Salviplenoid A from Salvia plebeia attenuates acute lung inflammation via modulating NF-κB and Nrf2 signaling pathways
Salviplenoid A from Salvia plebeia attenuates acute lung inflammation via modulating NF-κB and Nrf2 signaling pathways
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DOI：
10.1002/ptr.6922
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发表时间：
2020-10-23
影响因子：
7.2
通讯作者：
Tang, Gui-Hua
中科院分区：
文献类型：
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作者：
Huang, Jia-Luo;Fan, Run-Zhu;Tang, Gui-Hua
急性肺损伤（ALI）涉及一系列炎症病理过程，并导致高发病率。鼠尾草酸A（SA）是一种从传统抗炎草药荔枝草中提取的新型倍半萜类化合物。在我们之前的研究中，SA在RAW264.7细胞中表现出抗炎活性。然而，SA在人体细胞和体内的广泛作用及其活性机制尚不清楚。因此，在本研究中，我们试图了解其在体外和体内的作用并探究其机制。SA被证明可抑制包括肺上皮细胞和内皮细胞在内的多种人类细胞类型中促炎细胞因子的诱导。它还能抑制单核细胞黏附。此外，在脂多糖诱导的小鼠模型中，SA可有效减轻急性肺部炎症，表现为促炎介质的下调、多形核中性粒细胞浸润的抑制以及肺泡充血和黏液分泌等相关症状的缓解。进一步评估证实，SA通过抑制IκB -α磷酸化来调节NF -κB通路。并且它通过激活Nrf2/HO -1表达并促进Nrf2核转位显著介导Nrf2/HO -1通路。因此，SA可通过抑制NF -κB和激活Nrf2来减轻急性肺部炎症，这为SA在临床上的潜在应用提供了理论依据。
Acute lung injury (ALI) involves series of inflammatory pathologies and cause high morbidity. Salviplenoid A (SA) was a new sesquiterpenoid from the traditional inflammatory herb Salvia plebeia. In our previous study, SA exhibited antiinflammatory activity in RAW264.7 cells. However, the extensive effects of SA in human cells and in vivo and the active mechanisms are unclear. Thus, in this study, we sought to access its effects in vitro and in vivo and to investigate its mechanisms. SA was proved to inhibit the induction of proinflammatory cytokines in human cell types, including pulmonary epithelial cells and endothetial cells. It also depressed monocyte adhesion. Moreover, SA potently attenuated the acute lung inflammation in the LPS-induced mouse model shown by down-regulation of proinflammatory mediators, inhibition of polymorphonuclear neutrophil infiltration, and alleviation of related symptoms like alveolar congestion and mucus secretion. Further evaluation confirmed that SA regulated NF-kappa B pathway by inhibiting the I kappa B-alpha phosphorylation. And it markedly mediated Nrf2/HO-1 pathway by activating the Nrf2/HO-1 expression and promoting Nrf2 nuclear translocation. Therefore, SA could attenuate acute lung inflammation via suppressing NF-kappa B and activating Nrf2, which provide a theoretical basis for the potential application of SA in clinic.