Radulović Niko S, Mladenović Marko Z, Randjelovic Pavle J, Stojanović Nikola M, Dekić Milan S, Blagojević Polina D
Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.
Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.
Food Chem Toxicol. 2015 Jun;80:114-129. doi: 10.1016/j.fct.2015.03.001. Epub 2015 Mar 9.
Herein we report on the comprehensive chemical analysis of the essential oils obtained from above- and underground parts of a previously unreported chemotype of Achillea falcata L. (Asteraceae) and, for the first time, on the biological/toxicological profile of its dominant/newly discovered volatile metabolites. Detailed spectral analyses, in combination with chemical synthesis and theoretical study, of selected constituents, enabled the identification of trans-sabinol and its esters - the formate, tiglate (new compounds), acetate, butanoate, isobutanoate, 2-methylbutanoate and 3-methylbutanoate - in both aerial and underground parts of A. falcata. Evaluation of acute toxicity in Artemia salina model, in vitro and in silico (molecular docking) evaluation of acetylcholinesterase inhibitory activity and in vivo (mice) evaluation of antinociceptive activity (hot plate, tail immersion and acetylcholine-induced abdominal writhing tests) of trans-sabinol and its esters suggested that they may interact with different targets in crustacean/mammalian organisms. Alongside moderate acute toxicity (LD50 (48 h) = 0.03-0.26 mmol/L), the tested compounds exert influence on both the peripheral and central nervous systems (in the hot plate test, trans-sabinyl tiglate, at 50 mg/kg, produced a 140% baseline increase 15 min after the treatment) and to moderately inhibit acetylcholinesterase (at the concentration of 20 µg/mL, these compounds caused a reduction of acetylcholinesterase activity up to 40%).
在此，我们报告了对从未报道过的化学型镰叶蓍（菊科）地上和地下部分所获精油的综合化学分析，并首次报告了其主要/新发现挥发性代谢物的生物学/毒理学特征。通过对选定成分进行详细的光谱分析，并结合化学合成和理论研究，在镰叶蓍的地上和地下部分均鉴定出反式桧醇及其酯类——甲酸酯、惕各酸酯（新化合物）、乙酸酯、丁酸酯、异丁酸酯、2-甲基丁酸酯和3-甲基丁酸酯。在卤虫模型中评估急性毒性，对反式桧醇及其酯类进行体外和计算机模拟（分子对接）乙酰胆碱酯酶抑制活性评估，以及在体内（小鼠）评估其抗伤害感受活性（热板法、尾浸法和乙酰胆碱诱导的扭体试验），结果表明它们可能与甲壳类/哺乳动物生物体中的不同靶点相互作用。除了具有中等急性毒性（LD50（48小时）=0.03 - 0.26 mmol/L）外，受试化合物对外周和中枢神经系统均有影响（在热板试验中，50 mg/kg的反式桧醇惕各酸酯在给药15分钟后使基线增加了140%），并能适度抑制乙酰胆碱酯酶（在20 μg/mL的浓度下，这些化合物使乙酰胆碱酯酶活性降低高达40%）。
