Periostracum Cicadae Extract and N-Acetyldopamine Regulate the Sleep-Related Neurotransmitters in PCPA‑Induced Insomnia Rats

Insomnia is the second most prevalent mental illness worldwide. Periostracum cicadae (PC), as an animal traditional Chinese medicine with rich pharmacological effects, has been documented as a treatment for children’s night cries, and later extended to treat insomnia. This study aimed to investigate the effects of PC extract and N-acetyldopamine compounds in ameliorating insomnia. The UPLC-ESI-QTOF-MS analysis determined that PC extract mainly contained N-acetyldopamine components. Previously, we also isolated some acetyldopamine polymers from PC extract, among which acetyldopamine dimer A (NADA) was present in high content. Molecular docking and molecular dynamic simulations demonstrated that NADA could form stable complexes with 5-HT1A, BDNF, and D2R proteins, respectively. The effects of PC extract and NADA on insomnia were evaluated in the PCPA-induced insomnia model. The results indicated that PC extract and NADA could effectively ameliorate hypothalamic pathology of insomnia rats, increase the levels of 5-HT, GABA, and BDNF, and decrease the levels of DA, DOPAC, and HVA. Meanwhile, the PC extract and NADA also could significantly affect the expression of 5-HT1A, BDNF, and DARPP-32 proteins. This study proved that PC extract and acetyldopamine dimer A could effectively improve PCPA‑induced insomnia in rats. It is speculated that the main pharmacological substances of PC were acetyldopamine components.