Chemical Neuroscience Group, Faculty of Medicine, Centre for Molecular Medicine Norway, University of Oslo, Gaustadalléen 21, 0349 Oslo, Norway.
Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego Str. 8b, 20-090 Lublin, Poland.
Cells. 2020 May 16;9(5):1233. doi: 10.3390/cells9051233.
Palmatine (PALM) and berberine (BERB) are widely identified isoquinoline alkaloids among the representatives of the Berberidaceae botanical family. The antiseizure activity of BERB was shown previously in experimental epilepsy models. We assessed the effect of PALM in a pentylenetetrazole (PTZ)-induced seizure assay in zebrafish, with BERB as an active reference compound. Both alkaloids were isolated from the methanolic root extract of by counter-current chromatography, and their ability to cross the blood-brain barrier was determined via quantitative structure-activity relationship assay. PALM exerted antiseizure activity, as confirmed by electroencephalographic analysis, and decreased and levels in PTZ-treated larvae. In a behavioral assay, PALM dose-dependently decreased PTZ-induced hyperlocomotion. The combination of PALM and BERB in ED doses revealed hyperadditive activity towards PTZ-induced hyperlocomotion. Notably, we have indicated that both alkaloids may exert their anticonvulsant activity through different mechanisms of action. Additionally, the combination of both alkaloids in a 1:2.17 ratio (PALM: BERB) mimicked the activity of the pure extract, which indicates that these two active compounds are responsible for its anticonvulsive activity. In conclusion, our study reveals for the first time the anticonvulsant activity of PALM and suggests the combination of PALM and BERB may have higher therapeutic value than separate usage of these compounds.
黄连碱 (PALM) 和小檗碱 (BERB) 是小檗科植物中广泛存在的异喹啉生物碱。BERB 的抗惊厥活性先前已在实验性癫痫模型中得到证实。我们在斑马鱼的戊四氮 (PTZ) 诱导的惊厥试验中评估了 PALM 的作用，以 BERB 作为活性参考化合物。两种生物碱均通过逆流色谱法从根甲醇提取物中分离得到，并通过定量构效关系测定法测定其穿过血脑屏障的能力。PALM 通过脑电图分析证实具有抗惊厥活性，并降低了 PTZ 处理幼虫中的 和 水平。在行为测定中，PALM 剂量依赖性地降低了 PTZ 诱导的过度运动。PALM 和 BERB 在 ED 剂量下的组合对 PTZ 诱导的过度运动显示出超相加活性。值得注意的是，我们已经表明，这两种生物碱可能通过不同的作用机制发挥其抗惊厥作用。此外，以 1:2.17 的比例 (PALM:BERB) 组合两种生物碱模拟了纯提取物的活性，这表明这两种活性化合物是其抗惊厥活性的原因。总之，我们的研究首次揭示了 PALM 的抗惊厥活性，并表明 PALM 和 BERB 的组合可能比单独使用这些化合物具有更高的治疗价值。
