Kondeva-Burdina Magdalena, Panayotova Dona, Nedialkov Paraskev T, Kokanova-Nedialkova Zlatina
Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
Pharmacognosy Department, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
Molecules. 2025 Feb 26;30(5):1061. doi: 10.3390/molecules30051061.
The development of more effective treatments for neurodegenerative disorders presents a significant challenge in modern medicine. Currently, scientists are focusing on discovering bioactive compounds from plant sources to prevent and treat neurodegenerative diseases. Fifteen flavonoids and saponins from Asch. and - L. were tested for their inhibitory activity on hMAO-A and hMAO-B. Five compounds (1 μM) exhibit a weak inhibitory effect on hMAO-A and show good inhibitory activity against the hMAO-B enzyme (30-35%), compared to the positive control selegiline (55%). These active compounds were examined on rat brain synaptosomes and mitochondria obtained by multiple differential centrifugations using a Percoll gradient. Their effects were also monitored on rat brain microsomes obtained by double differential centrifugation. The main parameters characterizing the functional-metabolic status of subcellular fractions are synaptosomal viability, GSH level, and MDA production. All tested compounds (50 μM) demonstrated significant neuroprotective and antioxidant activities across models of induced oxidative stress, including 6-OHDA, t-BuOOH, and FeAA-induced lipid peroxidation. The plausible mechanisms of neuroprotection rely on MAO-B inhibition, the scavenging of ROS, stabilizing the cell membrane by reducing MDA production, and neutralizing free radicals by maintaining GSH levels. In addition, we developed and validated a UHPLC-HRMS method for identifying and simultaneously quantificatying flavonoids and saponins in the aerial parts of . Compounds 30-normedicagenic acid- HexA-Hex-TA and medicagenic acid-HexA-Hex-TA were considered new natural compounds.
开发更有效的神经退行性疾病治疗方法是现代医学面临的一项重大挑战。目前，科学家们正致力于从植物来源中发现生物活性化合物，以预防和治疗神经退行性疾病。对来自Asch.和-L.的15种黄酮类化合物和皂苷进行了对人单胺氧化酶-A（hMAO-A）和人单胺氧化酶-B（hMAO-B）的抑制活性测试。与阳性对照司来吉兰（55%）相比，5种化合物（1μM）对hMAO-A表现出微弱的抑制作用，而对hMAO-B酶显示出良好的抑制活性（30-35%）。这些活性化合物在通过使用Percoll梯度的多次差速离心获得的大鼠脑突触体和线粒体上进行了检测。它们对通过双重差速离心获得的大鼠脑微粒体的作用也进行了监测。表征亚细胞组分功能代谢状态的主要参数是突触体活力、谷胱甘肽（GSH）水平和丙二醛（MDA）生成量。所有测试化合物（50μM）在包括6-羟基多巴胺（6-OHDA）、叔丁基过氧化氢（t-BuOOH）和亚铁血红素-氨基酸（FeAA）诱导的脂质过氧化等诱导氧化应激模型中均表现出显著的神经保护和抗氧化活性。神经保护的可能机制依赖于对MAO-B的抑制、对活性氧（ROS）的清除、通过减少MDA生成来稳定细胞膜以及通过维持GSH水平来中和自由基。此外，我们开发并验证了一种超高效液相色谱-高分辨质谱（UHPLC-HRMS）方法，用于鉴定和同时定量[植物名称]地上部分中的黄酮类化合物和皂苷。化合物30-去甲苜蓿酸-己糖醛酸-己糖-塔罗糖酸和苜蓿酸-己糖醛酸-己糖-塔罗糖酸被认为是新的天然化合物。
