Neuropharmacological evaluation of diethylether extract and xanthones of Gentiana kochiana.
Diethylether extract of aerial parts of Gentiana kochiana mostly consists of two tetraoxygenated xanthones: gentiacaulein (1,7-dihidroxy-3,8-dimethoxyxanthone; 76.1%) and gentiakochianin (1,7,8-trihidroxy-3-methoxyxanthone; 14.2%). The extract and these xanthones were evaluated for the CNS pharmacological activity in rodents. In vitro assays on rat brain preparations revealed insignificant interaction of the compounds with the specific dopamine and serotonin receptors or synaptosomal uptake of serotonin. However, the extract and gentiacaulein strongly inhibited rat microsomal MAO A (IC50=0.22 microg/ml and 0.49 microM, respectively). Their effects on MAO B and a gentiakochianin blocking potential on both MAO enzymes were moderate. Behavioral examinations on mice showed that 10 day s.c. administration of the extract (20 mg/kg) significantly decreased immobility score in a forced swimming test and strongly inhibited ambulation and stereotypy in an open-field test. These effects resembled those induced by 10 mg/kg imipramine. The ex vivo MAO A activity in crude brain mitochondrial fraction of mice treated with 20 mg/kg of the extract was significantly elevated, whilst that outside brain nerve terminals was declined. This study suggests some antidepressant therapeutic potential of G. kochiana, particularly of gentiacaulein, with an ambiguity whether pharmacological mechanism could be related only to the central inhibition of MAO A.
Tomić
Mirko
M
Department of Biochemistry, Institute for Biological Research, 29 novembra 142, 11060 Belgrade, Serbia and Montenegro. mitomic@ibiss.bg.ac.yu
Tovilović
Gordana
G
Butorović
Biljana
B
Krstić
Dijana
D
Janković
Teodora
T
Aljancić
Ivana
I
Menković
Nebojsa
N
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D004986:Ether / Q000737:chemistry; D030012:Gentiana; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000493:pharmacokinetics; D013550:Swimming; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
D010936:Plant Extracts; D011985:Receptors, Serotonin; D044004:Xanthones; C479001:gentiacaulein; D004986:Ether; D012701:Serotonin; C479000:gentiakochianin; D008995:Monoamine Oxidase; D007099:Imipramine; D004298:Dopamine