Abstract：
The bisindolic alkaloid caulerpin (CAU) is a bioactive compound isolated from green algae of the genus Caulerpa that are highly invasive in the Mediterranean Sea. On the other side, the purine alkaloid caffeine (CAF) is one of the most globally consumed psychoactive substances and a widespread anthropogenic water pollutant. Both compounds display a large panel of biological properties and are well known to accumulate in the tissues of aquatic organisms and, in certain circumstances, co-occur in the human diet. On this premise, the present study aimed to investigate possible synergistic interactions between CAU and CAF by using the bivalve Mytilus galloprovincialis as a model organism. Mussels were exposed to CAF via medium while they were fed with food enriched with CAU. After treatments, biochemical analysis confirmed the toxic potential of CAF, with increased AChE activity and lipid peroxidation. Also, histopathological alterations were observed in the gills and digestive tubules. The NMR-based metabolomics analysis detected higher levels of free amino acids under CAF treatments. Conversely, the food administration of CAU did not affect the above toxicological biomarkers. In addition, we did not observe any cumulative effect between CAF and CAU toward increased cellular damage and neurotoxicity. On the other hand, a possible action of CAU in decreasing CAF toxicity could be hypothesized based on our results. This hypothesis is supported by the activity of CAU as an agonist of peroxisome proliferator-activated receptors (PPARs). PPARs mediate xenobiotic detoxification via cytochromes P450, which is involved in CAF metabolism. Overall, the results obtained not only rule out any cumulative adverse effects of CAF and CAU but also encourage further research to evaluate the possible use of CAU, a compound easily obtained through the valorization of biomass from invasive species, as a food additive to improve the clearance of xenobiotics.
摘要：
双吲哚生物碱culerpin（CAU）是一种生物活性化合物，从地中海高度侵入的Caulerpa属绿藻中分离出来。在另一边,嘌呤生物碱咖啡因（CAF）是全球消费最多的精神活性物质之一，也是广泛存在的人为水污染物。这两种化合物都显示出大量的生物学特性，并且众所周知会在水生生物的组织中积累，在某些情况下,在人类饮食中共同出现。在这个前提下,本研究旨在通过使用双壳类菌作为模型生物来研究CAU和CAF之间可能的协同相互作用。贻贝通过培养基暴露于CAF，同时喂食富含CAU的食物。治疗后,生化分析证实了CAF的毒性潜力，与增加的AChE活性和脂质过氧化。此外，在the和消化管中观察到组织病理学改变。基于NMR的代谢组学分析在CAF治疗下检测到较高水平的游离氨基酸。相反，CAU的食物管理不影响上述毒理学生物标志物.此外,我们未观察到CAF和CAU对细胞损伤和神经毒性增加的累积效应.另一方面,根据我们的结果,可以推测CAU可能具有降低CAF毒性的作用.CAU作为过氧化物酶体增殖物激活受体（PPAR）激动剂的活性支持了这一假设。PPAR通过参与CAF代谢的细胞色素P450介导异种生物解毒。总的来说,获得的结果不仅排除了CAF和CAU的任何累积不利影响，而且还鼓励进一步研究以评估CAU的可能使用，一种很容易通过入侵物种的生物量增值获得的化合物，作为食品添加剂，以提高外源性物质的清除率。
