Matacchione Giulia, Borgonetti Vittoria, Ramini Deborah, Silvestrini Andrea, Ojetti Marta, Galeotti Nicoletta, Olivieri Fabiola
Department of Clinical and Molecular Sciences, Università Politecnica Delle Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
Biology (Basel). 2023 Mar 12;12(3):438. doi: 10.3390/biology12030438.
Aging is related to a low-grade and sterile inflammation called inflammaging, recognized as the main risk factor for age-related disease (ARD) development. Inflammaging is fostered by the repeated activation of immune cells, as well as by the accumulation of senescent cells. Recently, a number of natural compounds have gained attention to be tested as anti-aging therapies, based on their anti-inflammatory activity and/or ability to reduce the pro-inflammatory secretome of senescent cells (senomorphyc activity). Here, we investigated the anti-inflammatory and senomorphic properties of an Asian-native Roscoe extract (ZOE), commonly consumed as a food spice and herbal medicine. We employed two models of primary endothelial cells (HUVECs), such as the replicative-senescence and LPS-induced response, to investigate the anti-inflammatory/senomorphic effect of ZOE, and one cellular model of neuroinflammation, i.e., immortalized murine microglial cells (BV2). First, we found that the ZOE treatment induced the inhibition of NF-kB activation in BV2 cells. Among the constituents of ZOE, we showed that the terpenoid-enriched fraction (ZTE) was the component able to counteract the phosphorylation of NF-kB(p65), while 6-gingerol (GIN) and 6-shogaol (SHO) did not produce any significant effect. Further, we observed that the treatment with 10 µg/mL of ZOE exerted anti-inflammatory activity on LPS-stimulated young (y)HUVEC and senomorphyc activity on replicative senescent (s)HUVEC, significantly reducing the expression levels of IL-1β, TNF -α, IL-8, MCP-1, and ICAM-1. Moreover, the ZTE treatment was able to significantly reduce the IL-8 levels secreted in the medium of both LPS-stimulated yHUVEC and sHUVEC. Overall, our data suggest a potential protective role of ZOE on neuroinflammation and endothelial inflammation/activation, thus suggesting its potential relevance in delaying/postponing ARD development and progression, characterized by endothelial dysfunction.
衰老与一种称为炎症衰老的低度无菌性炎症有关，炎症衰老被认为是与年龄相关疾病（ARD）发展的主要危险因素。免疫细胞的反复激活以及衰老细胞的积累会促进炎症衰老。最近，一些天然化合物因其抗炎活性和/或降低衰老细胞促炎分泌组的能力（衰老形态调节活性）而受到关注，被作为抗衰老疗法进行测试。在此，我们研究了一种原产于亚洲的迷迭香叶提取物（ZOE）的抗炎和衰老形态调节特性，ZOE通常作为食品香料和草药食用。我们采用了两种原代内皮细胞（HUVEC）模型，即复制性衰老模型和LPS诱导反应模型，来研究ZOE的抗炎/衰老形态调节作用，以及一种神经炎症细胞模型，即永生化小鼠小胶质细胞（BV2）。首先，我们发现ZOE处理可诱导BV2细胞中NF-κB激活的抑制。在ZOE的成分中，我们发现富含萜类化合物的部分（ZTE）是能够抵消NF-κB（p65）磷酸化的成分，而6-姜酚（GIN）和6-姜烯酚（SHO）没有产生任何显著影响。此外，我们观察到用10μg/mL的ZOE处理对LPS刺激的年轻（y）HUVEC具有抗炎活性，对复制性衰老（s）HUVEC具有衰老形态调节活性，显著降低了IL-1β、TNF-α、IL-8、MCP-1和ICAM-1的表达水平。此外，ZTE处理能够显著降低LPS刺激的yHUVEC和sHUVEC培养基中分泌的IL-8水平。总体而言，我们的数据表明ZOE对神经炎症和内皮炎症/激活具有潜在的保护作用，从而表明其在延缓/推迟以内皮功能障碍为特征的ARD发展和进展方面的潜在相关性。
