School of Korean Medicine, Pusan National University, Yangsan, 50612, Republic of Korea.
Department ofs Biomedical Laboratory Science, Division of Health Sciences, Dongseo University, Busan, 47011, Republic of Korea.
BMC Complement Med Ther. 2020 Feb 7;20(1):40. doi: 10.1186/s12906-020-2828-6.
Guettarda speciosa is mainly found in tropical areas in Asia. Although G. speciosa is traditionally used to treat some of the inflammatory disorders, the experimental evidence supporting the anti-inflammatory effect of G. speciosa is limited. Here, we sought to obtain evidence that G. speciosa has anti-inflammatory activity using an acute lung injury (ALI) mouse model and to explore possible underlying mechanisms for the activity.
The methanol extract of G. speciosa Linn. (MGS) was fingerprinted by HPLC. Cytotoxicity was determined by MTT and flow cytometer. As for an ALI mouse model, C57BL/6 mice received an intratracheal (i.t.) injection of lipopolysaccharide (LPS). The effects of MGS on lung inflammation in the ALI mice were assessed by differential cell counting and FACS of inflammatory cells and hematoxylin and eosin staining of lung tissue. Proteins were analyzed by immunoprecipitation and immunoblotting, and gene expression was by real-time qPCR. Neutrophil elastase activity was measured by ELISA.
MGS did not cause metabolic disarray or produce reactive oxygen species that could induce cytotoxicity. Similar to ALI patients, C57BL/6 mice that received an i.t. LPS developed a high level of neutrophils, increased pro-inflammatory cytokines, and inflicted tissue damage in the lung, which was suppressed by i.t. MGS administered at 2 h after LPS. Mechanistically, MGS activated Nrf2, which was related to MGS interrupting the ubiquitin-dependent degradation of Nrf2. MGS suppressed the nuclear localization of NF-κB induced by LPS, suggesting the inhibition of NF-κB activity. Furthermore, MGS inhibited the enzymatic activity of neutrophil elastase.
MGS could suppress lung inflammation in an ALI mouse model, the effect of which could be attributed to multiple mechanisms, including the activation of Nrf2 and the suppression of NF-κB and neutrophil elastase enzymatic activity by MGS.
美丽异木棉主要分布在亚洲的热带地区。尽管美丽异木棉传统上被用于治疗一些炎症性疾病，但支持其抗炎作用的实验证据有限。在这里，我们试图使用急性肺损伤（ALI）小鼠模型获得美丽异木棉具有抗炎活性的证据，并探索其活性的可能潜在机制。
通过高效液相色谱法对美丽异木棉林奈甲醇提取物（MGS）进行指纹图谱分析。通过 MTT 和流式细胞术测定细胞毒性。对于 ALI 小鼠模型，C57BL/6 小鼠接受气管内（i.t.）注射脂多糖（LPS）。通过对炎症细胞的差异细胞计数和流式细胞术以及肺组织的苏木精和伊红染色，评估 MGS 对 ALI 小鼠肺部炎症的影响。通过免疫沉淀和免疫印迹分析蛋白质，通过实时 qPCR 分析基因表达。通过 ELISA 测定中性粒细胞弹性蛋白酶活性。
MGS 不会引起代谢紊乱或产生诱导细胞毒性的活性氧。与 ALI 患者相似，接受气管内 LPS 注射的 C57BL/6 小鼠产生高水平的中性粒细胞、增加的促炎细胞因子，并在肺中造成组织损伤，而气管内给予 MGS 可抑制这种损伤，MGS 在 LPS 后 2 小时给予。从机制上讲，MGS 激活了 Nrf2，这与 MGS 中断 Nrf2 的泛素依赖性降解有关。MGS 抑制了 LPS 诱导的 NF-κB 的核定位，表明抑制了 NF-κB 活性。此外，MGS 抑制了中性粒细胞弹性蛋白酶的酶活性。
MGS 可抑制 ALI 小鼠模型中的肺炎症，其作用可能归因于多种机制，包括 MGS 激活 Nrf2 以及抑制 NF-κB 和中性粒细胞弹性蛋白酶的酶活性。
