title: Activity-guided purification identifies lupeol, a pentacyclic triterpene, as a therapeutic agent multiple pathogenic factors of acne.
abstract: Acne vulgaris is a nearly universal cutaneous disease characterized by multifactorial pathogenic processes. Because current acne medications have various side effects, investigating new pharmacologically active molecules is important for treating acne. As natural products generally provide various classes of relatively safe compounds with medicinal potentials, we performed activity-guided purification after a series of screenings from the extracts of five medicinal plants to explore alternative acne medications. Lupeol, a pentacyclic triterpene, from the hexane extract of Solanum melongena L. (SM) was identified after instrumental analysis. Lupeol targeted most of the major pathogenic features of acne with desired physicochemical traits. It strongly suppressed lipogenesis by modulating the IGF-1R/phosphatidylinositide 3 kinase (PI3K)/Akt/sterol response element-binding protein-1 (SREBP-1) signaling pathway in SEB-1 sebocytes, and reduced inflammation by suppressing the NF-κB pathway in SEB-1 sebocytes and HaCaT keratinocytes. Lupeol exhibited a marginal effect on cell viability and may have modulated dyskeratosis of the epidermis. Subsequently, histopathological analysis of human patients' acne tissues after applying lupeol for 4 weeks demonstrated that lupeol markedly attenuated the levels of both the number of infiltrated cells and major pathogenic proteins examined in vitro around comedones or sebaceous glands, providing solid evidence for suggested therapeutic mechanisms. These results demonstrate the clinical feasibility of applying lupeol for the treatment of acne.
authors: Department of Dermatology, Seoul National University College of Medicine, Seoul, South Korea; Acne and Rosacea Research Laboratory, Seoul National University Hospital, Seoul, South Korea.
authors: Hyuck Hoon
authors: HH
authors: Kwon
authors: Acne and Rosacea Research Laboratory, Seoul National University Hospital, Seoul, South Korea.
authors: Ji Young
authors: JY
authors: Yoon
authors: Department of Dermatology, Seoul National University College of Medicine, Seoul, South Korea; Acne and Rosacea Research Laboratory, Seoul National University Hospital, Seoul, South Korea.
authors: Seon Yong
authors: SY
authors: Park
authors: Department of Dermatology, Seoul National University College of Medicine, Seoul, South Korea; Acne and Rosacea Research Laboratory, Seoul National University Hospital, Seoul, South Korea.
authors: Seonguk
authors: S
authors: Min
authors: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors: Yong-Il
authors: YI
authors: Kim
authors: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors: Ji Yong
authors: JY
authors: Park
authors: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors: Yun-Sang
authors: YS
authors: Lee
authors: Department of Dermatology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.
authors: Diane M
authors: DM
authors: Thiboutot
authors: Department of Dermatology, Seoul National University College of Medicine, Seoul, South Korea; Acne and Rosacea Research Laboratory, Seoul National University Hospital, Seoul, South Korea. Electronic address: daehun@snu.ac.kr.
authors: Dae Hun
authors: DH
authors: Suh
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy* / Q000473:pathology; D001688:Biological Products / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004817:Epidermis / Q000378:metabolism; D004952:Esters / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D050155:Lipogenesis; D016328:NF-kappa B / Q000378:metabolism; D053978:Pentacyclic Triterpenes / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*; D012629:Sebum / Q000166:cytology / Q000187:drug effects; D032322:Solanum / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry*; D000094042:Lupanes
chemical_list: D001688:Biological Products; D004952:Esters; D005227:Fatty Acids; D006586:Hexanes; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; C010480:lupeol; D000094042:Lupanes
references: Microbes Infect. 2006 Jul;8(8):2195-205
references: 16797202
references: Br J Dermatol. 2004 Mar;150(3):421-8
references: 15030323
references: BMC Dermatol. 2013 Sep 06;13:10
references: 24011352
references: J Pharm Sci. 2002 Jan;91(1):111-6
references: 11782902
references: Chem Pharm Bull (Tokyo). 2004 Oct;52(10):1242-5
references: 15467245
references: Biosci Biotechnol Biochem. 2012;76(1):183-5
references: 22232260
references: Cancer Res. 2007 Sep 15;67(18):8800-9
references: 17875721
references: J Invest Dermatol. 1996 Jan;106(1):176-82
references: 8592071
references: Am J Pathol. 2005 Jun;166(6):1691-9
references: 15920154
references: J Invest Dermatol. 2014 Jul;134(7):1922-30
references: 24496237
references: Life Sci. 2011 Feb 14;88(7-8):285-93
references: 21118697
references: Lancet. 2012 Jan 28;379(9813):361-72
references: 21880356
references: Dermatology. 1998;196(1):98-9
references: 9557240
references: Oncogene. 2009 Feb 26;28(8):1151-61
references: 19137016
references: J Invest Dermatol. 2008 May;128(5):1286-93
references: 17989724
references: J Am Acad Dermatol. 2009 May;60(5 Suppl):S1-50
references: 19376456
references: Life Sci. 2006 Feb 16;78(12):1329-35
references: 16216277
references: J Invest Dermatol. 2014 Feb;134(2):366-73
references: 23924903
references: Adv Dermatol. 2003;19:1-10
references: 14626815
references: J Control Release. 2003 Jan 9;86(1):69-92
references: 12490374
references: Food Chem Toxicol. 2010 Feb;48(2):549-52
references: 19932731
references: Dermatology. 2005;211(3):193-8
references: 16205063
references: J Am Acad Dermatol. 2007 Apr;56(4):651-63
references: 17276540
references: Mol Nutr Food Res. 2013 Nov;57(11):1950-8
references: 23836602
references: J Invest Dermatol. 2013 Feb;133(2):429-40
references: 23096708
references: Exp Dermatol. 2005 Feb;14(2):143-52
references: 15679586
references: J Clin Invest. 2008 Apr;118(4):1468-78
references: 18317594
references: J Biochem. 2005 Oct;138(4):467-72
references: 16272141
references: N Engl J Med. 2005 Apr 7;352(14):1463-72
references: 15814882
references: Cancer Cell Int. 2013 Nov 01;13(1):108
references: 24176221
references: EMBO Rep. 2009 Mar;10(3):194-200
references: 19229284
references: Carcinogenesis. 2005 Nov;26(11):1956-64
references: 15958516
references: Cancer Lett. 2009 Nov 28;285(2):109-15
references: 19464787
references: Biochem Biophys Res Commun. 2005 Oct 28;336(3):909-17
references: 16169525
references: Phytomedicine. 2008 Sep;15(9):763-7
references: 18222664
references: J Invest Dermatol. 2010 Apr;130(4):985-94
references: 20032992
references: Dermatoendocrinol. 2011 Jan;3(1):41-9
references: 21519409
references: Oncogene. 2004 Jul 1;23 (30):5203-14
references: 15122342
references: Nat Med. 2007 Aug;13(8):975-80
references: 17676051
references: Nature. 2004 Sep 23;431(7007):461-6
references: 15329734
references: Anal Biochem. 1993 May 15;211(1):139-43
references: 8323025
references: PeerJ. 2013 Feb 19;1:e40
references: 23638377
references: J Invest Dermatol. 2003 Jun;120(6):905-14
references: 12787114
references: Planta Med. 2009 Dec;75(15):1549-60
references: 19742422
references: Pharmacol Res. 2001 Feb;43(2):127-34
references: 11243713