Medicinal & Aromatic Plants
Open Access
ISSN: 2167-0412
ISSN: 2167-0412
Zenggen Liu, Yun Shao, Martin Wallner, Yanduo Tao and Richard Olsen
Chinese Academy of Sciences, China
Tibetan Medicine Research, China
University of California, USA
Scientific Tracks Abstracts: Medicinal & Aromatic Plants
It is very intense and significative in the search for novel neuro pharmacological activities devoid of undesirable side-effects typical of classical Benzodiazepines (BZDs) in recent years and flavonoids, as a relative new class of ligands, have been shown to possess some anxiolytic and anticonvulsant effects in vivo/vitro. The objective of the present work was to evaluated the pharmacological properties of a naturally occurring flavonoid (2�??, 4�??, 5, 7-tetrahydroxy-5�?? 6-dimethoxyflavone or DMB) at recombinant ã-aminobutyric acid-A (GABA-A) receptors and its anti-alcohol, anxiolytic and anticonvulsant activities were tested by the models of animal behavior. DMB isolated from traditional Tibetan herb (Arenaria kansuensis), positively modulated GABA-activated current at á1â2ã2 and á5â2ã2 GABA-A receptors expressed in HEK 293T cells. The behavioral studies showed that DMB at doses of 0.5-8.0 mg/kg (I.P.) exerted significant anti-alcohol effects in the loss of righting reflex assay (P<0.01). The anxiolytic activity was measured on an elevated plus maze and the results indicated that DMB can alleviated significantly anxiety at the doses of 2-8 mg/kg (P.O.). Both DMB anti-alcohol and anxiolytic effects on animal behavior were antagonized by flumazenil (5 mg/kg in vivo), the BZD antagonist. DMB competitively inhibited BZD-site [3H] flunitrazepam binding (IC50, 0.10 ìM), suggesting the neuro pharmacological activities of DMB were mediated via the BZD-sites on GABA-A receptors. In addition, DMB (0.5-8.0 mg/kg, I.P.) exerted dose-dependently anticonvulsant activity in pentylenetetrazole induced seizure paradigms (P<0.01). Furthermore, DMB did not cause myorelaxant effects in the rota rod test and horizontal wire test. Therefore, the results of the present study suggest that the pharmacological activities (anti-alcohol, anxiolytic and anticonvulsant) of DMB are probably mediated through positive allosteric modulation of the different GABA-A receptor subtypes via interaction at the BZD-site and these effects were not accompanied by myo-relaxant side-effects typical of BZDs.
Zenggen Liu has his research interest is extraction, separation and identification of chemical composition from Traditional Tibetan Medicine, as well as activity screening of natural products and its derivatives.
E-mail: lzg@nwipb.cas.cn