Pharmacological characterization of orally active cholinesterase inhibitory activity of Prunus persica L. Batsch in rats.
Prunus persica L. Batsch water extract (PPE) is a potent acetylcholinesterase (AChE) inhibitor screened for the treatment of Alzheimer's disease. The effects of oral administration of the PPE were examined with comparison of those of selective butyrylcholinesterase inhibitors of 9-amino-1,2,3,4-tetrahydroacridine hydrochloride (tacrine) and tetraidopropylpyrophosphoramide (iso-OMPA) and a selective AChE inhibitor, donepezil, on the cholinesterase activity in the brain and plasma of rats. After the sequential solvent fractionation of the methanol extract of P. persica L. Batsch, the highest inhibitory fraction was that of chloroform (75%). The concentration that was required for 50% enzyme inhibition (IC(50) value) was 5.6 microg/mL for the chloroform fraction. Oral administration of PPE or tacrine caused a dose-dependent inhibition of brain and plasma cholinesterase activities. The ID(50) values of these compounds for brain cholinesterase activity were 2.7 g/kg and 8.9 mg/kg, respectively. On the other hand, the ID(50) values for plasma cholinesterase activity were 18.6 g/kg and 27.5 mg/kg, respectively. Thus, the ratios of the ID(50) (plasma < brain) were 6.0 and 3.1, respectively. These results suggest that orally administered PPE satisfactorily penetrates into the brain and inhibits cholinesterase there and that PPE is a potent inhibitor of brain cholinesterase in comparison with plasma cholinesterase in vivo.
Suh
Seok-Jong
SJ
Department of Biological Sciences, Sungkyunkwan University, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea.
Koo
Byung-Soo
BS
Jin
Un-Ho
UH
Hwang
Moon-Je
MJ
Lee
In-Seon
IS
Kim
Cheorl-Ho
CH
D000110:Acetylcholinesterase / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000378:metabolism*; D000077265:Donepezil; D007189:Indans / Q000378:metabolism; D008297:Male; D010880:Piperidines / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000378:metabolism*; D027861:Prunus / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013619:Tacrine / Q000008:administration & dosage / Q000378:metabolism; D014020:Tissue Extracts / Q000737:chemistry / Q000378:metabolism
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D010936:Plant Extracts; D014020:Tissue Extracts; D013619:Tacrine; D000077265:Donepezil; D000110:Acetylcholinesterase