Lancemaside A isolated from Codonopsis lanceolata and its metabolite echinocystic acid ameliorate scopolamine-induced memory and learning deficits in mice.
The rhizome of Codonopsis lanceolata (family Campanulaceae), which contains lancemaside A as a main constituent, has been used as herbal medicine to treat inflammation, insomnia, and hypomnesia. Lancemaside A and echinocystic acid, which is its metabolite by intestinal microflora, potently inhibited acetylcholinesterase activity in a dose-dependent manner, with IC₅₀ value 13.6 μM and 12.2 μM, respectively. Its inhibitory potency is comparable with that of donepezil (IC₅₀=10.9 μM). Lancemaside A and echinocystic acid significantly reversed scopolamine-induced memory and learning deficits on passive avoidance task. Lancemaside A orally administered 5h before treatment with scopolamine reversed scopolamine-induced memory and learning deficits more potently than one orally administered 1h before. Echinocystic acid more potently reversed it than lancemaside A. Lancemaside A and echinocystic acid significantly reversed scopolamine-induced memory and learning deficits on the Y-maze and Morris water maze tasks. Lancemaside A and echinocystic acid also increased the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (p-CREB). Based on these findings, orally administered lancemaside A may be metabolized to echinocystic acid, which may be absorbed into the blood and ameliorate memory and learning deficits by inhibiting AChE activity and inducing BDNF and p-CREB expressions.
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, 1 Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Il-Hoon
IH
Jung
Se-Eun
SE
Jang
Eun-Ha
EH
Joh
Jayong
J
Chung
Myung Joo
MJ
Han
Dong-Hyun
DH
Kim
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D029745:Codonopsis / Q000737:chemistry*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D007189:Indans / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010880:Piperidines / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D027343:Rhizome; D012601:Scopolamine
D019208:Brain-Derived Neurotrophic Factor; D002800:Cholinesterase Inhibitors; D017362:Cyclic AMP Response Element-Binding Protein; D007189:Indans; D010880:Piperidines; D010936:Plant Extracts; C580835:landemaside A; D009828:Oleanolic Acid; D000077265:Donepezil; D012601:Scopolamine; D000110:Acetylcholinesterase; C022999:echinocystic acid