Interactions of Magnolia and Ziziphus extracts with selected central nervous system receptors.
BACKGROUND
Magnolia officinalis Rehder and Wilson [Magnoliaceae] bark and Ziziphus spinosa (Buhge) Hu ex. Chen. [Fam. Rhamnaceae] seed have a history of use in traditional Asian medicine for mild anxiety, nervousness and sleep-related problems.


OBJECTIVE
To identify pharmacological targets, extracts of Magnolia officinalis (ME), Ziziphus spinosa (ZE), and a proprietary fixed combination (MZE) were tested for affinity with central nervous system receptors associated with relaxation and sleep.


METHODS
In vitro radioligand binding and cellular functional assays were conducted on: adenosine A(1), dopamine (transporter, D(1), D(2S), D(3), D(4.4) and D(5)), serotonin (transporter, 5-HT(1A), 5-HT(1B), 5-HT(4e), 5-HT(6) and 5-HT(7)) and the GABA benzodiazepine receptor.


RESULTS
Interactions were demonstrated with the adenosine A(1) receptor, dopamine transporter and dopamine D(5) receptor (antagonist activity), serotonin receptors (5-HT(1B) and 5-HT(6) antagonist activity) and the GABA benzodiazepine receptor at a concentration of 100 microg/ml or lower. ME had an affinity with adenosine A(1) (K(i) of 9.2+/-1.1 microg/ml) and potentiated the GABA activated chloride current at the benzodiazepine subunits of the GABA receptor (maximum effect at 50 microg/ml). ME had a modest antagonist action with 5-HT(6) and ZE with the 5-HT(1B) receptor.


CONCLUSIONS
The interactions in the receptor binding models are consistent with the traditional anxiolytic and sleep-inducing activities of Magnolia officinalis bark and Ziziphus spinosa seed.
Koetter
Uwe
U
Dr. Koetter Consulting, Kirchhalde 19, Uttwil 8592, Switzerland.
Barrett
Marilyn
M
Lacher
Svenja
S
Abdelrahman
Aliaa
A
Dolnick
Deanne
D
D000241:Adenosine / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D004338:Drug Combinations; D006801:Humans; D006993:Hypnotics and Sedatives / Q000737:chemistry* / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry*; D008518:Medicine, East Asian Traditional; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D043682:Receptor, Adenosine A1 / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D031957:Ziziphus / Q000737:chemistry*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D004338:Drug Combinations; D006993:Hypnotics and Sedatives; D009125:Muscle Relaxants, Central; D010936:Plant Extracts; D043682:Receptor, Adenosine A1; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D004298:Dopamine