Animal experiment: Zebrafish model successfully screened anti-epileptic active substances

  Epilepsy is a common brain dysfunction disease, which is specifically manifested as persistent epilepsy convulsions accompanied by nerve damage, employment disorders, mental illnesses and social disorders. The World Health Organization (WHO) estimates that there are approximately 500,000 people suffering from epilepsy worldwide. The incidence and causes of epilepsy vary according to age, gender, race, and socioeconomic status. Many kinds of epilepsy syndromes affect the nervous system in different forms. However, the final form of epilepsy is very similar. Whether it is triggered or spontaneous, it is caused by excessive discharge of brain cells. Although some people think that epilepsy is caused by brain damage, stroke, brain tumor or some genetic diseases, in most cases there are no factors that can be used to identify, and the formation mechanism of epilepsy is too complicated, and it is still unclear. Therefore, the action of suppressing epilepsy is an effective method to control epilepsy.

  After about 100 years of clinical experience, antiepileptic drugs (AEDs) are still the most important treatment, but these drugs often cause inevitable adverse effects on people's emotions and actions. In addition to synthetic epilepsy drugs, traditional Chinese medicines and natural extracts also account for a lot of market share in China. But due to the origin and collection time. Differences in treatment methods will affect the amount of active ingredients in the drug. Therefore, it is very important to establish a complete quality control system for the production of Chinese herbal medicines, which has attracted the attention of many companies.

  Zebrafish (Danio rerio), a small tropical freshwater fish with more than 71% homology to human protein coding genes, has been suggested as an alternative animal model to study the mechanism of epilepsy and screen anti-epileptic drugs. After induction of zebrafish with pentylenetetrazol, the central nervous system was affected. Zebrafish juveniles showed small spots and up-regulation of c-fos gene expression, consistent with epilepsy in humans and rodents. In addition, biochemical studies have shown that hormones, cytokines, and peripheral cell transcription all show consistency. Using 10 FDA approved epilepsy drugs, such as carbamazepine, phenytoin, sodium valproate, diazepam, gabapentin, levetiracetam, etc., experiments on zebrafish have also proved the stability and reliability.

  Researchers from the Shanghai Chinese Academy of Sciences and Huante Biology selected six new C21 steroid glycoside compounds, named cynotophyllosides AF (1-6) combined with 16 known compounds isolated from the roots of Qingyang ginseng (7 -22) The experiment was carried out and the results were published in the journal Natural products. Spectral and chemical analysis determined the main components of the new compound, including three compounds otophylloside F (15), otophylloside B (17) and rostratamine 3-O-β- D -oleandropyranosyl-(1→4)-β- D -cymaropyranosyl-(1→4)-β-D -cymaropyranoside (18) has a significant printing effect on the movement of epileptic zebrafish. Preliminary structure-activity analysis showed that the pregnane skeleton structure with C-12 ester group (ikemaoyl> cinnamoyl> hydroxy> p-hydroxybenzoyl) and a sugar chain structure consisting of three 2,6-dideoxysaccharides are the active sites.