extract (LP), Artemisia annua L. extract (AA), and Citrus junos fruit juice (FC), indicated anti-proliferative effect on P. acnes -induced HaCaT cells proliferation, was prepared mixing at ratio 2:1:1. PAC with MIC values of 2.25 mg/ml and 0.75 mg/ml against P. acnes and S. epidermidis was more active than LP (2.50 mg/ml and 1.00 mg/ml), was the most active of three extracts. PAC also showed more effective anti-inflammatory activity than a single plant extract in P. acnes -treated NF, HaCaT cells and LPS-treated Raw 264.7 cells. And then, we evaluated sebosuppressive effect of PAC on differentiation and lipogenesis of sebocytes. Results showed that PAC reduced sebum production and IGF-1-stimulated proliferation on sebocytes. In addition, PAC (final 2%) applied in a test product clinically decreased skin oil content, sebum output level, and the number of closed comedones and open comedones in a period of 4 weeks. The results of the studies demonstrate that PAC is clinically effective with anti-bacterial, anti-inflammatory, sebum protective properties for acne prone skin. These results suggest that in patients with acne, PAC can provide adjunctive care by targeting pathological factors including bacterial proliferation, inflammation and sebum production.
Whiting, D.A. (1979) Acne. The Western Journal of Medicine, 131, 551-557.
Zouboulis, C.C., Seltmann, H., Hiroi, N., Chen W., Young, M., Oeff, M., Scherbaum, W.A., Orfanos, C.E., McCann, S.M. and Bornstein, S.R. (2002) Corticotropin-Releasing Hormone: An Autocrine Hormone That Promotes Lipogenesis in Human Sebocytes. Proceedings of the National Academy of Sciences of the United States of America, 99, 7148-7153. https://doi.org/10.1073/pnas.102180999
Haider, A. and Shaw, J.C. (2004) Treatment of Acne Vulgaris. The Journal of the American Medical Association, 292, 726-735. https://doi.org/10.1001/jama.292.6.726
Toyoda, M. and Morohashi, M. (2001) Pathogenesis of Acne. Medical Electron Microscopy, 34, 29-40. https://doi.org/10.1007/s007950100002
Harper, J.C. and Thiboutot, D.M. (2003) Pathogenesis of Acne: Recent Research Advances. Advances in Dermatology, 19, 1-10.
Thiboutot, D. (2004) Regulation of Human Sebaceous Glands. Journal of Investigative Dermatology, 123, 1-12. https://doi.org/10.1111/j.1523-1747.2004.t01-2-.x
Kim, J., Ochoa, M.T., Krutzik, S.R., Takeuchi, O., Uematsu, S., Legaspi, A.J., Brightbill, H.D., Holland, D., Cunliffe, W.J., Akira, S., Sieling, P.A., Godowski, P.J. and Modlin, R.L. (2002) Activation of Toll-Like Receptor 2 in Acne Triggers Inflammatory Cytokine Responses. Journal of Immunology, 169, 1535-1541. https://doi.org/10.4049/jimmunol.169.3.1535
Jugeau, S., Tenaud, I., Knol, A.C., Jarrousse, V., Quereux, G., Khammari, A. and Dreno, B. (2005) Induction of Toll-Like Receptors by Propionibacterium acnes. British Journal of Dermatology, 153, 1105-1113. https://doi.org/10.1111/j.1365-2133.2005.06933.x
Kurokawa, I., Danby, F.W., Ju, Q., Wang, X., Xiang, L.F., Xia, L., Chen, WC., Nagy, I., Picardo, M., Suh, D.H., Ganceviciene, R., Schagen, S., Tsatsou, F. and Zouboulis C.C. (2009) New Developments in Our Understanding of Acne Pathogenesis and Treatment. Experimental Dermatology, 18, 821-832. https://doi.org/10.1111/j.1600-0625.2009.00890.x
Christos, C., Hristos, C. and Zouboulis, M.D. (2004) Acne and Sebaceous Gland Function. Clinics in Dermatology, 22, 360-366. https://doi.org/10.1016/j.clindermatol.2004.03.004
Cunliffe, W.J. (1989) Acne. Martin Dunitz, London.
Downing, D.T., Stewart, M.E. and Strauss, J.S. (1989) Changes in Sebum Secretion and the Sebaceous Gland. Clinics in Geriatric Medicine, 5, 109-114.
Smith, K.R. and Thiboutot, D.M. (2008) Sebaceous Gland Lipids: Friend or Foe? Journal of Lipid Research, 49, 271-281.
Zouboulis, C.C., Jourdan, E. and Picardo, M. (2014) Acne Is an Inflammatory Disease and Alterations of Sebum Composition Initiate Acne Lesions. Journal of the European Academy of Dermatology and Venereology, 28, 527-532. https://doi.org/10.1111/jdv.12298
Fritsh, M., Orfanos, C.E. and Zouboulis, C.C. (2001) Sebocytes Are the Key Regulators of Androgen Homeostasis in Human Skin. Journal of Investigative Dermatology, 116, 793-800.
Pappas, A. (2009) Epidermal Surface Lipids. Dermatoendocrinology, 1, 72-76. https://doi.org/10.4161/derm.1.2.7811
Rosenfield, R.L., Deplewski, D., Kentsis, A. and Ciletti, N. (1998) Mechanisms of Androgen Induction of Sebocyte Differentiation. Dermatology, 196, 43-46. https://doi.org/10.1159/000017864
Degitz, K., Placzek, M., Borelli, C. and Plewig, G. (2007) Pathophysiology of Acne. Journal der Deutschen Dermatologischen Gesellschaft, 5, 316-323. https://doi.org/10.1111/j.1610-0387.2007.06274.x
Deplewski, D. and Rosenfield, R.L. (1999) Growth Hormone and Insulin-Like Growth Factors Have Different Effects on Sebaceous Cell Growth and Differentiation. Endocrinology, 140, 4089-4094. https://doi.org/10.1210/endo.140.9.6957
Cappel, M., Mauger, D. and Thiboutot, D. (2005) Correlation between Serum Levels of Insulin-Like Growth Factor 1, Dehydroepiandrosterone Sulfate, and Dihydrotestosterone and Acne Lesion Count in Adult Women. Archives of Dermatology, 141, 333-338. https://doi.org/10.1001/archderm.141.3.333
Tasli, L., Turgut, S., Kacar, N., Ayada, C., Coban, M., Akcilar, R. and Ergin, S. (2013) Insulin-Like Growth Factor-I Gene Polymorphism in Acne Vulgaris. Journal of the European Academy of Dermatology and Venereology, 27, 254-257. https://doi.org/10.1111/j.1468-3083.2011.04299.x
Im, M., Kim, S.Y., Sohn, K.C., Choi, D.K., Lee, Y., Seo, Y.J., Kim, C.D., Hwang, Y.L., Zouboulis, C.C. and Lee, J.H. (2012) Epigallocatechin-3-Gallate Suppresses IGF-I-Induced Lipogenesis and Cytokine Expression in SZ95 Sebocytes. Journal of Investigative Dermatology, 132, 2700-2708. https://doi.org/10.1038/jid.2012.202
Van Aller, G.S., Carson, J.D., Tang, W., Peng, H., Zhao, L., Copeland, R.A., Tummino, P.J. and Luo, L. (2011) Epigallocatechin Gallate (EGCG), a Major Component of Green Tea, Is a Dual Phosphoinositide-3-kinase/mTOR Inhibitor. Biochemical and Biophysical Research Communications, 406, 194-199. https://doi.org/10.1016/j.bbrc.2011.02.010
Adams, J.C. and Morehart, A.L. (1982) Decline and Death of Pinus spp. in Delaware Caused by Bursaphelenchus xylophilus. Journal of Nematology, 14, 382-385.
Zhu, J., Gonda, Y., Yu, L., Li, F., Yan, Q. and Sun, Y. (2012) Regeneration of a Coastal Pine (Pinus thunbergii Parl.) Forest 11 Years after Thinning, Niigata, Japan. Public Library of Science One, 7, e47593.
Taniguchi, T., Kanzaki, N., Tamai, S., Yamanaka, N. and Futai, K. (2007) Does Ectomycorrhizal Fungal Community Structure Vary along a Japanese Black Pine (Pinus thunbergii) to Black Locust (Robinia pseudoacacia) Gradient? New Phytologist, 173, 322-334.
Won, J.N., Lee, S.Y., Song, D.S. and Poo, H. (2013) Antiviral Activity of the Plant Extracts from Thuja orientalis, Aster spathulifolius, and Pinus thunbergii against Influenza Virus A/PR/8/34. Journal of Microbiology and Biotechnology, 23, 125-130. https://doi.org/10.4014/jmb.1210.10074
Hong, S.S., Jeong, W., Kim, J.K., Kwon, J.G., Lee, J.Y., Ahn, E.K., Oh, J., Seo, D.W. and Oh, J.S. (2014) Neolignan Inhibitors of Antigen-Induced Degranulation in RBL-2H3 Cells from the Needles of Pinus thunbergii. Fitoterapia, 99, 347-351. https://doi.org/10.1016/j.fitote.2014.10.015
Deng, Y., Liu, Z. and Geng, Y. (2016) Anti-Allergic Effect Artemisia Extract in Rats. Experimental and Therapeutic Medicine, 12, 1130-1134. https://doi.org/10.3892/etm.2016.3361
Mueller, M.S., Runyambo, N., Wagner, I., Borrmann, S., Dietz, K. and Heide, L. (2004) Randomized Controlled Trial of a Traditional Preparation of Artemisia annua L. (Annual Wormwood) in the Treatment of Malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 98, 318-321. https://doi.org/10.1016/j.trstmh.2003.09.001
Klayman, D.L. (1985) Qinghaosu (Artemisinin): An Antimalarial Drug from China. Science, 228, 1049-1055. https://doi.org/10.1126/science.3887571
Zhao, Y.G., Wang, Y., Guo, Z., Gu, A.D., Dan, H.C., Baldwin, A.S., Hao, W. and Wan, Y.Y. (2012) Dihydroartemisinin Ameliorates Inflammatory Disease by Its Reciprocal Effects on Th and Regulatory T Cell Function via Modulating the Mammalian Target of Rapamycin Pathway. The Journal of Immunology, 189, 4417-4425. https://doi.org/10.4049/jimmunol.1200919
Radulović, N.S., Randjelović, P.J., Stojanović, N.M., Blagojević, P.D., Stojanović-Radić, Z.Z., Ilić, I.R. and Djordjević, V.B. (2013) Toxic Essential Oils. Part II: Chemical, Toxicological, Pharmacological and Microbiological Profiles of Artemisia annua L. Volatiles. Food and Chemical Toxicology, 58, 37-49. https://doi.org/10.1016/j.fct.2013.04.016
Wu, X., Zhang, W., Shi, X., An, P., Sun, W. and Wang, Z. (2010) Therapeutic Effect of Artemisinin on Lupus Nephritis Mice and Its Mechanisms. Acta Biochimica et Biophysica Sinica (Shanghai), 42, 916-923. https://doi.org/10.1093/abbs/gmq101
Bamunuarachchi, G.S., Ratnasooriya, W.D., Premakumara, S. and Udagama, P.V. (2013) Antimalarial Properties of Artemisia vulgaris L. Ethanolic Leaf Extract in a Plasmodium berghei Murine Malaria Model. Journal of Vector Borne Diseases, 50, 278-284.
Yoo, K.M., Lee, K.W., Park, J.B., Lee, H.J. and Hwang, I.K. (2004) Variation in Major Antioxidants and Total Antioxidant Activity of Yuzu (Citrus junos Sieb ex Tanaka) during Maturation and between Cultivars. Journal of Agricultural and Food Chemistry, 2, 5907-5913. https://doi.org/10.1021/jf0498158
Sawamura, M., Wu, Y., Fujiwara, C. and Urushibata, M. (2005) Inhibitory Effect of Yuzu Essential Oil on the Formation of N-Nitrosodimethylamine in Vegetables. Journal of Agricultural and Food Chemistry, 53, 4281-4287. https://doi.org/10.1021/jf047816u
Kim, S.H., Hur, H.J., Yang, H.J., Kim, H.J., Kim, M.J., Park, J.H., Sung, M.J., Kim, M.S., Kwon, D.Y. and Hwang, J.T. (2013) Citrus junos Tanaka Peel Extract Exerts Antidiabetic Effects via AMPK and PPAR-γ both In Vitro and In Vivo in Mice Fed a High-Fat Diet. Evidence-Based Complementary and Alternative Medicine, 2013, Article ID: 921012.
Shin, E.J., Park, J.H., Sung, M.J., Chung, M.Y. and Hwang, J.T. (2016) Citrus junos Tanaka Peel Ameliorates Hepatic Lipid Accumulation in HepG2 Cells and in Mice Fed a High-Cholesterol Diet. BMC Complementary and Alternative Medicine, 16, 499. https://doi.org/10.1186/s12906-016-1460-y
Konno, N. (2009) Mental Caring for Pre-Symptomatic Depression by Aroma—Effects of Lemon and Yuzu Essential Oil. Aroma Research, 39, 260-263.
Green, L.C., Wagner, D.A., Glogowski, J., Skipper, P.L., Wishnok, J.S. and Tannenbaum, S.R. (1982) Analysis of Nitrate, Nitrite, and [15N] Nitrate in Biological Fluids. Analytical Biochemistry, 126, 131-138. https://doi.org/10.1016/0003-2697(82)90118-X
Frosch, P.J. and Kligman, A.M. (1979) The Soap Chamber Test. A New Method for Assessing the Irritancy of Soaps. Journal of the American Academy of Dermatology, 1, 35-41. https://doi.org/10.1016/S0190-9622(79)70001-6
Graham, G.M., Farrar, M.D., Cruse-Sawyer, J.E., Holland, K.T. and Ingham, E. (2004) Proinflammatory Cytokine Production by Human Keratinocytes Stimulated with Propionibacterium acnes and GroEL. British Journal of Dermatology, 150, 421-428.
Nagy, I., Pivarcsi, A., Kis, K., Koreck, A., Bodai, L., McDowell, A., Seltmann, H., Patrick, S., Zouboulis, C.C. and Kemény, L. (2006) Propionibacterium acnes and Lipopolysaccharide Induce the Expression of Antimicrobial Peptides and Proinflammatory Cytokines/Chemokines in Human Sebocytes. Microbes and Infection, 8, 2195-2205. https://doi.org/10.1016/j.micinf.2006.04.001
Guin, J.D., Huber, D.S. and Gielerak, P.L. (1979) Antibiotic Sensitivity of Comedonal Propionibacterium acnes. Acta Dermato-Venereologica, 59, 552-554.
Jappe, U. (2003) Pathological Mechanisms of Acne with Special Emphasis on Propionibacterium acnes and Related Therapy. Acta Dermato-Venereologica, 83, 241-248. https://doi.org/10.1080/00015550310016463
Pretsch, A., Nagl, M., Schwendinger, K., Kreiseder, B., Wiederstein, M., Pretsch, D., Genov, M., Hollaus, R., Zinssmeister, D., Debbab, A., Hundsberger, H., Eger, A., Proksch, P. and Wiesner, C. (2014) Antimicrobial and Anti-Inflammatory Activities of Endophytic Fungi Talaromyces wortmannii Extracts against Acne-Inducing Bacteria. Public Library of Science One, 9, e97929. https://doi.org/10.1371/journal.pone.0097929
Trompezinski, S., Weber, S., Cadars, B., Larue, F., Ardiet, N., Chavagnac-Bonneville, M., Sayag, M. and Jourdan, E. (2016) Assessment of a New Biological Complex Efficacy on Dysseborrhea, Inflammation, and Propionibacterium acnes Proliferation. Clinical, Cosmetic and Investigational Dermatology, 9, 233-239. https://doi.org/10.2147/CCID.S110655
Yoon, J.Y., Kwon, H.H., Min, S.U., Thiboutot, D.M. and Suh, D.H. (2013) Epigallocatechin-3-Gallate Improves Acne in Humans by Modulating Intracellular Molecular Targets and Inhibiting P. acnes. Journal of Investigative Dermatology, 133, 429-440. https://doi.org/10.1038/jid.2012.292