BACKGROUND Epilepsy is a chronic neurological disorder affecting more than 50 million people worldwide, of whom 80% live in low- and middle-income countries. Due to the limited availability of antiseizure drugs (ASDs) in these countries, medicinal plants are the first-line treatment for most epilepsy patients. In Cameroon, a decoction of Cyperus articulatus L. rhizomes is traditionally used to treat epilepsy. PURPOSE The aim of this study was to identify and isolate the active compounds responsible for the antiseizure activity of C. articulatus in order to confirm both its traditional medicinal usage and previous in vivo studies on extracts of this plant in mouse epilepsy models. METHODS The dried rhizomes of C. articulatus were extracted with solvents of increasing polaritie (hexane, dichloromethane, methanol and water). A traditional decoction and an essential oil were also prepared. These extracts were evaluated for antiseizure activity using a larval zebrafish seizure model with seizures induced by the GABAA antagonist pentylenetetrazole (PTZ). The hexane extract demonstrated the highest antiseizure activity and was therefore selected for bioassay-guided fractionation. The isolated bioactive compounds were characterized by classical spectroscopic methods. Since they were found to be volatile, they were quantified by GC-FID. In addition, the absorption of the active compounds through the gastrointestinal tract and the blood-brain barrier was evaluated using a hexadecane and a blood-brain barrier parallel artificial membrane permeability assays (HDM-PAMPA and PAMPA-BBB). RESULTS The hexane extract of C. articulatus exhibited the highest antiseizure activity with a reduction of 93% of PTZ-induced seizures, and was therefore subjected to bioassay-guided fractionation in order to isolate the active principles. Four sesquiterpenoids were identified as cyperotundone (1), mustakone (2), 1,2-dehydro-α-cyperone (3) and sesquichamaenol (4) and exhibited significant antiseizure activity. These volatile compounds were quantified by GC in the hexane extract, the essential oil and the simulated traditional decoction. In addition, the constituents of the hexane extract including compounds 1 and 2 were found to cross the gastrointestinal barrier and the major compound 2 crossed the blood-brain barrier as well. CONCLUSION These results highlight the antiseizure activity of various sesquiterpene compounds from a hexane extract of C. articulatus dried rhizomes and support its use as a traditional treatment for epilepsy.

中文翻译：

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斑马鱼生物测定指导的喀麦隆药用植物香附子抗癫痫化合物的分离。

背景技术癫痫病是一种慢性神经系统疾病，影响全世界超过5000万人，其中80％生活在低收入和中等收入国家。由于这些国家抗癫痫药（ASD）的供应有限，药用植物是大多数癫痫患者的一线治疗方法。在喀麦隆，传统上使用香附子水煎剂来治疗癫痫。目的这项研究的目的是鉴定和分离负责关节小球藻抗癫痫活性的活性化合物，以确认其传统的药用用途以及先前在小鼠癫痫模型中对该植物提取物的体内研究。方法用极性增加的溶剂（己烷，二氯甲烷，甲醇和水）提取干燥的C. articulatus根茎。还制备了传统汤剂和精油。使用由GABAA拮抗剂戊四氮（PTZ）诱导的幼虫斑马鱼癫痫发作模型评估这些提取物的抗癫痫活性。己烷提取物显示出最高的抗癫痫活性，因此被选择用于生物测定指导的分离。分离的生物活性化合物通过经典的光谱学方法表征。由于发现它们易挥发，因此通过GC-FID对其进行了定量。另外，使用十六烷和血脑屏障平行人工膜通透性测定法（HDM-PAMPA和PAMPA-BBB）评估了活性化合物通过胃肠道和血脑屏障的吸收。结果C的己烷提取物。关节表现出最高的抗癫痫活性，减少了93％的PTZ诱导的癫痫发作，因此进行了生物测定指导的分级分离以分离出活性成分。四个倍半萜被鉴定为cyperotundone（1），mustakone（2），1,2-dehydro-α-cyperone（3）和倍半茶烯酚（4）并显示出显着的抗癫痫活性。这些挥发性化合物通过GC在己烷提取液，精油和模拟传统汤中定量。另外，发现包括化合物1和2的己烷提取物的成分穿过胃肠道屏障，并且主要化合物2也穿过血脑屏障。结论这些结果突出了C的己烷提取物中各种倍半萜烯化合物的抗癫痫活性。