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Epilepsy is the most common chronic neurological disease, affecting about 1% of the world's population during their lifetime. Most people with epilepsy can attain a seizure-free life upon treatment with antiepileptic drugs (AEDs). Unfortunately, seizures in up to 30% do not respond to treatment. It is estimated that 90% of people with epilepsy live in developing countries, and most of them receive no drug treatment for the disease. This treatment gap has motivated investigations into the effects of plants that have been used by traditional healers all over the world to treat seizures. Extracts of hundreds of plants have been shown to exhibit anticonvulsant activity in phenotypic screens performed in experimental animals. Some of those extracts appear to exhibit anticonvulsant efficacy similar to that of synthetic AEDs. Dozens of plant-derived chemical compounds have similarly been shown to act as anticonvulsants in various in vivo and in vitro assays. To a significant degree, anticonvulsant effects of plant extracts can be attributed to widely distributed flavonoids, (furano)coumarins, phenylpropanoids, and terpenoids. Flavonoids and coumarins have been shown to interact with the benzodiazepine site of the GABAA receptor and various voltage-gated ion channels, which are targets of synthetic AEDs. Modulation of the activity of ligand-gated and voltage-gated ion channels provides an explanatory basis of the anticonvulsant effects of plant secondary metabolites. Many complex extracts and single plant-derived compounds exhibit antiinflammatory, neuroprotective, and cognition-enhancing activities that may be beneficial in the treatment of epilepsy. Thus, botanicals provide a base for target-oriented antiepileptic drug discovery and development. In the future, preclinical work should focus on the characterization of the effects of plant extracts and plant-derived compounds on well-defined targets rather than on phenotypic screening using in vivo animal models of acute seizures. At the same time, available data provide ample justification for clinical studies with selected standardized botanical extracts and plant-derived compounds. This article is part of a Special Issue entitled "Botanicals for Epilepsy"., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Ingredients of commercial herbal medicines are assessed for quality primarily to ensure their safety. However, as complex mixtures of different groups of plant secondary metabolites, retention of overall phytochemical consistency of herbal medicines is pivotal to their efficacy. Authenticity and homogeneity of the herbs and strict regimes of physical processing and extract manufacturing are critical factors to maintain phytochemical consistency in commercial products. To ensure both safety and efficacy of herbal medicines, implementation of and adherence to good agricultural and collection practice (GACP), good plant authentication and identification practice (GPAIP), good manufacturing practice (GMP) before and during the manufacturing process, and good laboratory practice (GLP) in analysis are necessary. Establishment and application of harmonized multilaboratory-validated analytical methods and transparency in the supply (value) chain through vendor audits are additional requirements in quality assurance. In this article, we outline steps of a comprehensive quality assurance paradigm aimed at achieving and maintaining safety, consistent phytochemical composition, and clinical efficacy of ingredients of herbal medicines. This article is part of a Special Issue entitled Botanicals for Epilepsy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Traditional Chinese herbal medicine is the most widely practiced form of herbalism worldwide. It is based on a sophisticated system of medical theory and practice that is distinctly different from orthodox Western scientific medicine. Most traditional therapeutic formulations consist of a combination of several drugs. The combination of multiple drugs is thought to maximize therapeutic efficacy by facilitating synergistic actions and ameliorating or preventing potential adverse effects while at the same time aiming at multiple targets. Orthodox drug therapy has been subject to critical analysis by the "evidence-based medicine" movement, and demands have been made that herbal medicine should be subject to the same kind of scrutiny. However, evaluation of the effectiveness of herbal medicines can be challenging, as their active components are often not known. Accordingly, it may be difficult to ensure that an herbal preparation used in clinical trials contains the components underlying its purported therapeutic effect. We reasoned that the identification of actions of herbal medicines at well-defined molecular targets and subsequent identification of chemical compounds underlying these molecular effects might serve as surrogate markers in the hypothesis-guided evaluation of their therapeutic efficacy. A research program was initiated to characterize in vitro molecular actions of a collection of 58 traditional Chinese drugs that are often used for the treatment of stroke. The results indicate that these drugs possess activity at disparate molecular targets in the signaling pathways involved in N-methyl-d-aspartate (NMDA) receptor-mediated neuronal injury and death. Each herbal drug contains diverse families of chemical compounds, where each family comprises structurally related members that act with low affinity at multiple molecular targets. The data appear to support the multicomponent, multitarget approach of traditional Chinese medicine. Glutamate release and excessive stimulation of NMDA receptors cause status epilepticus-induced neuronal death and are involved in epileptogenesis. Therefore, these results are also relevant to the development of antiepileptogenic and neuroprotective therapy for seizures. The combination of principles of modern molecular medicine with certain ideas of traditional empirical Chinese medicine may be beneficial in translational medicine in general.