CNS active principles from selected Chinese medicinal plants

In order to identify potential central nervous system (CNS) active principles from plants, 10 Chinese herbs have been selected from literature reports, namely Schefflera bodinieri, Schefflera delavayi, Celastrus angulatus, Celastrus orbiculatus, Clerodendrum mandarinorum, Clerodendrum bungei, Periploca callophylla, Periploca forrestii, Alangium plantanifolium and Uncaria rhynchophylla. These plants were extracted by 70% ethanol and biologically screened by receptor ligand binding assays which included α1-adrenoceptor, α2-adrenoceptor, β-adrenoceptor, 5HT1, 5HT1A, 5HT1C, 5HT2, opiate, benzodiazepine, Ca++-ion channel(DHP), K+-ion channel, dopamine 1, dopamine 2, adenosine 1, muscarinic, histamine 1, Na+/K+ ATPase, GABAA and GABAB receptors. The results of extract screening showed that all these plants were able to inhibit the specific binding of radioligands to at least one receptor at concentrations of 1 mg/ml. Four of the species were then selected according to their distinct biological activities for further investigation in order to isolate their active principles , A total of forty-two compounds have been obtained by combination of various chromatographic techniques and their structures were determined by spectroscopic methods. The complete interpretation of all the spectra has been achieved and twelve compounds were found to be of novel structure. From Schefflera bodinieri leaves and roots, fourteen triterpenoids and oligosaccarides have been obtained and eleven of them are novel. The extract screening showed that the plant was able to bind to α1 and α2 adrenoceptors, 5HT1, 5HT2, opiate, adenosine 1, Ca++-ion channel (DHP), K+-ion channel, dopamine 1, dopamine 2, GABAA and GABAB receptors. In further screening, two compounds isolated from the plant bound to the 5HT2 receptor, one compound bound to the Ca++-ion channel receptor, one compound bound to the dopamine 2 receptor and three compounds bound to the muscarinic receptor (IC50 0.9-8.0 μM). Five of the compounds had interactions with agonists or antagonists of α-adrenoceptor, Ca++-ion channel, 5HT1C, 5HT1A, 5HT2, histamine 1, K+-ion channel or adenosine 1 receptors decreasing their IC50 values and some of these compounds were able to influence the binding sites of the receptors. The present investigation has resulted in the isolation of different chemical types of CNS active principles including triterpenoids and their glucosides, oligosaccarides, flavonoids, phenols and alkaloids. The majority of clinical medicines in use are nitrogen-containing compounds, therefore it is possible that new non-nitrogen containing drugs may be developed from a knowledge of the structures identified in the present investigation. Plant medicines contain a mixture of chemical substances and their clinical efficacy cannot always be correlated with a single chemical component. The present results show that individual compounds may react with a single receptor or with a number of different receptors or affect other compound binding to receptors. The application of receptor ligand binding assays to plant extracts and their individual principles will further our understanding of the action of plant medicines