Somma Fabio, Romano Benedetta, Maresca Daniela Claudia, Maisto Maria, Tenore Giancarlo, Ianaro Angela, Ercolano Giuseppe
Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples, Italy.
Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples, Italy.
Biomed Pharmacother. 2025 Jan;182:117784. doi: 10.1016/j.biopha.2024.117784. Epub 2024 Dec 23.
Mast cell-mediated reactions promote various allergic disease, including anaphylaxis, allergic rhinitis, asthma, and atopic dermatitis. Different data demonstrated an intricate relationship between the use of antihistaminic drugs, the onset of side effects, and the development of resistance, underscoring the importance to find novel therapeutic approaches to treat allergic diseases. Olive leaf extract (OLE), is a by-product of the olive tree rich in bioactive compounds, known for its numerous therapeutic properties, including antioxidant, anti-tumoral and antidiabetic effects. In this study, we investigated the effect of OLE on the mast-cell-mediated allergic inflammation using human mast cells HMC-1.2. OLE reduced histamine and β-Hexosaminidase release from HMC cells activated by phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI) through modulation of calcium signal. Moreover, OLE decreased the PMACI-stimulated gene expression of proinflammatory cytokines such as tumor necrosis factor-a (TNF-α), interleukin-8 (IL-8) and interleukin-6 (IL-6) in human mast cells. This result was confirmed by multiplex assay in which the pre-treatment with OLE reduced the effective secretion of TNF-α, IL-6 and IL-8. These effects were correlated to ROS reduction and modulation of both mitochondrial mass and membrane potential. Finally, the inhibitory effect of OLE was nuclear factor (NF)-kB dependent as demonstrated by both activity assay and Western Blot analysis. Taken together, our results demonstrated that OLE inhibits mast-cell-derived allergic inflammation modulating mast cells degranulation, proinflammatory cytokines release and NF-kB activation. Therefore, OLE could represent a novel potential therapeutic approach for the treatment of mast cell-associated disorders.
肥大细胞介导的反应会引发各种过敏性疾病，包括过敏反应、过敏性鼻炎、哮喘和特应性皮炎。不同的数据表明，抗组胺药物的使用、副作用的发生以及耐药性的发展之间存在复杂的关系，这凸显了寻找治疗过敏性疾病新治疗方法的重要性。橄榄叶提取物（OLE）是橄榄树的一种副产品，富含生物活性化合物，以其多种治疗特性而闻名，包括抗氧化、抗肿瘤和抗糖尿病作用。在本研究中，我们使用人肥大细胞HMC-1.2研究了OLE对肥大细胞介导的过敏性炎症的影响。OLE通过调节钙信号，减少了由佛波醇12-肉豆蔻酸酯13-乙酸酯和钙离子载体A23187（PMACI）激活的HMC细胞中组胺和β-己糖胺酶的释放。此外，OLE降低了人肥大细胞中PMACI刺激的促炎细胞因子如肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）和白细胞介素-6（IL-6）的基因表达。多重分析证实了这一结果，其中用OLE预处理减少了TNF-α、IL-6和IL-8的有效分泌。这些作用与活性氧的减少以及线粒体质量和膜电位的调节相关。最后，活性分析和蛋白质免疫印迹分析均表明，OLE的抑制作用依赖于核因子（NF）-κB。综上所述，我们的结果表明，OLE通过调节肥大细胞脱颗粒、促炎细胞因子释放和NF-κB激活来抑制肥大细胞衍生的过敏性炎症。因此，OLE可能是治疗肥大细胞相关疾病的一种新的潜在治疗方法。
