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Updated: Oct 13, 2025

Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella
Published on: November 30, 2018
Identification of Potential Human Ryanodine Receptor 1 Agonists and Molecular Mechanisms of Natural Small-Molecule
Yahong Chen1, Xiaohong Wang1, Haifeng Zhai2
1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Yangguang South Road, Fangshan District, Beijing 102488, China.
Abstract:
Natural small-molecule phenols (NSMPs) possess certain ubiquitous bioactivities including the anxiolytic effect. Ryanodine receptor 1 (RyR1) may be one of the potentially critical pharmacological targets for studying the anxiolytic activity of NSMPs. However, detailed molecular mechanisms of NSMPs have not been fully clarified. This research was intended to identify potent hRyR1 agonists from NSMPs and investigate whether RyR1 plays a role in their anxiolytic effect. Homology modeling and molecular docking analysis were performed using Accelrys Discovery Studio 2.5. The most appropriate concentrations of NSMPs to activate RyR1 were measured using the MTT assay. Fluorescence analyses of the intracellular calcium levels and western blotting analysis were carried out to validate whether NSMPs could regulate the calcium flux to some extent by activating RyR1. The results demonstrated that xanthotoxol and 5-hydroxy-1,4-naphthalenedione can be screened as hit compounds for potential agonists of hRyR1 to exert the anxiolytic effect. In conclusion, NSMPs might be a kind of pharmacological signal carrier, acting on RyR1 as an agonist and resulting in calcium ion mobilization from intracellular calcium ion store.
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