Abstract
Insomnia is an important public health problem. The currently available treatments for insomnia can cause some adverse effects. Orexin receptors 1 (OX1R) and 2 (OX2R) are burgeoning targets for insomnia treatment. It is an effective approach to screening OX1R and OX2R antagonists from traditional Chinese medicine, which contains abundant and diverse chemical components. This study established an in-home ligand library of small-molecule compounds from medicinal plants with a definite hypnotic effect, as described in the Chinese Pharmacopoeia. Molecular docking was applied to virtually screen potential orexin receptor antagonists using molecular operating environment software, and surface plasmon resonance (SPR) technology was used to detect the binding affinity between potential active compounds and orexin receptors. Finally, the results of virtual screening and SPR analysis were verified through in vitro assays. We successfully screened one potential lead compound (neferine) as an orexin receptor antagonist from the in-home ligand library, which contained more than 1000 compounds. The screened compound was validated as a potential agent for insomnia treatment through comprehensive biological assays. This research enabled the discovery of a potential small-molecule antagonist of orexin receptors for the treatment of insomnia, providing a novel screening approach for the detection of potential candidate compounds for corresponding targets.