Inhibitory effects of Glycyrrhizae radix and its active component, isoliquiritigenin, on Aβ(25-35)-induced neurotoxicity in cultured rat cortical neurons.
This study investigated an ethanol extract from Glycyrrhizae radix (GR), the root of Glycyrrhiza uralensis (Leguminosae), for possible neuroprotective effects on neurotoxicity induced by amyloid β protein (Aβ) (25-35) in cultured rat cortical neurons. Exposure of cultured cortical neurons to 10 μM Aβ (25-35) for 36 h induced neuronal apoptotic death. GR (10-50 μg/mL) prevented the Aβ (25-35)-induced neuronal apoptotic death, as assessed by a MTT assay and Hoechst 33342 staining. Furthermore, GR decreased the expression of Bax and active caspase-3, proapoptotic proteins, and increased Bcl-2, an antiapoptotic protein. GR also significantly inhibited Aβ (25-35)-induced elevation of the intracellular Ca(2+) concentration ([Ca(2+)](i)) and generation of reactive oxygen species (ROS) measured by fluorescent dyes. Isoliquiritigenin (1-20 μM), isolated from GR as an active component, inhibited Aβ (25-35)-induced neuronal apoptotic death, elevation of [Ca(2+)](i), ROS generation, and the change of apoptosis-associated proteins in cultured cortical neurons, suggesting that the neuroprotective effect of GR may be, at least partly, attributable to this compound. These results suggest that GR and isoliquiritigenin prevent Aβ (25-35)-induced neuronal apoptotic death by interfering with the increases of [Ca(2+)](i) and ROS, and GR may have a possible therapeutic role for preventing the progression of neurodegenerative disease such as Alzheimer's disease.
College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.
Hong Kyu
HK
Lee
Eun-Ju
EJ
Yang
Joo Youn
JY
Kim
Kyung-sik
KS
Song
Yeon Hee
YH
Seong
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047188:Chalcones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D006035:Glycyrrhiza / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D016229:Amyloid beta-Peptides; D047188:Chalcones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C040920:isoliquiritigenin