Tanshinone congeners improve memory impairments induced by scopolamine on passive avoidance tasks in mice.
Tanshinones are a group of diterpenoids found in the roots of Salvia miltiorrhiza Bunge which has been used to treat cardiac disease. In the present study, we investigated the effect of the tanshinone congeners, tanshinone I, tanshinone IIA, cryptotanshinone, and 15, 16-dihydrotanshinone I, on learning and memory impairments induced by scopolamine (1 mg/kg, i.p.), a muscarinic antagonist, using passive avoidance tasks in mice. Tacrine was used as a positive control. Tanshinone I (2 or 4 mg/kg, p.o.), tanshinone IIA (10 or 20 mg/kg, p.o.), cryptotanshinone (10 mg/kg, p.o.), and 15, 16-dihydrotanshinone I (2 or 4 mg/kg, p.o.) significantly reversed scopolamine-induced cognitive impairments (P<0.05). Tanshinone I (2 mg/kg, p.o.) and tanshinone IIA (10 or 20 mg/kg, p.o.) were also reversed diazepam-induced cognitive dysfunctions (P<0.05). In addition, cryptotanshinone and 15, 16-dihydrotanshinone I were found to have an inhibitory effect on acetylcholinesterase in vitro with IC(50) values 82 and 25 microM, respectively. Furthermore, cryptotanshinone inhibited acetylcholinesterase activity for 3 h and 15, 16-dihydrotanshinone I for 6 h in an ex-vivo study. These results suggest that tanshinone congeners may be useful for the treatment of cognitive impairment and that their beneficial effects are mediated, in part, by cholinergic signaling enhancement.
Kim
Dong Hyun
DH
Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, South Korea.
Jeon
Su Jin
SJ
Jung
Ji Wook
JW
Lee
Seungjoo
S
Yoon
Byung Hoon
BH
Shin
Bum Young
BY
Son
Kun Ho
KH
Cheong
Jae Hoon
JH
Kim
Yeong Shik
YS
Kang
Sam Sik
SS
Ko
Kwang Ho
KH
Ryu
Jong Hoon
JH
D045784:Abietanes; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005663:Furans; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D010616:Phenanthrenes / Q000494:pharmacology*; D011809:Quinones; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology*
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D005663:Furans; D010616:Phenanthrenes; D011809:Quinones; D011963:Receptors, GABA-A; C021751:tanshinone; C000713095:dihydrotanshinone I; C037886:cryptotanshinone; D012601:Scopolamine