Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea.
Department of Ophthalmology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Republic of Korea.
Int J Mol Sci. 2023 May 10;24(10):8537. doi: 10.3390/ijms24108537.
In this study, the potential protective effects of cirsilineol (CSL), a natural compound found in , were examined on lipopolysaccharide (LPS)-induced inflammatory responses. CSL was found to have antioxidant, anticancer, and antibacterial properties, and was lethal to many cancer cells. We assessed the effects of CSL on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). We also examined the effects of CSL on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in the pulmonary histological status of LPS-injected mice. The results showed that CSL increased HO-1 production, inhibited luciferase-NF-κB interaction, and reduced COX-2/PGE2 and iNOS/NO levels, leading to a decrease in signal transducer and activator of transcription (STAT)-1 phosphorylation. CSL also enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and reduced IL-1β expression in LPS-treated HUVECs. We found that CSL's suppression of iNOS/NO synthesis was restored by inhibiting HO-1 through RNAi. In the animal model, CSL significantly decreased iNOS expression in the pulmonary biostructure, and TNF-α level in the bronchoalveolar lavage fluid. These findings indicate that CSL has anti-inflammatory properties by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, CSL may have potential as a candidate for developing new clinical substances to treat pathological inflammation.
在这项研究中，研究人员考察了天然化合物齿叶乳香酸（CSL）对脂多糖（LPS）诱导的炎症反应的潜在保护作用。CSL 具有抗氧化、抗癌和抗菌特性，对许多癌细胞具有致死作用。我们评估了 CSL 对 LPS 激活的人脐静脉内皮细胞（HUVEC）中血红素加氧酶（HO）-1、环氧化酶（COX）-2 和诱导型一氧化氮合酶（iNOS）的影响。我们还研究了 CSL 对 LPS 注射小鼠肺部组织学中 iNOS、肿瘤坏死因子（TNF）-α 和白细胞介素（IL）-1β表达的影响。结果表明，CSL 增加了 HO-1 的产生，抑制了荧光素酶-NF-κB 相互作用，降低了 COX-2/PGE2 和 iNOS/NO 水平，从而降低了信号转导和转录激活因子（STAT）-1 的磷酸化。CSL 还增强了 Nrf2 的核易位，提高了 Nrf2 与抗氧化反应元件（AREs）之间的结合活性，并降低了 LPS 处理的 HUVEC 中 IL-1β 的表达。我们发现，通过 RNAi 抑制 HO-1，CSL 可以恢复对 iNOS/NO 合成的抑制作用。在动物模型中，CSL 显著降低了肺生物结构中的 iNOS 表达和支气管肺泡灌洗液中的 TNF-α 水平。这些发现表明，CSL 通过抑制 NF-κB 表达和 p-STAT-1 来控制 iNOS，从而具有抗炎特性。因此，CSL 可能有潜力成为开发治疗病理性炎症的新临床物质的候选物。
