Sim Ju Kyoung, Heo Ye Ji, Shin Jin Hak, Kim Seon Sook, Seo Su Ryeon
Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
Institute of Life Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
Pharmaceuticals (Basel). 2025 Jan 9;18(1):71. doi: 10.3390/ph18010071.
: , a bacterium residing in hair follicles, triggers acne by inducing monocyte-mediated inflammatory cytokine production. Gedunin, a limonoid derived from (commonly known as neem), is renowned for its antifungal, antimalarial, anticancer, anti-inflammatory, and neuroprotective effects. However, its role in mitigating -induced skin inflammation remains unexplored. This study investigates the anti-inflammatory effects of gedunin on -induced skin inflammation and elucidates the underlying mechanisms. : 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. : 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 -induced inflammation, primarily by targeting NF-κB signaling. : 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 -induced skin inflammation.
痤疮丙酸杆菌，一种存在于毛囊中的细菌，通过诱导单核细胞介导的炎性细胞因子产生引发痤疮。格杜宁，一种从印楝（俗称苦楝）中提取的柠檬苦素，以其抗真菌、抗疟疾、抗癌、抗炎和神经保护作用而闻名。然而，其在减轻痤疮丙酸杆菌诱导的皮肤炎症中的作用仍未被探索。本研究调查了格杜宁对痤疮丙酸杆菌诱导的皮肤炎症的抗炎作用，并阐明其潜在机制。方法：使用RAW 264.7小鼠巨噬细胞和小鼠骨髓来源的巨噬细胞（BMDMs）评估格杜宁的抗炎活性。评估关键炎性介质，包括白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）和白细胞介素-6（IL-6）。机制研究聚焦于核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路，以及含NOD样受体吡啉结构域3（NLRP3）炎性小体。采用体内痤疮模型检查格杜宁的治疗效果。结果：格杜宁显著降低RAW 264.7细胞中IL-1β、TNF-α、iNOS、COX-2和IL-6的表达。它抑制NF-κB激活，而不影响包括JNK/SAPK、ERK和p38 MAPK在内的MAPK信号通路。格杜宁还抑制BMDMs中NLRP3炎性小体的激活。在小鼠痤疮模型中，格杜宁主要通过靶向NF-κB信号通路有效减轻痤疮丙酸杆菌诱导的炎症。结论：格杜宁通过靶向关键炎性通路，特别是NF-κB信号通路，显示出作为痤疮治疗药物的潜力。本研究突出了格杜宁作为管理痤疮丙酸杆菌诱导的皮肤炎症的替代方法的前景。
