Jiang Kangfeng, Zhang Tao, Yin Nannan, Ma Xiaofei, Zhao Gan, Wu Haichong, Qiu Changwei, Deng Ganzhen
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Oncotarget. 2017 Aug 16;8(41):71038-71053. doi: 10.18632/oncotarget.20298. eCollection 2017 Sep 19.
Geraniol (GOH), a special type of acyclic monoterpene alcohol, has been widely used to treat many diseases associated with inflammation and apoptosis. Acute lung injury (ALI) is a common clinical disease in humans characterized by pulmonary inflammation and apoptosis. In the present study, we investigated the protective effects of GOH in a mouse model of ALI induced by the intranasal administration of lipopolysaccharide (LPS) and elucidated the underlying molecular mechanisms in RAW 264.7 cells. , GOH treatment markedly ameliorated pathological injury and pulmonary cell apoptosis and reduced the wet/dry (W/D) weight ratio of lungs, myeloperoxidase (MPO) activity and the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). , the levels of pro-inflammatory cytokines, iNOS and COX-2 were significantly increased in LPS-stimulated RAW 264.7 cells, an effect that was decreased by GOH treatment. Moreover, GOH treatment dramatically reduced the expression of Toll-like receptor 4 (TLR4) and then prevented the nuclear factor-κB (NF-κB) activation. GOH treatment also promoted anti-apoptotic Bcl-2 expression and inhibited pro-apoptotic Bax and Caspase-3 expression. Furthermore, knockdown of TLR4 expression exerted a similar effect and inhibited the phosphorylation of p65, as well as the Bax and Caspase-3 expression. Taken together, these results suggest that GOH treatment alleviates LPS-induced ALI via inhibiting pulmonary inflammation and apoptosis, a finding that might be associated with the inhibition of TLR4-mediated NF-κB and Bcl-2/Bax signalling pathways.
香叶醇（GOH）是一种特殊的无环单萜醇，已被广泛用于治疗许多与炎症和细胞凋亡相关的疾病。急性肺损伤（ALI）是人类常见的临床疾病，其特征为肺部炎症和细胞凋亡。在本研究中，我们研究了GOH在经鼻内给予脂多糖（LPS）诱导的ALI小鼠模型中的保护作用，并阐明了RAW 264.7细胞中的潜在分子机制。GOH治疗显著改善了病理损伤和肺细胞凋亡，并降低了肺的湿/干（W/D）重量比、髓过氧化物酶（MPO）活性以及促炎细胞因子（IL-1β、IL-6和TNF-α）的产生。在LPS刺激的RAW 264.7细胞中，促炎细胞因子、诱导型一氧化氮合酶（iNOS）及环氧化酶-2（COX-2）的水平显著升高，而GOH治疗可降低这种作用。此外，GOH治疗显著降低了Toll样受体4（TLR4）的表达，进而阻止了核因子-κB（NF-κB）的激活。GOH治疗还促进了抗凋亡蛋白Bcl-2的表达，并抑制了促凋亡蛋白Bax和半胱天冬酶-（Caspase-3）的表达。此外，敲低TLR4表达也产生了类似的效果，抑制了p65的磷酸化以及Bax和Caspase-3的表达。综上所述，这些结果表明，GOH治疗通过抑制肺部炎症和细胞凋亡来减轻LPS诱导的ALI，这一发现可能与抑制TLR4介导的NF-κB和Bcl-2/Bax信号通路有关。
