{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T20:20:30Z","timestamp":1785788430157,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T00:00:00Z","timestamp":1647302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This work was carried out with the support of &quot;Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ015634)&quot; Rural Development Administration, Republic of Korea.","award":["PJ015634"],"award-info":[{"award-number":["PJ015634"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acne vulgaris is the most common disease of the pilosebaceous unit. The pathogenesis of this disease is complex, involving increased sebum production and perifollicular inflammation. Understanding the factors that regulate sebum production is important in identifying novel therapeutic targets for the treatment of acne. Bee Venom (BV) and melittin have multiple effects including antibacterial, antiviral, and anti-inflammatory activities in various cell types. However, the anti-lipogenic mechanisms of BV and melittin have not been elucidated. We investigated the effects of BV and melittin in models of Insulin-like growth factor-1 (IGF-1) or Cutibacterium acnes (C. acnes)-induced lipogenic skin disease. C. acnes or IGF-1 increased the expression of sterol regulatory element-binding protein-1 (SREBP-1) and proliferator-activated receptor gamma (PPAR-\u03b3), transcription factors that regulate numerous genes involved in lipid biosynthesis through the protein kinase B (Akt)\/mammalian target of rapamycin (mTOR)\/SREBP signaling pathway. In this study using a C. acnes or IGF-1 stimulated lipogenic disease model, BV and melittin inhibited the increased expression of lipogenic and pro-inflammatory factor through the blockade of the Akt\/mTOR\/SREBP signaling pathway. This study suggests for the first time that BV and melittin could be developed as potential natural anti-acne agents with anti-lipogenesis, anti-inflammatory, and anti-C. acnes activity.<\/jats:p>","DOI":"10.3390\/ijms23063152","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T03:34:13Z","timestamp":1647401653000},"page":"3152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Bee Venom and Its Major Component Melittin Attenuated Cutibacterium acnes- and IGF-1-Induced Acne Vulgaris via Inactivation of Akt\/mTOR\/SREBP Signaling Pathway"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3038-719X","authenticated-orcid":false,"given":"Hyemin","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, Catholic University of Daegu, Gyeongsan 42472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Jin","family":"An","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Catholic University of Daegu, Gyeongsan 42472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Gyeong","family":"Gwon","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Catholic University of Daegu, Gyeongsan 42472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongjae","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Catholic University of Daegu, Gyeongsan 42472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2329-4374","authenticated-orcid":false,"given":"Jaechan","family":"Leem","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Catholic University of Daegu, Gyeongsan 42472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-6049","authenticated-orcid":false,"given":"Sun-Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Catholic University of Daegu, Gyeongsan 42472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6840-4509","authenticated-orcid":false,"given":"Sang-Mi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Wanju 54875, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1646-2608","authenticated-orcid":false,"given":"Christos C.","family":"Zouboulis","sequence":"additional","affiliation":[{"name":"Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Faculty of Health Sciences Brandenburg, Auenweg 38, 06847 Dessau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan-Kyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Catholic University of Daegu, Gyeongsan 42472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1056\/NEJMcp033487","article-title":"Clinical practice. Acne","volume":"352","author":"James","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0140-6736(11)60321-8","article-title":"Acne vulgaris","volume":"379","author":"Williams","year":"2012","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1136\/bmj.325.7362.475","article-title":"Acne vulgaris","volume":"325","author":"Webster","year":"2002","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jin, S., and Lee, M.Y. (2018). Kaempferia parviflora Extract as a Potential Anti-Acne Agent with Anti-Inflammatory, Sebostatic and Anti-Propionibacterium acnes Activity. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113457"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/j.micinf.2006.04.001","article-title":"Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines\/chemokines in human sebocytes","volume":"8","author":"Nagy","year":"2006","journal-title":"Microbes Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.clindermatol.2004.03.004","article-title":"Acne and sebaceous gland function","volume":"22","author":"Zouboulis","year":"2004","journal-title":"Clin. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/ptr.6304","article-title":"Suppression of Propionibacterium acnes-stimulated proinflammatory cytokines by Chinese bayberry extracts and its active constituent myricetin in human sebocytes in vitro","volume":"33","author":"Chen","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1159\/000068476","article-title":"The role of innate immunity in the pathogenesis of acne","volume":"206","author":"Koreck","year":"2003","journal-title":"Dermatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12944-019-1072-x","article-title":"Active compound chrysophanol of Cassia tora seeds suppresses heat-induced lipogenesis via inactivation of JNK\/p38 MAPK signaling in human sebocytes","volume":"18","author":"Kwon","year":"2019","journal-title":"Lipids Health Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1194\/jlr.R700015-JLR200","article-title":"Thematic review series: Skin lipids. Sebaceous gland lipids: Friend or foe?","volume":"49","author":"Smith","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.jid.2016.12.031","article-title":"Inhibition of Sebum Production with the Acetyl Coenzyme A Carboxylase Inhibitor Olumacostat Glasaretil","volume":"137","author":"Hunt","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev-nutr-071714-034355","article-title":"The Roles of mTOR Complexes in Lipid Metabolism","volume":"35","author":"Caron","year":"2015","journal-title":"Annu. Rev. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1073\/pnas.93.3.1049","article-title":"Sterol regulation of acetyl coenzyme A carboxylase: A mechanism for coordinate control of cellular lipid","volume":"93","author":"Lopez","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1101\/gad.1212704","article-title":"Upstream and downstream of mTOR","volume":"18","author":"Hay","year":"2004","journal-title":"Genes Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.mce.2015.08.001","article-title":"Insulin and insulin-like growth factor-1 can modulate the phosphoinositide-3-kinase\/Akt\/FoxO1 pathway in SZ95 sebocytes in vitro","volume":"415","author":"Mirdamadi","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00424-011-0941-6","article-title":"\"Sebocytes\u2019 makeup\": Novel mechanisms and concepts in the physiology of the human sebaceous glands","volume":"461","author":"Toth","year":"2011","journal-title":"Pflugers. Arch."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/sj.jid.5701155","article-title":"IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase\/Akt pathway","volume":"128","author":"Smith","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0955-2235(94)90011-6","article-title":"Deciphering the MAP kinase pathway","volume":"5","year":"1994","journal-title":"Prog. Growth Factor Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0248-4900(93)90138-5","article-title":"MAP kinase kinase: A node connecting multiple pathways","volume":"79","author":"Mordret","year":"1993","journal-title":"Biol. Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.jaad.2006.08.048","article-title":"Guidelines of care for acne vulgaris management","volume":"56","author":"Strauss","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jaad.2009.01.019","article-title":"New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne group","volume":"60","author":"Thiboutot","year":"2009","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/embor.2009.12","article-title":"Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia?","volume":"10","author":"Ji","year":"2009","journal-title":"EMBO Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1038\/jid.2014.75","article-title":"The protective effects of melittin on Propionibacterium acnes-induced inflammatory responses in vitro and in vivo","volume":"134","author":"Lee","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4310","DOI":"10.1111\/bph.14487","article-title":"Therapeutic effects of bee venom and its major component, melittin, on atopic dermatitis in vivo and in vitro","volume":"175","author":"An","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0304-3959(96)03075-8","article-title":"The bee venom test: A new tonic-pain test","volume":"66","author":"Lariviere","year":"1996","journal-title":"Pain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.fct.2019.05.001","article-title":"Bee venom attenuates Porphyromonas gingivalis and RANKL-induced bone resorption with osteoclastogenic differentiation","volume":"129","author":"Gu","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/245163a0","article-title":"Letter: An anti-inflammatory peptide from bee venom","volume":"245","author":"Billingham","year":"1973","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.pharmthera.2007.04.004","article-title":"Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds","volume":"115","author":"Son","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10540-006-9030-z","article-title":"Melittin: A membrane-active peptide with diverse functions","volume":"27","author":"Raghuraman","year":"2007","journal-title":"Biosci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.3892\/ijmm.2015.2180","article-title":"Effects of bee venom against Propionibacterium acnes-induced inflammation in human keratinocytes and monocytes","volume":"35","author":"Kim","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1046\/j.1523-1747.1999.00771.x","article-title":"Establishment and characterization of an immortalized human sebaceous gland cell line (SZ95)","volume":"113","author":"Zouboulis","year":"1999","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00109-005-0715-8","article-title":"Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands","volume":"84","author":"Alestas","year":"2006","journal-title":"J. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/j.1600-0625.2009.00890.x","article-title":"New developments in our understanding of acne pathogenesis and treatment","volume":"18","author":"Kurokawa","year":"2009","journal-title":"Exp. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0031-3955(16)38158-5","article-title":"Acne vulgaris. Pathogenesis and treatment","volume":"38","author":"Winston","year":"1991","journal-title":"Pediatr. Clin. North. Am."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1046\/j.1365-2133.2004.05762.x","article-title":"Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL","volume":"150","author":"Graham","year":"2004","journal-title":"Br. J. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/S0002-9440(10)62479-0","article-title":"Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo","volume":"166","author":"Kang","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1038\/jid.2009.46","article-title":"Involvement of Propionibacterium acnes in the augmentation of lipogenesis in hamster sebaceous glands in vivo and in vitro","volume":"129","author":"Iinuma","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ryu, S., Han, H.M., Song, P.I., Armstrong, C.A., and Park, Y. (2015). Suppression of Propionibacterium acnes Infection and the Associated Inflammatory Response by the Antimicrobial Peptide P5 in Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132619"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1159\/000051771","article-title":"Is acne vulgaris a genuine inflammatory disease?","volume":"203","author":"Zouboulis","year":"2001","journal-title":"Dermatology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zouboulis, C.C. (2003). Sebaceous gland in human skin--the fantastic future of a skin appendage. J. Investig. Dermatol., 120.","DOI":"10.1046\/j.1523-1747.2003.12263.x"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e1375636","DOI":"10.1080\/19381980.2017.1375636","article-title":"Sebaceous-immunobiology is orchestrated by sebum lipids","volume":"9","author":"Szegedi","year":"2017","journal-title":"Dermato-endocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s12264-016-0024-y","article-title":"Melittin, the Major Pain-Producing Substance of Bee Venom","volume":"32","author":"Chen","year":"2016","journal-title":"Neurosci. Bull."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1038\/jid.2012.202","article-title":"Epigallocatechin-3-gallate suppresses IGF-I-induced lipogenesis and cytokine expression in SZ95 sebocytes","volume":"132","author":"Im","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1038\/jid.2015.29","article-title":"Activity-guided purification identifies lupeol, a pentacyclic triterpene, as a therapeutic agent multiple pathogenic factors of acne","volume":"135","author":"Kwon","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.jphs.2014.12.001","article-title":"Effect of oleoylethanolamide on diet-induced nonalcoholic fatty liver in rats","volume":"127","author":"Li","year":"2015","journal-title":"J. Pharmacol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Romano, A., Friuli, M., Del Coco, L., Longo, S., Vergara, D., Del Boccio, P., Valentinuzzi, S., Cicalini, I., Fanizzi, F.P., and Gaetani, S. (2021). Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARgamma\/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis. Nutrients, 13.","DOI":"10.3390\/nu13020394"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"120131","DOI":"10.1016\/j.lfs.2021.120131","article-title":"Quinizarin suppresses the differentiation of adipocytes and lipogenesis in vitro and in vivo via downregulation of C\/EBP-beta\/SREBP pathway","volume":"287","author":"Ree","year":"2021","journal-title":"Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/jid.2012.292","article-title":"Epigallocatechin-3-gallate improves acne in humans by modulating intracellular molecular targets and inhibiting P. acnes","volume":"133","author":"Yoon","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/jid.2013.334","article-title":"Propionibacterium acnes Induces an IL-17 Response in Acne Vulgaris that Is Regulated by Vitamin A and Vitamin D","volume":"134","author":"Agak","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.3892\/ijmm.2014.1933","article-title":"Inhibitory effects of bee venom on Propionibacterium acnes-induced inflammatory skin disease in an animal model","volume":"34","author":"An","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"d12","DOI":"10.2741\/A171","article-title":"Cytokines in acute and chronic inflammation","volume":"2","author":"Feghali","year":"1997","journal-title":"Front Biosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00403-014-1480-8","article-title":"Phytochemical modulation of the Akt\/mTOR pathway and its potential use in cutaneous disease","volume":"306","author":"Leo","year":"2014","journal-title":"Arch. Dermatol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"32111","DOI":"10.1074\/jbc.273.48.32111","article-title":"Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis","volume":"273","author":"Engelman","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3727\/000000006783981143","article-title":"Pu-erh tea supplementation suppresses fatty acid synthase expression in the rat liver through downregulating Akt and JNK signalings as demonstrated in human hepatoma HepG2 cells","volume":"16","author":"Chiang","year":"2005","journal-title":"Oncol. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/3152\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:36:47Z","timestamp":1760135807000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/3152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,15]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23063152"],"URL":"https:\/\/doi.org\/10.3390\/ijms23063152","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,15]]}}}