Luteolin mediates the antidepressant-like effects of Cirsium japonicum in mice, possibly through modulation of the GABAA receptor.
Cirsium japonicum (CJ) has been shown to possess antidepressant-like properties. In the present study, we sought to identify which constituent of CJ might be responsible for its antidepressant effects and determine probable mechanism of action. The ethanol extract of CJ was administered to mice then behavioral changes were evaluated in the forced-swimming test (FST) and open-field test (OFT). In addition, its effects on norepinephrine (NE) reuptake and intracellular chloride (Cl(-)) flux were determined, in vitro. The effects of CJ's major constituents (linarin, pectolinarin, chlorogenic acid, luteolin) were also evaluated. CJ showed antidepressant-like effect by significantly reducing immobile behavior of mice in the FST, without increasing locomotor activity in the OFT. CJ had no effect on monoamine (NE) uptake, but it significantly promoted Cl(-) ion influx in human neuroblastoma cells. This CJ-induced Cl(-) influx was significantly blocked by co-administration of the competitive GABAA receptor antagonist, bicuculline. Among the major constituents of the CJ extract, only luteolin produced similar antidepressant-like effect, in vivo, and Cl(-) ion influx, in vitro. Altogether, the present results suggest that the antidepressant-like effect of CJ was most probably induced by its constituent luteolin, mediated through potentiation of the GABAA receptor-Cl(-) ion channel complex.
Department of Pharmacy, Uimyung Research Institute for Neuroscience, Sahmyook University, 26-21 Kongneung-2-dong, Nowon-gu, Seoul, 139-742, Republic of Korea.
June Bryan I
JB
de la Peña
Chong Ah
CA
Kim
Hye Lim
HL
Lee
Seo Young
SY
Yoon
Hee Jin
HJ
Kim
Eun Young
EY
Hong
Gun Hee
GH
Kim
Jong Hoon
JH
Ryu
Yong Soo
YS
Lee
Kyeong Man
KM
Kim
Jae Hoon
JH
Cheong
D000818:Animals; D000928:Antidepressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D018118:Chloride Channels / Q000378:metabolism; D031180:Cirsium / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D047311:Luteolin / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013550:Swimming; D014162:Transfection
D000928:Antidepressive Agents; D018118:Chloride Channels; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010936:Plant Extracts; D011963:Receptors, GABA-A; C493227:SLC6A2 protein, human; D047311:Luteolin