Objectives: Kadsura longipedunculata (KL) has been widely used for the treatment of insomnia in traditional Chinese medicine. The aim of this study was to explore the mechanism of the sedative and hypnotic effects of KL.
Materials And Methods: The content of KL was evaluated by HPLC-TOF-MS, and a potential target was found and used to construct its 3D structure to screen for potential ligands among the compounds in KL by using bioinformatics analysis, including similarity ensemble approach (SEA) docking, homology modeling, molecular docking and ligand-based pharmacophore. The PCPA-induced insomnia rat model was then applied to confirm the potential targets related to the sedative effects of KL by performing the forced swimming test (FST), the tail suspension test (TST) and the measurement of target-related proteins using western blotting and immunofluorescence.
Results: Bioinformatics analysis showed that most of lignan compounds in KL were optimal ligands for the 5-HT1A receptor (5-HT1AR), and they were found to be potential targets related to sedative effects; the main lignan content of KL extracts was characterized by HPLC-TOF-MS, with 7 proposed lignans detected. Administration of KL could significantly reduce FST and TST immobility time in the PCPA-induced 5HT-depleted insomnia rat model. The expressions of proteins related to the 5-HT1AR pathway were regulated by extracts of KL in a concentration-dependent manner, indicating that extracts of KL had 5-HT1AR agonist-like effects.
Conclusion: In silico analysis and experimental validation together demonstrated that lignan extracts from KL can target 5-HT1AR in insomniac rats, which could shed light on its use as a potential 5-HT1AR agonist drug.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468062 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130055 | PLOS |
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