{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:45:54Z","timestamp":1791895554943,"version":"4.3.4"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"MSIT (Ministry of Science and ICT) Korea","doi-asserted-by":"publisher","award":["IITP-2023-00260267"],"award-info":[{"award-number":["IITP-2023-00260267"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Cutibacterium acnes (C. acnes), a bacterium residing in hair follicles, triggers acne by inducing monocyte-mediated inflammatory cytokine production. Gedunin, a limonoid derived from Azadirachta indica (commonly known as neem), is renowned for its antifungal, antimalarial, anticancer, anti-inflammatory, and neuroprotective effects. However, its role in mitigating C. acnes-induced skin inflammation remains unexplored. This study investigates the anti-inflammatory effects of gedunin on C. acnes-induced skin inflammation and elucidates the underlying mechanisms. Methods: The anti-inflammatory activity of gedunin was assessed using RAW 264.7 mouse macrophage cells and mouse bone-marrow-derived macrophages (BMDMs). Key inflammatory mediators, including interleukin-1\u03b2 (IL-1\u03b2), tumor necrosis factor-\u03b1 (TNF-\u03b1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6), were evaluated. Mechanistic studies focused on the nuclear factor-kappa B (NF-\u03baB) and mitogen-activated protein kinase (MAPK) signaling pathways, along with the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. An in vivo acne model was employed to examine gedunin\u2019s therapeutic efficacy. Results: Gedunin significantly reduced the expression of IL-1\u03b2, TNF-\u03b1, iNOS, COX-2, and IL-6 in RAW 264.7 cells. It inhibited NF-\u03baB activation without affecting the MAPK pathways, including JNK\/SAPK, ERK, and p38 MAPK. Gedunin also suppressed the activation of the NLRP3 inflammasome in BMDMs. In the mouse acne model, gedunin effectively alleviated C. acnes-induced inflammation, primarily by targeting NF-\u03baB signaling. Conclusions: Gedunin demonstrates potential as a therapeutic agent for acne treatment by targeting key inflammatory pathways, particularly NF-\u03baB signaling. This study highlights gedunin\u2019s promise as an alternative approach to managing C. acnes-induced skin inflammation.<\/jats:p>","DOI":"10.3390\/ph18010071","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T07:59:42Z","timestamp":1736409582000},"page":"71","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Gedunin Mitigates Cutibacterium acnes-Induced Skin Inflammation by Inhibiting the NF-\u03baB Pathway"],"prefix":"10.3390","volume":"18","author":[{"given":"Ju Kyoung","family":"Sim","sequence":"first","affiliation":[{"name":"Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Ji","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-6225","authenticated-orcid":false,"given":"Jin Hak","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-6974","authenticated-orcid":false,"given":"Seon Sook","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Life Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4830-4965","authenticated-orcid":false,"given":"Su Ryeon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"},{"name":"Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000067817","article-title":"Epidemiology of Acne","volume":"206","author":"Dreno","year":"2003","journal-title":"Dermatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1136\/pgmj.75.884.328","article-title":"Acne: A review of immunologic and microbiologic factors","volume":"75","author":"Burkhart","year":"1999","journal-title":"Postgrad. 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