Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice.
Chlorogenic acid is a major polyphenolic component of many plants and beverages, and is particularly abundant in coffee. We evaluated the neuroprotective effects of chlorogenic acid on learning and memory impairment induced by scopolamine (0.5 mg/kg, i.p.), a muscarinic antagonist, using the Y-maze, passive avoidance, and Morris water maze tests. The chlorogenic acid significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze test, and significantly reversed cognitive impairments in mice as measured by the passive avoidance test. In addition, chlorogenic acid decreased escape latencies in the Morris water maze test. In a probe trial session, chlorogenic acid increased the latency time in the target quadrant in a dose-dependent manner. Ex vivo, chlorogenic acid inhibited acetylcholinesterase activity in the hippocampus and frontal cortex. Chlorogenic acid also decreased malondialdehyde levels in the hippocampus and frontal cortex. In vitro, chlorogenic acid was found to inhibit acetylcholinesterase activity (IC₅₀=98.17 μg/ml) and free radical scavenging activity (IC₅₀=3.09 μg/ml) in a dose-dependent manner. These results indicate that chlorogenic acid may exert anti-amnesic activity via inhibition of acetylcholinesterase and malondialdehyde in the hippocampus and frontal cortex.
Kwon
Seung-Hwan
SH
Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Lee
Ha-Kyung
HK
Kim
Ji-Ah
JA
Hong
Sa-Ik
SI
Kim
Hyoung-Chun
HC
Jo
Tae-Hyung
TH
Park
Young-In
YI
Lee
Chong-Kil
CK
Kim
Yong-Bin
YB
Lee
Seok-Yong
SY
Jang
Choon-Gon
CG
D000110:Acetylcholinesterase; D000544:Alzheimer Disease / Q000188:drug therapy; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D058851:GPI-Linked Proteins; D018727:Muscarinic Antagonists; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D002726:Chlorogenic Acid; D008315:Malondialdehyde; D000110:Acetylcholinesterase; C548245:Ache protein, mouse