Natural neuroactive compounds isolated from medicinal plants

MARIEL MARDER

Facultad de Farmacia y Bioquímica, UBA, Argentina

Workshop; International Workshop Strategies for the development of new drugs; 2008

Herbs have been highly valued and used regularly for thousands of years by people all over the world as the medicine of the masses. Medicinal plants have been used to treat such psychotropic and behavioral conditions as anxiety, depression, seizures, poor memory, dementia, insomnia, and drug intoxication. Plants contain many complex substances that may account for the variety of the claimed medical uses. There is limited information regarding herb-drug and herb-herb interactions and their mechanisms, metabolism and excretion are largely unstudied. Also, herbal products are generally unregulated and often health claims are unsubstantiated or sometimes exaggerated. It must not be assumed that since an herb has been used for thousands of years the herb is necessarily safe and truly effective for its claimed indication. Studies from our laboratory have shown that flavonoids present in tranquillizing plants are responsible for most of their pharmacological properties, anxiolytic and sedative effects, which are probably exerted by a similar mechanism to that of benzodiazepines, since the active flavones are good ligands for the benzodiazepine binding site (BDZ-bs) of the GABAA receptor in the brain (Marder and Paladini, 2002; Medina et al., 1997). However, it was subsequently found that flavonoid glycosides, also present in tranquillizing plants, e.g. valeriana (Marder et al., 2003; Fernández et al., 2004 and 2006), although exerting central nervous system depressant effects, do not involve the GABAA receptor and the participation of the opioid receptors in their depressant activities was recently demonstrated for the most active derivative, hesperidin (Loscalzo et al., 2007). Relevant synergistic effects were found when a variety of mixtures of these glycosides with simple flavonoids, or even with benzodiazepines, were tested in vivo (Fernández et al., 2005 and 2006; Loscalzo et al, 2008).   Fernández SP, Wasowski C, Paladini AC, Marder M. Central nervous system depressant action of flavonoid glycosides. Eur J Pharmacol 2006; 539:168-76. Fernández SP, Wasowski C, Paladini AC, Marder M. Sedative and sleep enhancing properties of linarin, a flavonoid isolated from Valeriana officinalis. Pharmacol Biochem Behav 2004; 77:399-404. Fernández SP, Wasowski C, Paladini AC, Marder M. Synergistic interaction between hesperidin, a natural flavonoid, and diazepam. Eur J Pharmacol 2005; 512:189-98. Loscalzo LM, Wasowski C, Paladini AC, Marder M. Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Europ J Pharmacol 2008; 580: 306-313. Marder M, Paladini AC. GABAA-receptor ligands of flavonoid structure. Curr Top Med Chem 2002; 2:853-67. Marder M, Viola H, Wasowski C, Fernández S, Medina JH, Paladini AC. 6-Methylapigenin and hesperidin: new valeriana flavonoids with activity on the CNS. Pharmacol Biochem Behav 2003; 75:737-45. Medina JH, Viola H, Wolfman C, Marder M, Wasowski C, Calvo D, Paladini AC. Overview. Flavonoids: A new family of benzodiazepine receptor ligands. Neurochem Res 1997; 22:419-25.