期刊
BIOMOLECULES & THERAPEUTICS
卷 27, 期 6, 页码 584-590出版社
KOREAN SOC APPLIED PHARMACOLOGY
DOI: 10.4062/biomolther.2019.149
关键词
Luteolin; Sleep; Electroencephalogram; Adenosine A1 receptor; Adenosine A2A receptor; Insomnia
资金
- Commercialization Promotion Agency for R&D Outcomes (COMPA) - Ministry of Science and ICT (MSIT) [2018K000277]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI18C0920]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Republic of Korea [2018R1D1A1B07048729]
- National Research Foundation of Korea [2018R1D1A1B07048729] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer's disease. However, little information is available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptor-benzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine Al and A2A receptor (Al R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an Al R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with IC50 of 1.19, 0.84 mu g/kg, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through Al R and A2AR binding.
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