Department of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410001, Enugu State, Nigeria.
Pharmacol Biochem Behav. 2013 Aug;109:38-43. doi: 10.1016/j.pbb.2013.05.001. Epub 2013 May 8.
The herbal preparations of Annona senegalensis Pers. (Annonaceae) root bark are used in Nigerian ethnomedicine for the treatment of epilepsy and febrile seizures. The scientific evidence for this effect has been reported.
The aim of this study was to identify and characterize the active constituent responsible for the anticonvulsant effect.
Bioactive-guided fractionation of the methanol-methylene chloride root bark extract (MME) of A. senegalensis using pentylenetetrazole (PTZ)-induced seizures in mice, afforded a potent anticonvulsant ethyl-acetate fraction (EF). Further fractionation of the EF yielded eight sub-fractions (F₁-F₈) which were tested for anticonvulsant activity. The sub-fraction F₂ yielded white crystals that were purified to obtain A. senegalensis crystals, AS2. The AS2, which exhibited potent anticonvulsant effects, was characterized by 1D and 2D NMR spectroscopy, mass spectroscopy and X-ray crystallography.
The AS2 was characterized as kaur-16-en-19-oic acid (KA), a diterpenoid. The AS2 indicated an oral LD₅₀ of 3800 mg/kg. The results showed that the MME, EF and AS2 significantly (P<0.05) and dose-dependently delayed the onset of myoclonic spasms and tonic-clonic phases of seizures induced by PTZ and maximal electroshock seizures (MES).
Kaurenoic acid was identified as the anticonvulsant principle in the root bark extract of A. senegalensis. The anticonvulsant effect of the MME, EF and AS2 is most likely being mediated through central inhibitory mechanisms.
安诺那（Annona senegalensis Pers.）根皮的草药制剂在尼日利亚传统医学中用于治疗癫痫和热性惊厥。已经报道了这种作用的科学证据。
本研究的目的是鉴定和表征负责抗惊厥作用的活性成分。
使用戊四氮（PTZ）诱导的小鼠惊厥对安诺那根皮甲醇-二氯甲烷提取物（MME）进行生物活性导向分离，得到一种有效的抗惊厥乙酸乙酯级分（EF）。进一步分离 EF 得到八个亚级分（F₁-F₈），并测试其抗惊厥活性。亚级分 F₂ 得到白色晶体，经纯化得到安诺那晶体 AS2。AS2 表现出强大的抗惊厥作用，通过 1D 和 2D NMR 光谱、质谱和 X 射线晶体学进行了表征。
AS2 被鉴定为贝壳杉-16-烯-19-酸（KA），一种二萜。AS2 的口服 LD₅₀为 3800mg/kg。结果表明，MME、EF 和 AS2 显著（P<0.05）且呈剂量依赖性地延迟了 PTZ 和最大电休克（MES）诱导的肌阵挛性痉挛和强直-阵挛相的发作开始。
在安诺那根皮提取物中鉴定出贝壳杉烯酸为抗惊厥成分。MME、EF 和 AS2 的抗惊厥作用可能是通过中枢抑制机制介导的。
