Jesus Ana, Gimondi Sara, Pinho Sónia A, Ferreira Helena, Neves Nuno M, Palmeira Andreia, Sousa Emília, Almeida Isabel F, Cruz Maria T, Cidade Honorina
Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
UCIBIO-Applied Molecular Biosciences Unit, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Mar Drugs. 2025 Jul 2;23(7):278. doi: 10.3390/md23070278.
Skin aging is mainly caused by external factors like sunlight, which triggers oxidative stress and chronic inflammation. Natural halogenated flavonoids have demonstrated anti-inflammatory properties. Inspired by the macroalgae-derived bromophenol , we investigated the anti-inflammatory potential of structure-related chalcones (-). Chalcones and showed the least cytotoxicity in keratinocyte and macrophage cells. Chalcones , , , and exhibited the most significant anti-inflammatory effects in murine macrophages after lipopolysaccharide stimulation, with chalcone having the lowest IC value (≈0.58 μM). A SNAP assay confirmed that chalcones do not exert their effects through direct NO scavenging. Symmetrical bromine atoms and 3,4-dimethoxy groups on both aromatic rings improved the anti-inflammatory activity, indicating a relevant structure-activity relationship. Chalcones and were selected for study to clarify their mechanisms of action. At a concentration of 7.5 μM, chalcone demonstrated a rapid and effective inhibitory action on the protein levels of inducible nitric oxide synthase (iNOS), while chalcone exhibited a gradual inhibitory action. Moreover, chalcone effectively activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway with around a 3.5-fold increase at the end of 24 h at 7.5 μM, highlighting its potential as a modulator of oxidative stress responses. These findings place chalcone as a promising candidate for skincare products targeting inflammation and skin aging.
皮肤老化主要由阳光等外部因素引起，阳光会引发氧化应激和慢性炎症。天然卤代黄酮已显示出抗炎特性。受大型藻类衍生的溴酚启发，我们研究了结构相关查耳酮（-）的抗炎潜力。查耳酮 和 在角质形成细胞和巨噬细胞中表现出最小的细胞毒性。查耳酮 、 、 和 在脂多糖刺激后的小鼠巨噬细胞中表现出最显著的抗炎作用，其中查耳酮 的IC值最低（≈0.58 μM）。一项SNAP试验证实，查耳酮并非通过直接清除一氧化氮发挥作用。两个芳香环上的对称溴原子和3,4 -二甲氧基基团提高了抗炎活性，表明存在相关的构效关系。选择查耳酮 和 进行研究以阐明其作用机制。在浓度为7.5 μM时，查耳酮 对诱导型一氧化氮合酶（iNOS）的蛋白水平表现出快速有效的抑制作用，而查耳酮 表现出逐渐的抑制作用。此外，在7.5 μM浓度下，24小时结束时查耳酮 有效激活核因子红细胞2相关因子2（Nrf2）途径，增加约3.5倍，突出了其作为氧化应激反应调节剂的潜力。这些发现使查耳酮 成为针对炎症和皮肤老化的护肤品的有希望的候选物。
