TY - JOUR
T1 - Rhus parviflora and its biflavonoid constituent, rhusflavone, induce sleep through the positive allosteric modulation of GABA A-benzodiazepine receptors
AU - Shrestha, Sabina
AU - Park, Ji Hae
AU - Lee, Dae Young
AU - Cho, Jin Gyeong
AU - Cho, Suengmok
AU - Yang, Hye Jin
AU - Yong, Hye Im
AU - Yoon, Min Seok
AU - Han, Dae Seok
AU - Baek, Nam In
PY - 2012/6/26
Y1 - 2012/6/26
N2 - Ethnopharmacological relevance: Rhus parviflora is referred as 'Tintidikah' in traditional medicinal system of south Asia (Ayurveda). It is used in treatment of Vāta vikāra, a condition related to neurological complications as well as cure for stomach disorders. Materials and methods: Dried and powdered fruits of R. parviflora were extracted with 80% aqueous methanol (RPME). The concentrated extract was successively partitioned with distilled water (DW), ethyl acetate (EtOAc), and n-butanol (n-BuOH). All extracts, as well as isolated biflavonoids from R. parviflora, were evaluated for their affinity to the benzodiazepine binding site of GABA A receptor. The sedative-hypnotic effects of the fractions were evaluated by measuring sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of the extract fractions. Results: Oral administration of RPME (125 mg/kg, 250 mg/kg, 500 mg/kg, and 1000 mg/kg) produced a dose-dependent decrease in sleep latency and an increase in sleep duration in mice treated with pentobarbital. The methanol extract produced a hypnotic effect that was fully blocked by 3H-Ro 15-1788 flumazenil (FLU). Further, among the solvent fractions, the ethyl acetate fraction exhibited significant activity. Among the isolated compounds, biflavonoids mesuaferrone B (1), rhusflavone (3), and agathisflavone (4) competitively inhibited FLU binding with a K i of 0.280 μM, 0.045 μM, and 0.091 μM, respectively. In addition, analysis of the sedative-hypnotic effects of rhusflavone, as well as those of the ethyl acetate, n-butanol, and distilled water fractions revealed that the modulation of both the ethyl acetate fraction and biflavonoid rhusflavone (3) are the most potent in inducing sleep. Conclusion: The presence of conjugated ketone and C6-C8″ biflavonoid linkage in rhusflavone may be responsible for BZD-site of the GABA A leading to decrease in sleep latency and increase sleep duration.
AB - Ethnopharmacological relevance: Rhus parviflora is referred as 'Tintidikah' in traditional medicinal system of south Asia (Ayurveda). It is used in treatment of Vāta vikāra, a condition related to neurological complications as well as cure for stomach disorders. Materials and methods: Dried and powdered fruits of R. parviflora were extracted with 80% aqueous methanol (RPME). The concentrated extract was successively partitioned with distilled water (DW), ethyl acetate (EtOAc), and n-butanol (n-BuOH). All extracts, as well as isolated biflavonoids from R. parviflora, were evaluated for their affinity to the benzodiazepine binding site of GABA A receptor. The sedative-hypnotic effects of the fractions were evaluated by measuring sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of the extract fractions. Results: Oral administration of RPME (125 mg/kg, 250 mg/kg, 500 mg/kg, and 1000 mg/kg) produced a dose-dependent decrease in sleep latency and an increase in sleep duration in mice treated with pentobarbital. The methanol extract produced a hypnotic effect that was fully blocked by 3H-Ro 15-1788 flumazenil (FLU). Further, among the solvent fractions, the ethyl acetate fraction exhibited significant activity. Among the isolated compounds, biflavonoids mesuaferrone B (1), rhusflavone (3), and agathisflavone (4) competitively inhibited FLU binding with a K i of 0.280 μM, 0.045 μM, and 0.091 μM, respectively. In addition, analysis of the sedative-hypnotic effects of rhusflavone, as well as those of the ethyl acetate, n-butanol, and distilled water fractions revealed that the modulation of both the ethyl acetate fraction and biflavonoid rhusflavone (3) are the most potent in inducing sleep. Conclusion: The presence of conjugated ketone and C6-C8″ biflavonoid linkage in rhusflavone may be responsible for BZD-site of the GABA A leading to decrease in sleep latency and increase sleep duration.
KW - Ayurveda
KW - Biflavonoid
KW - GABA type A-benzodiazeine receptor
KW - Hypnotic effects
KW - Rhusflavone Rhus parviflora
UR - http://www.scopus.com/inward/record.url?scp=84861983177&partnerID=8YFLogxK
U2 - 10.1016/j.jep.2012.04.047
DO - 10.1016/j.jep.2012.04.047
M3 - Article
C2 - 22579675
AN - SCOPUS:84861983177
SN - 0378-8741
VL - 142
SP - 213
EP - 220
JO - Journal of Ethnopharmacology
JF - Journal of Ethnopharmacology
IS - 1
ER -