1. Tandem mass tag-based proteomics reveals the antiepileptic mechanism of steroidal saponins from Anemarrhena asphodeloides in Kainic acid induced epileptic rat model.
- Author
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Zhang JJ, Guan W, Wang Y, Wang YX, An DQ, Hao ZC, Li MM, Kuang HX, Chen QS, Zhang LL, Liu Y, and Yang BY
- Subjects
- Animals, Rats, Male, Disease Models, Animal, Plant Extracts pharmacology, Plant Extracts chemistry, Proteome analysis, Proteome drug effects, Chromatography, High Pressure Liquid methods, Saponins pharmacology, Saponins chemistry, Epilepsy chemically induced, Epilepsy drug therapy, Epilepsy metabolism, Proteomics methods, Kainic Acid toxicity, Anemarrhena chemistry, Rats, Sprague-Dawley, Tandem Mass Spectrometry methods, Anticonvulsants pharmacology, Anticonvulsants chemistry
- Abstract
Epilepsy (EP) is one of the most common neurological diseases in the world. Anemarrhena asphodeloides Bunge. (AA), as a typical heat-cleaning medicine, has been proven to possess the antiepileptic effect in clinical and experimental studies. Anemarrhena asphodeloides steroidal saponins (AAS) are main components. However, the therapeutic effects and underlying mechanisms of AAS against EP are not been fully elucidated. In this study, 63 steroidal saponins were discovered in AAS by UPLC-Q-TOF/MS analysis. Pharmacological and behavioral analysis demonstrated that AAS could significantly lower the Racine classification and reduce the frequency of generalized spike rhythm the rate of tetanic seizures in kainic acid-induced epileptic rats. Hematoxylin and eosin and Nissl staining-indicated AAS could significantly improve hippocampal injury and neuron loss in epileptic rats. TMT proteomic analysis discovered 26 different expressed proteins (DEPs), which were identified as the rescue proteins. After bioinformatic analysis, Heat Shock Protein 90 Alpha Family Class B Member 1 (Hsp90ab1) and Tyrosine 3-Monooxygenase (Ywhab) were screened as key DEPs and verified by western blotting. AAS could significantly inhibited the up-regulation of Hsp90ab1 and Ywhab in EP rats; these two proteins might be the key targets of AAS in treating EP., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
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