Sedative effects of peanut (Arachis hypogaea L.) leaf aqueous extracts on brain ATP, AMP, Adenosine and Glutamate/GABA of rats

Xiao-Yan Zu, Zhen-Ya Zhang, Ji-Qiang Liu, Hong-Hai Hu, Guo-Qing Xing, Ying Zhang, Di Guan
DOI: 10.4236/jbise.2010.33036                

Abstract

Peanut (Arachis hypogaea L.) leaf aqueous extracts (PLAE) has been reputed to be a type of sleep-aid in China. To investigate the sedative effects and effect pathways of PLAE, rats (n = 31) were employed in two experiments and intragastrically administrated of (1) distilled water, PLAE (500 mg/kg body weight (BW)) and peanut stem aqueous extracts (PSAE, 500 mg/kg BW); (2) 0, 100 or 500 mg/kg BW of PLAE, respectively for at least 14 days. Six relevant neurotransmitters were measured finally. Experiment-1 (n = 16) results showed that the brain Lactate were significantly elevated (p < 0.05) in rat cerebrums after PLAE administrations, compared with Control and PSAE groups. In respect of brain energy system, significant degradations of the brain adenosine triphos- phate (ATP) (p < 0.05) were observed in the brainstems and even the whole brains of rats though PLAE treatments. Moreover, we found that the brain Adenosine monophosphate (AMP) were clearly decreased (p < 0.05) in rat cerebrum and brainstem regions, while the brain Adenosine revealed an increasing propensity (p = 0.076) in the cerebrums of freely behaving rats. After experiment-2 (n = 15), the γ-aminobutyric acid (GABA) concentrations were statistically (p < 0.05) enhanced and the ratios of Glutamate/GABA were simultaneously reduced (p < 0.05) in rat brainstems, no matter which one dose (100 or 500 mg/kg BW) of PLAE were used. Results indicated that PLAE could influence the target neurotransmitters that related to rat circadian rhythms in the specific brain regions, possessing the potentialities as a sedative or sleep-aid for hypnic therapy purposes.

Keywords

Arachis Hypogaea L. Leaf Aqueous Extracts; Sedative Effects; Rats; Neurotransmitters

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Diana, M.T., Carol, A.L., Heidi, P. and Michael, V.V. (2007) A systematic review of valerian as a sleep aid: Safe but not effective. Sleep Medicine Reviews, 11, 209-230.
[2]	Wang, Q.C., Xu, J. and Shi, M. (2001) Clinical efficacy of Groundnut leaves on insomnia treatments. Shanghai Journal of Traditional Chinese Medicine, 5, 8-10.
[3]	Hu, P.F., Fan, R.P., Li, Y.P. and Pang, C.Y. (2001) Studies on pharmacological action of Luohuashengzhiye extracts. Chinese Traditional Patent Medicine, 23, 919- 920.
[4]	Wang, Y.F., Li, H.F., Xu, Y.F., Zhang, Y.L., Xu, D.S., Xiao, L.M. and Li, X.M. (2001). Clinical confirmation of preparation from the branch and leaf of peanut in treating insomnia. Shanghai Journal of Traditional Chinese Medicine, 35, 8-10.
[5]	Saper, C.B., Scammell, T.E. and Lu, J. (2005) Hypothalamic regulation of sleep and circadian rhythms. Nature, 437, 1257-1263.
[6]	Jones, B.E. (2005) From waking to sleeping: Neuronal and chemical substrates. Trends in Pharmacological Sciences, 26, 578-586.
[7]	Thakkar, M.M., Engemann, S.C., Walsh, K.M. and Sahota, P.K. (2008) Adenosine and the homeostatic control of sleep: Effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness. Neuroscience, 153, 875-880.
[8]	Schweinsberg, P.D. and Loo, T.L. (1980) Simultaneous analysis of ATP, ADP, AMP, and other purines in human erythrocytes by high-performance liquid chromatography. Journal of Chromatography, 181, 103-107.
[9]	Dworak, M., Diel, P., Voss, S., Hollmann, W.K. and Strüder, H. (2007) Intense exercise increases adenosine concentrations in rat brain: Implications for a homeostatic sleep drive. Neuroscience, 150, 789-795.
[10]	Huang, Z.L., Urade, Y. and Hayaishi, O. (2007) Prostaglandins and adenosine in the regulation of sleep and wakefulness. Current Opinion in Pharmacology, 7, 33-38.
[11]	Kalinchuk, A.V., Urrila, A.S., Alanko, L., Heiskanen, S., Wigren, H.K., Suomela, M., Stenberg, D. and Porkka- Heiskanen, T. (2003) Local energy depletion in the basal forebrain increases sleep. European Journal of Neuroscience, 17, 863-869.
[12]	Wigren, H.K., Schepens, M., Matto, V., Stenberg, D. and Porkka-Heiskanen, T. (2007) Glutamatergic stimulation of the basal forebrain elevates extracellular adenosine and increases the subsequent sleep. Neuroscience, 147, 811-823.
[13]	Maloney, K.J., Mainville, L. and Jones, B.E. (1999) Differential c-Fos expression in cholinergic, mono-aminergic and GABAergic cell groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation and recovery. Neuroscience, 19, 3057-3072.
[14]	Maloney, K.J., Mainville, L. and Jones, B.E. (2000) c-Fos expression in GABAergic, serotonergic and other neurons of the pontomedullary reticular formation and raphe after paradoxical sleep deprivation and recovery. Neuroscience, 20, 4669-4679.
[15]	Sherin, J.E., Shiromani, P.J., McCarley, R.W. and Saper, C. B. (1996) Activation of ventrolateral preoptic neurons during sleep. Science, 271, 216-219.
[16]	Martin, L.J., Blackstone, C.D., Levey, A.I., Huganir, R. L. and Price, D.L. (1993) Cellular localizations of AMPA glutamate receptors within the basal forebrain magnocellular complex of rat and monkey. Neuroscience, 13, 2249-2263.
[17]	Page, K.J. and Everitt, B.J. (1995) The distribution of neurons coexpressing immunoreactivity to AMPA- sensitive glutamate receptor subtypes (GluR1-4) and nerve growth factor receptor in the rat basal forebrain. European Journal of Neuroscience, 7, 1022-1033.
[18]	Cape, E.G. and Jones, B.E. (2000) Effects of glutamate agonist versus procaine microinjections into the basal forebrain cholinergic cell area upon gamma and theta EEG activity and sleep-wake state. European Journal of Neuroscience, 12, 2166-2184.
[19]	Fournier, G.N., Materi, L.M., Semba, K. and Rasmusson, D.D. (2004) Cortical acetylcholine release and electroencephalogram activation evoked by ionotropic glutamate receptor agonists in the rat basal forebrain. Neuroscience, 123, 785-792.
[20]	Bown, A.W. and Shelp, B.J. (1997) The metabolism and functions of γ-aminobutyric acid. Plant Physiology, 115, 1-5.
[21]	Schousboe, A., Westergaard, N., Sonnewald, U., Petersen, S.B., Yu, A.C. and Hertz, L. (1992) Regulatory role of astrocytes for neuronal biosynthesis and homeostasis of glutamate and GABA. Progress in Brain Research, 94, 199-211.
[22]	Alam, M.A. and Mallick, B.N. (2008) Glutamic acid stimulation of the perifornical-lateral hypothalamic area promotes arousal and inhibits non-REM/REM sleep. Neuroscience Letters, 439, 281-286.