Ahmad Tarek B, Rudd David, Benkendorff Kirsten, Mahdi Layla K, Pratt Kaylah-Ann, Dooley Leanne, Wei Chuanyu, Kotiw Michael
Marine Ecology Research Centre, School of Environment, Science and Engineering, Southern Cross University, Lismore, NSW, Australia.
Centre for Health Sciences Research, University of Southern Queensland, Toowoomba, QLD, Australia.
PLoS One. 2017 Oct 26;12(10):e0186904. doi: 10.1371/journal.pone.0186904. eCollection 2017.
New drug leads for the treatment of inflammation are urgently needed. Marine molluscs are widely used as traditional medicines for the treatment of inflammation. Here we report the positive effects of a hypobranchial gland (HBG) extract and the dominant bioactive compound 6-bromoisatin from the Muricidae mollusc Dicathais orbita, for reducing lipopolysaccharide (LPS) induced acute lung inflammation in a mouse model. Both 6-bromoisatin and the HBG extract suppressed the inflammatory response in mice that were pre-treated by oral gavage at 48, 24 and 1 h prior to LPS infusion. The inflammatory antagonists were tested at concentrations of 0.5 mg/g and 0.1 mg/g HBG extract and 0.1 mg/g and 0.05 mg/g 6-bromoisatin in carrier oil and all treatments reduced inflammation as indicated by a significant suppression of inflammatory markers present in bronchoalveolar lavage fluid (BALF), in comparison to LPS induced positive control mice administered the carrier oil alone (p < 0.0001). Tumour necrosis factor-alpha (TNFα) and interleukin-1 beta (IL-1β) levels, in addition to total protein concentration were all significantly reduced in BALF from mice treated with the extract or 6-bromoisatin. Furthermore, all treatment groups showed significant reductions in neutrophil sequestration and preservation of the lung tissue architecture compared to the positive control (p < 0.0001). The combined results from this study and our previous in vitro studies indicate that 6-bromoisatin in the HGB extracts inhibit the activation of inflammatory signalling pathway. The results from this study further confirm that the HBG extract from Muricidae molluscs and 6-bromoisatin are bioavailable and effective in vivo, thus have potential for development as natural therapeutic agents for inflammation.
目前迫切需要治疗炎症的新药线索。海洋软体动物被广泛用作治疗炎症的传统药物。在此，我们报告了来自骨螺科软体动物Dicathais orbita的鳃下腺（HBG）提取物及其主要生物活性化合物6-溴异吲哚酮，在小鼠模型中对减轻脂多糖（LPS）诱导的急性肺部炎症的积极作用。6-溴异吲哚酮和HBG提取物均抑制了在LPS注入前48、24和1小时经口灌胃预处理的小鼠的炎症反应。在载体油中以0.5 mg/g和0.1 mg/g的HBG提取物以及0.1 mg/g和0.05 mg/g的6-溴异吲哚酮浓度测试了炎症拮抗剂，与仅给予载体油的LPS诱导的阳性对照小鼠相比，所有处理均减轻了炎症，这表现为支气管肺泡灌洗液（BALF）中存在的炎症标志物受到显著抑制（p < 0.0001）。用提取物或6-溴异吲哚酮处理的小鼠的BALF中，肿瘤坏死因子-α（TNFα）和白细胞介素-1β（IL-1β）水平以及总蛋白浓度均显著降低。此外，与阳性对照相比，所有处理组的中性粒细胞隔离均显著减少，肺组织结构得以保留（p < 0.0001）。这项研究与我们之前的体外研究的综合结果表明，HGB提取物中的6-溴异吲哚酮可抑制炎症信号通路的激活。这项研究的结果进一步证实，骨螺科软体动物的HBG提取物和6-溴异吲哚酮在体内具有生物利用度且有效，因此有潜力开发成为治疗炎症的天然治疗剂。
