Gedunin Mitigates <i>Cutibacterium acnes</i>-Induced Skin Inflammation by Inhibiting the NF-κB Pathway
<b>Background/Objectives</b>: <i>Cutibacterium acnes (C. acnes)</i>, a bacterium residing in hair follicles, triggers acne by inducing monocyte-mediated inflammatory cytokine production. Gedunin, a limonoid derived from <i>Azadirachta indica</i> (commonly known as...
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2025-01-01
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| author | Ju Kyoung Sim Ye Ji Heo Jin Hak Shin Seon Sook Kim Su Ryeon Seo |
| author_facet | Ju Kyoung Sim Ye Ji Heo Jin Hak Shin Seon Sook Kim Su Ryeon Seo |
| author_sort | Ju Kyoung Sim |
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| description | <b>Background/Objectives</b>: <i>Cutibacterium acnes (C. acnes)</i>, a bacterium residing in hair follicles, triggers acne by inducing monocyte-mediated inflammatory cytokine production. Gedunin, a limonoid derived from <i>Azadirachta indica</i> (commonly known as neem), is renowned for its antifungal, antimalarial, anticancer, anti-inflammatory, and neuroprotective effects. However, its role in mitigating <i>C. acnes</i>-induced skin inflammation remains unexplored. This study investigates the anti-inflammatory effects of gedunin on <i>C. acnes</i>-induced skin inflammation and elucidates the underlying mechanisms. <b>Methods</b>: 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-1β (IL-1β), tumor necrosis factor-α (TNF-α), 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-κB) 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’s therapeutic efficacy. <b>Results</b>: Gedunin significantly reduced the expression of IL-1β, TNF-α, iNOS, COX-2, and IL-6 in RAW 264.7 cells. It inhibited NF-κB 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 <i>C. acnes</i>-induced inflammation, primarily by targeting NF-κB signaling. <b>Conclusions</b>: Gedunin demonstrates potential as a therapeutic agent for acne treatment by targeting key inflammatory pathways, particularly NF-κB signaling. This study highlights gedunin’s promise as an alternative approach to managing <i>C. acnes</i>-induced skin inflammation. |
| format | Article |
| id | doaj-art-278485627f6648e6aee9b29324a35019 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-278485627f6648e6aee9b29324a350192025-01-24T13:45:16ZengMDPI AGPharmaceuticals1424-82472025-01-011817110.3390/ph18010071Gedunin Mitigates <i>Cutibacterium acnes</i>-Induced Skin Inflammation by Inhibiting the NF-κB PathwayJu Kyoung Sim0Ye Ji Heo1Jin Hak Shin2Seon Sook Kim3Su Ryeon Seo4Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of KoreaDepartment of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of KoreaDepartment of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of KoreaInstitute of Life Science, Kangwon National University, Chuncheon 24341, Republic of KoreaDepartment of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea<b>Background/Objectives</b>: <i>Cutibacterium acnes (C. acnes)</i>, a bacterium residing in hair follicles, triggers acne by inducing monocyte-mediated inflammatory cytokine production. Gedunin, a limonoid derived from <i>Azadirachta indica</i> (commonly known as neem), is renowned for its antifungal, antimalarial, anticancer, anti-inflammatory, and neuroprotective effects. However, its role in mitigating <i>C. acnes</i>-induced skin inflammation remains unexplored. This study investigates the anti-inflammatory effects of gedunin on <i>C. acnes</i>-induced skin inflammation and elucidates the underlying mechanisms. <b>Methods</b>: 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-1β (IL-1β), tumor necrosis factor-α (TNF-α), 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-κB) 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’s therapeutic efficacy. <b>Results</b>: Gedunin significantly reduced the expression of IL-1β, TNF-α, iNOS, COX-2, and IL-6 in RAW 264.7 cells. It inhibited NF-κB 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 <i>C. acnes</i>-induced inflammation, primarily by targeting NF-κB signaling. <b>Conclusions</b>: Gedunin demonstrates potential as a therapeutic agent for acne treatment by targeting key inflammatory pathways, particularly NF-κB signaling. This study highlights gedunin’s promise as an alternative approach to managing <i>C. acnes</i>-induced skin inflammation.https://www.mdpi.com/1424-8247/18/1/71<i>Cutibacterium acnes</i> (<i>C. acnes</i>)geduninskin inflammationNF-κBNLRP3 inflammasomeacne vulgaris |
| spellingShingle | Ju Kyoung Sim Ye Ji Heo Jin Hak Shin Seon Sook Kim Su Ryeon Seo Gedunin Mitigates <i>Cutibacterium acnes</i>-Induced Skin Inflammation by Inhibiting the NF-κB Pathway Pharmaceuticals <i>Cutibacterium acnes</i> (<i>C. acnes</i>) gedunin skin inflammation NF-κB NLRP3 inflammasome acne vulgaris |
| title | Gedunin Mitigates <i>Cutibacterium acnes</i>-Induced Skin Inflammation by Inhibiting the NF-κB Pathway |
| title_full | Gedunin Mitigates <i>Cutibacterium acnes</i>-Induced Skin Inflammation by Inhibiting the NF-κB Pathway |
| title_fullStr | Gedunin Mitigates <i>Cutibacterium acnes</i>-Induced Skin Inflammation by Inhibiting the NF-κB Pathway |
| title_full_unstemmed | Gedunin Mitigates <i>Cutibacterium acnes</i>-Induced Skin Inflammation by Inhibiting the NF-κB Pathway |
| title_short | Gedunin Mitigates <i>Cutibacterium acnes</i>-Induced Skin Inflammation by Inhibiting the NF-κB Pathway |
| title_sort | gedunin mitigates i cutibacterium acnes i induced skin inflammation by inhibiting the nf κb pathway |
| topic | <i>Cutibacterium acnes</i> (<i>C. acnes</i>) gedunin skin inflammation NF-κB NLRP3 inflammasome acne vulgaris |
| url | https://www.mdpi.com/1424-8247/18/1/71 |
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