Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland.
Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland.
Psychopharmacology (Berl). 2021 Nov;238(11):3167-3181. doi: 10.1007/s00213-021-05933-5. Epub 2021 Aug 1.
Pterostilbene is the 3,5-dimethoxy derivative of resveratrol with numerous beneficial effects including neuroprotective properties. Experimental studies revealed its anticonvulsant action in the acute seizure tests.
The purpose of the present study was to evaluate the effect of pterostilbene in the pentetrazol (PTZ)-induced kindling model of epilepsy in mice as well as to assess some possible mechanisms of its anticonvulsant action in this model.
Mice were repeatedly treated with pterostilbene (50-200 mg/kg) and its effect on the development of seizure activity in the PTZ kindling was estimated. Influence of pterostilbene on the locomotor activity and anxiety- and depression-like behavior in the PTZ-kindled mice was also assessed. To understand the possible mechanisms of anticonvulsant activity of pterostilbene, γ-aminobutyric acid (GABA) and glutamate concentrations in the prefrontal cortex and hippocampus of the PTZ-kindled mice were measured using LC-MS/MS method. Moreover, mRNA expression of BDNF, TNF-α, IL-1β, IL-6, GABRA1A, and GRIN2B was determined by RT-qPCR technique.
We found that pterostilbene at a dose of 200 mg/kg considerably reduced seizure activity but did not influence the locomotor activity and depression- and anxiety-like behavior in the PTZ-kindled mice. In the prefrontal cortex and hippocampus, pterostilbene reversed the kindling-induced decrease of GABA concentration. Neither in the prefrontal cortex nor hippocampus pterostilbene affected mRNA expression of IL-1β, IL-6, GABRA1A, and GRIN2B augmented by PTZ kindling. Pterostilbene at a dose of 100 mg/kg significantly decreased BDNF and TNF-α mRNA expression in the hippocampus of the PTZ-kindled mice.
Although further studies are necessary to understand the mechanism of anticonvulsant properties of pterostilbene, our findings suggest that it might be considered a candidate for a new antiseizure drug.
白藜芦醇的 3,5-二甲氧基衍生物是紫檀芪，具有多种有益作用，包括神经保护作用。实验研究表明其具有抗惊厥作用。
本研究旨在评估紫檀芪对小鼠戊四氮（PTZ）点燃模型癫痫的影响，并评估其在该模型中抗惊厥作用的一些可能机制。
小鼠反复给予紫檀芪（50-200mg/kg），并评估其对 PTZ 点燃过程中癫痫发作活动的影响。还评估了紫檀芪对 PTZ 点燃小鼠运动活动和焦虑-抑郁样行为的影响。为了了解紫檀芪抗惊厥作用的可能机制，使用 LC-MS/MS 方法测量了 PTZ 点燃小鼠前额叶皮层和海马中的γ-氨基丁酸（GABA）和谷氨酸浓度。此外，通过 RT-qPCR 技术测定 BDNF、TNF-α、IL-1β、IL-6、GABRA1A 和 GRIN2B 的 mRNA 表达。
我们发现，紫檀芪在 200mg/kg 剂量下可显著减少癫痫发作活动，但不影响 PTZ 点燃小鼠的运动活动和抑郁-焦虑样行为。在前额叶皮层和海马中，紫檀芪逆转了点燃引起的 GABA 浓度降低。PTZ 点燃引起的 IL-1β、IL-6、GABRA1A 和 GRIN2B 的 mRNA 表达增加，紫檀芪在前额叶皮层和海马中均未产生影响。紫檀芪 100mg/kg 剂量可显著降低 PTZ 点燃小鼠海马中的 BDNF 和 TNF-α mRNA 表达。
尽管还需要进一步研究以了解紫檀芪抗惊厥特性的机制，但我们的研究结果表明，它可能被认为是一种新的抗癫痫药物候选物。
