Mechanisms Of Ginkgo Biloba Extract Components In The Treatment Of Epilepsy Based On Systematic Pharmacology

As a global neurological disease,epilepsy affects more than 50 million people,and the continuous brain damage still plagues patients.Despite a series of genes have been found,unravelling the underlying molecular mechanism of epilepsy is still a major challenge.And because of one-third of patients with epilepsy cannot respond to anti-epilepsy drugs,seeking for complementary and alternative therapies,especially the traditional herbal treatments used in traditional Chinese medicine(TCM),is also an effective way to cure epilepsy.The traditional herbs to treat epilepsy has long been recorded in "The Yellow Emperor's Canon of Medicine".Compared with western medicine with single ingredient,the chemical composition of traditional Chinese medicine is complicated,the complexity and empirical nature of TCM demonstration and its effectiveness in the treatment of epilepsy cannot be fully guaranteed.Therefore,there is an urgent need for systematic development,which is suitable for screening of natural compounds in herbal medicine and the mechanism research.In this study,combined with the network system pharmacology research developed by the laboratory and western blot experiments,we revealed the therapeutic effect of ginkgo bilobalide B,a small molecule in ginkgo biloba leaves,on epilepsy.Through network system pharmacological analysis and experimental verification,we found its possible new mechanism of action.The main research contents are as follows:?.Through ADME screening,26 compounds with active pharmacokinetic properties were obtained from Ginkgo biloba;compound-target network analysis showed that the candidate active molecules of Ginkgo biloba acted on 297 target proteins,and the compounds or targets in the network showed the multi-directional pharmacological properties,indicating synergistic effects of Ginkgo biloba for treating diseases.?.Disease association analysis confirmed that 144 targets of Ginkgo biloba have therapeutic activity for mental disorders,and these targets can be significantly enriched to 101 pathways,among which the pathways related to the nervous system are significantly enriched.Combining the mapping of targets on pathways,the result reveals that Ginkgo biloba exerts a therapeutic effect through three signaling pathways of neuroactive ligand-receptor interaction,serotoninergic synapses,and dopaminergic synapses.?.It was found that GDF10 turn into the two networks of serotoninergic synapses and dopaminergic synapses through the TGF-? signaling pathway to demonstrate itspsychotherapeutic mechanism.Therefore,further experimental verification was performed,and Ginkgolide B was administered to rat epilepsy model and SH-SY5 Y cells in vitro to evaluate the antiepileptic effect of Ginkgo biloba and Ginkgolide B.Overall,this study focused on a multifunctional system network of active small molecule compounds of Ginkgo biloba,and systematically elucidated Ginkgo biloba extract in the treatment of epilepsy from the perspective of TCM molecules,pharmacodynamic targets and disease signaling pathways.The multi-component synergistic mechanism provides a certain theoretical basis for epilepsy treatment and new drug development,and also provides a new direction for the modernization of TCM.