Hypnotic effects and binding studies for GABA(A) and 5-HT(2C) receptors of traditional medicinal plants used in Asia for insomnia.
OBJECTIVE
Many medicinal plants have been used for treatment of insomnia in Asia. However, scientific evidence and precise mechanism for their sedative-hypnotic activity have not been fully investigated. Thus, we investigated the binding activity of the oriental plant extracts (mainly from Korea and Japan) to the well-known molecular targets for sleep regulation, GABA(A) and 5-HT(2C) receptors. Following the binding assay, sedative-hypnotic effects of the extracts with high affinity were examined in an animal model of sleep.


METHODS
Aqueous and ethanol extracts of 15 medicinal plants were tested for binding at the benzodiazepine site of GABA(A) receptor and 5-HT site of 5-HT(2C) receptor. The sedative-hypnotic effects of selected extracts were evaluated by measuring the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of extracts.


RESULTS
In the GABA(A) assay, the ethanol extracts of licorice and danshen displayed concentration-dependent, high affinity binding, whereas in the 5-HT(2C) assay, the ethanol extracts of ginseng and silk tree showed high affinity. Among these extracts we tested previously uncharacterized licorice and silk tree for hypnotic effects. We found the ethanol extracts of licorice and silk tree significantly decreased sleep latency and increased sleep duration in pentobarbital-induced sleep.


CONCLUSIONS
We demonstrate for the first time that licorice and silk tree have the sedative-hypnotic activity possibly by modulating GABA(A) and 5-HT(2C) receptors. We propose that licorice and silk tree might be effective candidates for treatment of insomnia.
Cho
Sueng-Mock
SM
Research Division of Food Industry Promotion, Korea Food Research Institute, Seongnam 608-737, Republic of Korea.
Shimizu
Makoto
M
Lee
C Justin
CJ
Han
Dae-Seok
DS
Jung
Cheol-Kyun
CK
Jo
Jin-Ho
JH
Kim
Young-Myoung
YM
D000818:Animals; D001208:Asia; D006993:Hypnotics and Sedatives / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008518:Medicine, East Asian Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry* / Q000254:growth & development; D011485:Protein Binding; D011869:Radioligand Assay; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000378:metabolism
D006993:Hypnotics and Sedatives; D010936:Plant Extracts; D044405:Receptor, Serotonin, 5-HT2C; D011963:Receptors, GABA-A