Echinacea metabolism and drug interactions: The case for standardization of a complementary medicine.

Life Sci. 2009 May 7; Toselli F, Matthias A, Gillam EMThe herbal medicine, Echinacea, is used for treatment and prevention of upper respiratory tract infections. Among the phytochemicals found in Echinacea, the bioavailable alkylamides are thought to be the compounds responsible for its effects on the human immune system. Cytochrome P450 enzymes (P450s) appear to be the principal system responsible for the metabolism of Echinacea components and most of the main hepatic and some extrahepatic isoforms appear to be involved. Epoxide formation, N-dealkylation and hydroxylation appear to be the main metabolic pathways mediated by P450s. Interactions with P450s determine the circulating concentrations and duration of action of these phytochemicals as well as any potential interactions with other chemicals. Most research to date has focussed on the potential of Echinacea to interact with other drugs. Literature reports are equivocal and comparisons between studies are difficult as the phytochemical composition of the preparations examined is rarely assessed. Certain alkylamides containing a terminal acetylene appear to exert a time- and NADPH-dependent inhibition on the metabolism of other compounds. However as there are no industry standardization requirements, differences in the relative concentrations of individual alkylamides between preparations could alter the potential for interactions. A thorough phytochemical analysis of samples investigated is necessary in further studies so that sound conclusions can be drawn regarding the potential for interindividual variation in pharmacokinetics and therapeutic effects and interactions with other chemicals. Moreover standardization of alkylamide content may allow the exploitation of beneficial interactions between alkylamide components to enhance the therapeutic effect of this widely used complementary medicine.

New perspectives for synergy research with the "omic"-technologies.

Phytomedicine. 2009 May 8; Ulrich-Merzenich G, Panek D, Zeitler H, Wagner H, Vetter HSynergistic effects, understood as true overadditive effects, are often observed in experimental and clinical studies using phytopharmaceuticals. The introduction of the "omic"-technologies is now opening new perspectives in rationalizing these effects and making use of them in the development of a new generation of phytopharmaceuticals. This review describes possible mechanism of synergistic actions of herbal drugs by mono- and multitargeting and by the activation of signal cascades. It examins the possibilities of the standardization of single and multi component plant extracts and the prediction and assessment of the toxicity and safety of plant extracts with the support of the "omic"-technologies. It further discusses the use of phytopharmaceuticals in the context of an "individualized medicine". It makes proposals how to use the "omic"-technologies to rationalize and develop combination therapies of phytopharmaceuticals and synthetic drugs to minimize adverse reactions (ARs) or improve the therapeutic efficacy. Examples of clinical studies are given which explore already the potential of such co-medications. Modern medical therapy has acknowledged for quite some time the usefulness of combination therapies in the treatment of multifactorial diseases like cancer, cardiovascular or rheumatic diseases. The term "synergy" is rarely used in this context, the combinatory mechanisms of actions seldom completely understood and the potentially occurring adverse reactions feared. A systematic exploitation of synergy effects of phytomedical interventions alone or in combination with synthetic drugs should lead in a long term perspective to the discovery and development of more rational evidence-based interventions in the prevention and therapy of multifactorial diseases and should thereby enrich modern pharmacotherapy.

Preventive action of Kai Xin San aqueous extract on depressive-like symptoms and cognition deficit induced by chronic mild stress.

Exp Biol Med (Maywood). 2009 May 8; Dang H, Sun L, Liu X, Peng B, Wang Q, Jia W, Chen Y, Pan A, Xiao PKai Xin San (KXS), a traditional Chinese herbal medicine, has been used clinically for the treatment of depressive disorders and cognitive impairment for centuries. However, the effects of KXS on cognitive dysfunction induced by depression have not been evaluated scientifically. The present study aimed to explore the antidepressant-like and nootropic effects of an aqueous extract of KXS (at doses of 0.3, 0.9, and 2.7g/kg/day) using chronic mild stress (CMS) as a model of depression. Depressive symptoms were analyzed using the sucrose-preference and novelty-induced inhibition of feeding tests. Cognitive function was evaluated using a two-way active avoidance task. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels, acetylcholinesterase (AChE) protein expression in the hippocampus, and monoamine neurotransmitter concentrations in the prefrontal cortex and hippocampus were also determined to elucidate the neurochemical mechanisms. Expereimental results showed that KXS aqueous extract significantly ameliorated the CMS-induced depressive symptoms, including the reduced preference index and prolonged latency to novelty-suppressed feeding. Simultaneously, KXS significantly reversed the CMS-induced decrease in the numbers of active avoidance and active movement distances and increase in the numbers of the passive avoidance and passive movement distances, thereby producing nootropic effects in the two-way active avoidance test. KXS also inhibited the increased AChE expression in the hippocampus, up-regulated the decreased monoamine neurotransmitter concentrations of both brain areas and reduced the elevated ACTH concentrations in the serum induced by CMS. Taken together, these results indicate that KXS exerts its antidepressant-like and nootropic effects in the CMS model by modulating the HPA axis, monoamine neurotransmitter and cholinergic systems.