酪氨酸(GA),地衣次生代谢产物,由于其潜在的生物学效应,在过去几年中引起了更多的关注。直到现在,其在体内的作用尚未得到证实。我们研究的目的是评估GA的基本物理化学和药代动力学特性,与它的生物活性直接相关。通过进行重复的UV-VIS光谱测量来评估GA在各种pH下的稳定性。使用Ultra-PerformanceLC/MS进行大鼠肝微粒体的微粒体稳定性。使用同步荧光光谱评估与人血清白蛋白(HSA)的结合,分子对接分析用于揭示GA与HSA的结合位点。在体内实验中,24Sprague-Dawley大鼠(Velaz,Ulnetice,捷克共和国)被使用。动物的划分如下。第一组(n=6)包括健康雄性作为对照的完整大鼠(‰INT),第二组(n=6)包括健康女性作为对照(█INT)。第3和第4组(‰GA/n=6和‰GA/n=6)由每天口服乙醇水溶液中的GA(10mg/kg体重)的动物组成,为期一个月。我们发现GA在各种pH和温度条件下保持稳定。它与人血清白蛋白结合,结合常数为1.788×106dm3mol-1,通过这种机制到达靶组织。在体内,GA不影响体重增长,食物,或实验期间的液体摄入量。没有观察到肝毒性。然而,GA增加了行为测试中的饲养频率(p<0.01)和高架迷宫中的中心交叉(分别为p<0.01和p<0.001)。此外,在开放臂中花费的时间延长(分别为p<0.01和p<0.001)。值得注意的是,GA能够穿过血脑屏障,表明它有能力渗透到大脑中并刺激海马的门和颗粒下区域的神经发生。这些观察结果强调了GA在影响脑功能和神经发生中的潜在作用。
Gyrophoric acid (GA), a lichen secondary metabolite, has attracted more attention during the last years because of its potential biological effects. Until now, its effect in vivo has not yet been demonstrated. The aim of our study was to evaluate the basic physicochemical and pharmacokinetic properties of GA, which are directly associated with its biological activities. The stability of the GA in various pH was assessed by conducting repeated UV-VIS spectral measurements. Microsomal stability in rat liver microsomes was performed using Ultra-Performance LC/MS. Binding to human serum albumin (HSA) was assessed using synchronous fluorescence spectra, and molecular docking analysis was used to reveal the binding site of GA to HSA. In the in vivo experiment, 24 Sprague-Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided as follows. The first group (n = 6) included healthy males as control intact rats (♂INT), and the second group (n = 6) included healthy females as controls (♀INT). Groups three and four (♂GA/n = 6 and ♀GA/n = 6) consisted of animals with daily administered GA (10 mg/kg body weight) in an ethanol-water solution per os for a one-month period. We found that GA remained stable under various pH and temperature conditions. It bonded to human serum albumin with the binding constant 1.788 × 106 dm3mol-1 to reach the target tissue via this mechanism. In vivo, GA did not influence body mass gain, food, or fluid intake during the experiment. No liver toxicity was observed. However, GA increased the rearing frequency in behavioral tests (p < 0.01) and center crossings in the elevated plus-maze (p < 0.01 and p < 0.001, respectively). In addition, the time spent in the open arm was prolonged (p < 0.01 and p < 0.001, respectively). Notably, GA was able to pass through the blood-brain barrier, indicating its ability to permeate into the brain and to stimulate neurogenesis in the hilus and subgranular zone of the hippocampus. These observations highlight the potential role of GA in influencing brain function and neurogenesis.