NHBA isolated from Gastrodia elata exerts sedative and hypnotic effects in sodium pentobarbital-treated mice.
The rhizomes of Gastrodia elata have been used for the treatment of insomnia in oriental countries. N⁶-(4-hydroxybenzyl) adenine riboside (NHBA) was originally isolated from G. elata. For the first time we report a detailed study on the effects and mechanisms of NHBA on its sedative and hypnotic activity. Adenosine, an endogenous sleep factor, regulates sleep-wake cycle via interacting with adenosine A₁/A(2A) receptors. Using radioligand binding studies and cAMP accumulation assays, our results show that NHBA may be a functional ligand for the adenosine A₁ and A(2A) receptors. NHBA significantly decreases spontaneous locomotor activity and potentiates the hypnotic effect of sodium pentobarbital in mice. Sleep architecture analyses reveal that NHBA significantly decreases wakefulness time and increases NREM sleep times. However, NHBA does not affect the amount of REM sleep. Pretreatment with the adenosine A₁ receptor antagonist DPCPX or the A(2A) receptor antagonist SCH 58261 significantly reverses the increase in sleeping time induced by NHBA in sodium pentobarbital treated mice. Immunohistochemical studies show that NHBA increases c-Fos expression in GABAergic neurons of the ventrolateral preoptic area (VLPO), which suggests that NHBA activates the sleep center in the anterior hypothalamus. Altogether, these results indicate that NHBA produces significant sedative and hypnotic effects. Such effects might be mediated by the activation of adenosine A₁/A(2A) receptors and stimulation of the sleep center VLPO.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Ying
Y
Zhang
Min
M
Li
Rui-Xia
RX
Kang
Jian-Gong
JG
Shi
Geng-Tao
GT
Liu
Jian-Jun
JJ
Zhang
D000241:Adenosine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004569:Electroencephalography / Q000187:drug effects; D031668:Gastrodia / Q000737:chemistry*; D006993:Hypnotics and Sedatives; D007150:Immunohistochemistry; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D012018:Reflex / Q000187:drug effects
D006993:Hypnotics and Sedatives; C519742:N6-(4-hydroxybenzyl)adenine riboside; D016760:Proto-Oncogene Proteins c-fos; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D000242:Cyclic AMP; D010424:Pentobarbital; D000241:Adenosine