My 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. Current research focuses primarily on the biological activity of natural small molecule compounds (NSMC) as well as elucidation of the mechanisms underlying NSMC metabolism and the role that these compounds play in health and disease.
It is very intense and significative in the search for novel neuropharmacological 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 γ-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 α1β2γ2 and α5β2γ2 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 μM), suggesting the neuropharmacological 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 rotarod 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 myorelaxant side-effects typical of BZDs.
Heung-Bin Lim is a Professor at Chungbuk National University, Republic of Korea. He administers the Tobacco Smoke Analysis Center, an internationally recognized testing laboratory (KOLAS, KS Q ISQ / IEQ 17025), which analyzes the smoke components of all tobacco produced in Republic of Korea.
Pyrrolizidine alkaloids (PAs) are secondary metabolites biosynthesized in plants and are found in about 6,000 plants. Among these, the 1,2-unsaturated PAs, reported to be widely present in medicinal plants belonging to Asteraceae, Boraginaceae, and Fabaceae, cause hepatotoxicity and genotoxicity in humans and animals. Hence, there is a need for an analytical method that allows these dangerous plant toxins to be determined. In this study, we developed a method that can be used for the rapid and accurate determination of nine toxic PAs in medicinal plants using ultra-pressure liquid chromatography–electrospray ionization–quadrupole–time-of-flight mass spectrometry (UPLC-ESI-Q-TOF). The compounds were eluted onto a C18 column with 0.1% formic acid and acetonitrile, and separated with good resolution within 11 min. Each component was characterized by its precursor ions (generated by ESI-Q-TOF) and fragment ions (produced by collision-induced dissociation, CID), which were used as a reliable database. The proposed analytical method was verified with reference to the ICH guidelines. The results showed excellent linearity (R2 > 0.9951), limit of detection (2 to 12 ng/mL), limit of quantification (6 to 30 ng/mL), intra-day and inter-day precisions, and extraction recovery rates (76.9% to 103.3%) for all components. The validated UPLC-ESI-Q-TOF method was applied to medicinal plants belonging to the family Asteraceae, and senkirkine and senecionine were detected in Tussoilago farfara. In addition, with regard to the extraction efficiency of these two alkaloids, the QuEchERS method was the most efficient in comparison with methods like hot water and ethanol. The present results demonstrate that the proposed UPLC-ESI-Q-TOF method can be employed for the screening and quantification of toxic alkaloids in medicinal plants.