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Items 1 - 30 of 30    (Display the 30 citations in PubMed)

1. Planta Med. 2012 Sep;78(13):1458-77. doi: 10.1055/s-0032-1315117. Epub 2012 Aug 1.

Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions.

Hermann R, von Richter O.

Clinical Research Appliance, Radolfzell, Germany. robert.hermann@cr-appliance.com

Abstract

The use of herbal/botanical products, also referred to as complementary and alternative medicines (CAM), worldwide enjoys increasing popularity. It appears in particular highly prevalent in patient populations already exposed to complex treatment algorithms and polypharmacotherapy, frequently involving narrow therapeutic index drugs. Accordingly, the potential clinical dimension and relevance of herb-drug interactions has received considerable attention over the last years. However, review of pertinent literature indicates that the available clinical evidence in this regard is still limited and sometimes inconclusive. Also, communication of herb-drug interaction data in the biopharmaceutical/medical literature is often complex and confusing, not always unbiased, and in many cases appears not to strive for clear-cut and useful guidance in terms of the clinical relevance of such findings.This systematic review summarizes and interprets the published evidence on clinical herb-drug interaction studies which examined the potential of six popular herbal drugs (Echinacea, garlic, gingko, ginseng, goldenseal, and milk thistle) as perpetrators of pharmacokinetic (PK) drug interactions. Reported effect sizes were systematically categorized according to FDA drug interaction guideline criteria. A total of 66 clinical PK interaction studies, meeting the scope of the present review, were identified. The clinical evidence was found to be most robust and informative for Gingko biloba (GB; 21 studies) and milk thistle/silymarin (MT; 13), and appears still limited for ginseng (9), goldenseal/berberine (GS; 8), garlic (8), and Echinacea (7). Collectively, the available evidence indicates that, at commonly recommended doses, none of these herbs act as potent or moderate inhibitors or inducers of cytochrome P450 (CYP) enzymes or P-glycoprotein (ABCB1). Weak effects in terms of either induction or inhibition were found for GB (presystemic/hepatic CYP3A4 induction/inhibition, CYP2C19 induction at high doses), milk thistle/silymarin (CYP2C9 inhibition), GS/berberine (CYP3A4 and CYP2D6 inhibition), Echinacea (presystemic/hepatic CYP3A4 inhibition/induction, CYP1A2 and CYP2C9 inhibition at high doses). Information was found not always complete for the major drug metabolizing CYP enzymes in the less well-studied herbs and is largely limited to P-glycoprotein (ABCB1) when effects on drug transporters have been investigated.

Georg Thieme Verlag KG Stuttgart · New York.

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PMID: 22855269 [PubMed - indexed for MEDLINE]
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2. Planta Med. 2012 Sep;78(13):1428-57. doi: 10.1055/s-0031-1298536. Epub 2012 May 15.

Phenotyping studies to assess the effects of phytopharmaceuticals on in vivo activity of main human cytochrome p450 enzymes.

Zadoyan G, Fuhr U.

ITECRA GmbH & Co. KG, Cologne, Germany.

Abstract

The extensive use of herbal drugs and their multiple components and modes of action suggests that they may also cause drug interactions by changing the activity of human cytochrome P450 enzymes. The purpose of the present review is to present the available data for the top 14 herbal drug sales in the U. S. Studies describing the effects of herbal drugs on phenotyping substrates for individual CYPs were identified by a comprehensive MEDLINE search. Drugs included Allium sativum (Liliaceae), Echinacea purpurea (Asteraceae), Serenoa repens (Arecaceae), Ginkgo biloba (Ginkgoaceae), Vaccinium macrocarpon (Ericaceae), Glycine max (Fabaceae), Panax ginseng (Araliaceae), Actea racemosa (Ranunculaceae), Hypericum perforatum (Hypericaceae), Silybum marianum (Asteraceae), Camellia sinensis (Theaceae), Valeriana officinalis (Valerianaceae), Piper methysticum (Piperaceae), and Hydrastis canadensis (Ranunculaceae) preparations. We identified 70 clinical studies in 69 publications. The majority of the herbal drugs appeared to have no clear effects on most of the CYPs examined. If there was an effect, there was mild inhibition in almost all cases, as seen with garlic or kava effects on CYP2E1 and with soybean components on CYP1A2. The most pronounced effects were induction of CYP3A and other CYPs by St. John's wort and the inhibitory effect of goldenseal on CYP3A and CYP2D6, both being borderline between mild and moderate in magnitude. With the exceptions of St.John's wort and goldenseal, the information currently available suggests that concomitant intake of the herbal drugs addressed here is not a major risk for drugs that are metabolized by CYPs.

Georg Thieme Verlag KG Stuttgart · New York.

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PMID: 22588833 [PubMed - indexed for MEDLINE]
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3. Cold Spring Harb Perspect Med. 2012 Mar;2(3):a006395. doi: 10.1101/cshperspect.a006395.

Symptomatic and nonamyloid/tau based pharmacologic treatment for Alzheimer disease.

Aisen PS, Cummings J, Schneider LS.

University of California, San Diego, California 92093, USA. paisen@ucsd.edu

Abstract

In this work we consider marketed drugs for Alzheimer disease (AD) including acetylcholinesterase inhibitors (AChE-Is) and antiglutamatergic treatment involving the N-methyl-d-aspartate (NMDA) receptor. We discuss medications and substances available for use as cognitive enhancers that are not approved for AD or cognitive impairment, and other neurotransmitter-related therapies in development or currently being researched. We also review putative therapies that aim to slow disease progression by mechanisms not directly related to amyloid or tau.

PMCID: PMC3282492 Free PMC Article
PMID: 22393531 [PubMed - indexed for MEDLINE]
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4. Mol Vis. 2012;18:390-402. Epub 2012 Feb 9.

Ginkgo biloba: an adjuvant therapy for progressive normal and high tension glaucoma.

Cybulska-Heinrich AK, Mozaffarieh M, Flammer J.

Department of Ophthalmology, University of Basel, Basel, Switzerland.

Abstract

Gingko biloba has been used for hundreds of years to treat various disorders such as asthma, vertigo, fatigue and, tinnitus or circulatory problems. Two of the main extracts are EGb761 and LI 1370. Most pharmacological, toxicological and clinical studies have focused on the neuroprotective value of these two main extracts. Neuroprotection is a rapidly expanding area of research. This area is of particular interest due to the fact that it represents a new avenue of therapy for a frustrating disease that may progress despite optimal treatment. One such disease is glaucoma.Glaucoma leads to the loss of retinal ganglion cells and their axons but also to tissue remodelling which involves both the optic nerve head and the retina. In the retina the astrocytes get activated. In addition, the optic nerve gets thinner and the cells of the lateral geniculate ganglion disappear partially. On average, ocular blood flow (OBF) is reduced in glaucoma patients in various tissues of the eye. Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage. Nevertheless, there is little doubt that other risk factors besides IOP are involved. One such risk factor is a primary vascular dysregulation (PVD) occurring in patients with a disturbed autoregulation, another risk factor is oxidative stress.

PMCID: PMC3283204 Free PMC Article
PMID: 22355250 [PubMed - indexed for MEDLINE]
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5. Adv Nutr. 2011 Jan;2(1):32-50. doi: 10.3945/an.110.000117. Epub 2011 Jan 10.

Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function.

Kennedy DO, Wightman EL.

Brain, Performance and Nutrition Research Centre, School of Life Sciences, Northumbria University, Newcastle, UK. david.kennedy@northumbria.ac.uk

Abstract

Humans consume a wide range of foods, drugs, and dietary supplements that are derived from plants and which modify the functioning of the central nervous sytem (CNS). The psychoactive properties of these substances are attributable to the presence of plant secondary metabolites, chemicals that are not required for the immediate survival of the plant but which are synthesized to increase the fitness of the plant to survive by allowing it to interact with its environment, including pathogens and herbivorous and symbiotic insects. In many cases, the effects of these phytochemicals on the human CNS might be linked either to their ecological roles in the life of the plant or to molecular and biochemical similarities in the biology of plants and higher animals. This review assesses the current evidence for the efficacy of a range of readily available plant-based extracts and chemicals that may improve brain function and which have attracted sufficient research in this regard to reach a conclusion as to their potential effectiveness as nootropics. Many of these candidate phytochemicals/extracts can be grouped by the chemical nature of their potentially active secondary metabolite constituents into alkaloids (caffeine, nicotine), terpenes (ginkgo, ginseng, valerian, Melissa officinalis, sage), and phenolic compounds (curcumin, resveratrol, epigallocatechin-3-gallate, Hypericum perforatum, soy isoflavones). They are discussed in terms of how an increased understanding of the relationship between their ecological roles and CNS effects might further the field of natural, phytochemical drug discovery.

PMCID: PMC3042794 Free PMC Article
PMID: 22211188 [PubMed - indexed for MEDLINE]
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6. Rev Bras Psiquiatr. 2010 Dec;32(4):429-36.

[Medicinal plants for the treatment of generalized anxiety disorder: a review of controlled clinical studies].

[Article in Portuguese]
Faustino TT, Almeida RB, Andreatini R.

Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.

Abstract

OBJECTIVE:

This work aimed to identify controlled trials, which evaluated effectiveness of herbal medicines in subjects suffering generalized anxiety disorder.

METHOD:

Controlled studies (randomized, comparative with placebo and/or standard drug, double-blind) were sought through electronic and hand-searches. The word strategy used "plant OR phytomed* OR extract OR herbal OR medicinal (OR specific name plants)" e "anxie* OR anxioly* OR tranquil* OR GAD", limited to "human OR clinical trial OR randomized controlled trial OR meta-analysis OR review". The search was restricted to English language.

RESULTS:

Piper methysticum presented an unequivocal anxiolytic effect, but most studies also included patients with other anxiety disorders (e.g. phobias). Isolated studies with Ginkgo biloba, Galphimia glauca, Matricaria recutita, Passiflora incarnata and Valeriana officinalis showed a potential use for anxious diseases. Despite this low number of studies, Ginkgo biloba and Matricaria recutita showed an effect size (Cohen's d=0.47 to 0.87) similar or higher to standard anxiolytics drugs (benzodiazepines, buspirone and antidepressants-0.17 to 0.38). No additional study with other plants was found.

CONCLUSION:

Despite the therapeutic potential of medicinal plants in generalized anxiety disorder, very few controlled trials assessing herbal medicines in generalized anxiety disorder were found. Additionally, these studies present serious flaw design.

Free Article
PMID: 21308265 [PubMed - indexed for MEDLINE]
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7. J Alzheimers Dis. 2010;19(4):1101-22. doi: 10.3233/JAD-2010-1306.

Promoting successful cognitive aging: a comprehensive review.

Daffner KR.

Brigham Behavioral Neurology Group, Division of Cognitive and Behavioral Neurology, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. kdaffner@partners.org

Abstract

Promoting successful cognitive aging is a topic of major importance to individuals and the field of public health. This review presents a coherent framework not only for evaluating factors, protective activities, and enhancing agents that have already been proposed, but also ones that will be put forward in the future. The promotion of successful cognitive aging involves the dual goals of preventing loss of information processing capacity and cognitive reserve, and enhancing brain capacity and cognitive reserve. Four major lines of evidence are available for evaluating whether a proposed factor promotes successful cognitive aging: 1) epidemiologic/cohort studies; 2) animal/basic science studies; 3) human "proof-of-concept" studies; and 4) human intervention studies. Each line of evidence has advantages and limitations that will be discussed. Through illustrative examples, we trace the ways in which each method informs us about the potential value of several proposed factors. Currently, lines of converging evidence allow the strongest case to be made for physical and cognitively stimulating activities. Although epidemiological data seem to favor the use of statins to lower the risk of dementia, more definitive recommendations await further randomized controlled studies. There is presently no clear evidence that antioxidants or Ginkgo biloba promote successful cognitive aging. The impact of resveratrol, fish oil, and a long list of other proposed agents needs to be determined. Clinicians remain well-positioned to identify and aggressively treat vascular risk factors, diabetes, sleep disorders, and other conditions that may reduce brain capacity, and to encourage activities that can build cognitive reserve.

PMCID: PMC3047597 Free PMC Article
PMID: 20308777 [PubMed - indexed for MEDLINE]
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8. BMC Geriatr. 2010 Mar 17;10:14. doi: 10.1186/1471-2318-10-14.

Effects of Ginkgo biloba in dementia: systematic review and meta-analysis.

Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN.

Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medicine, Luisenstrasse 57, Berlin, Germany. Stefan.Weinmann@charite.de

Abstract

BACKGROUND:

The benefit of Ginkgo biloba has been discussed controversially. The aim of this review was to assess the effects of Ginkgo biloba in Alzheimer's disease as well as vascular and mixed dementia covering a variety of outcome domains.

METHODS:

We searched MEDLINE, EMBASE, the Cochrane databases, CINAHL and PsycINFO for controlled trials of ginkgo for Alzheimer's, vascular or mixed dementia. Studies had to be of a minimum of 12 weeks duration with at least ten participants per group. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as risk ratios or standardized mean differences (SMD) in scores.

RESULTS:

Nine trials using the standardized extract EGb761(R) met our inclusion criteria. Trials were of 12 to 52 weeks duration and included 2372 patients in total. In the meta-analysis, the SMDs in change scores for cognition were in favor of ginkgo compared to placebo (-0.58, 95% confidence interval [CI] -1.14; -0.01, p = 0.04), but did not show a statistically significant difference from placebo for activities in daily living (ADLs) (SMD = -0.32, 95% CI -0.66; 0.03, p = 0.08). Heterogeneity among studies was high. For the Alzheimer subgroup, the SMDs for ADLs and cognition outcomes were larger than for the whole group of dementias with statistical superiority for ginkgo also for ADL outcomes (SMD = -0.44, 95% CI -0.77; -0.12, p = 0.008). Drop-out rates and side effects did not differ between ginkgo and placebo. No consistent results were available for quality of life and neuropsychiatric symptoms, possibly due to the heterogeneity of the study populations.

CONCLUSIONS:

Ginkgo biloba appears more effective than placebo. Effect sizes were moderate, while clinical relevance is, similar to other dementia drugs, difficult to determine.

PMCID: PMC2846949 Free PMC Article
PMID: 20236541 [PubMed - indexed for MEDLINE]
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9. Am J Geriatr Pharmacother. 2009 Jun;7(3):167-85. doi: 10.1016/j.amjopharm.2009.06.003.

Drug development for Alzheimer's disease: where are we now and where are we headed?

Sabbagh MN.

The Cleo Roberts Center for Clinical Research, Banner-Sun Health Research Institute, Sun City, AZ 85351, USA. Marwan.sabbagh@bannerhealth.com

Abstract

OBJECTIVE:

The aim of this article was to provide a survey of the clinical development of pharmacotherapy for Alzheimer's disease (AD).

METHODS:

A search of PubMed to identify pertinent English-language literature was conducted using the terms Alzheimer's disease AND clinical trials (2003-2008), dementia AND prevention AND clinical trials (2003-2008), and the chemical names of all compounds mentioned in articles on new drugs for AD published since 2005. www.ClinicalTrials.gov was searched for relevant trials. Abstracts of the 2008 International Conference on Alzheimer's Disease (ICAD) were reviewed for relevance, as were pharmaceutical company and AD advocacy Web sites. Articles selected for review were primary reports of data from preclinical studies and clinical trials.

RESULTS:

A large number of drugs with differing targets and mechanisms of action are under development for the treatment of AD. Phase III trials of Ginkgo biloba, NSAIDs, phenserine, statins, tarenflurbil, tramiprosate, and xaliproden have been completed, none of them demonstrating adequate efficacy. Encouraging results from completed Phase II trials of dimebon, huperzine A, intravenous immunoglobulin, and methylthioninium chloride were reported at ICAD 2008. Nineteen compounds are currently in Phase II trials, and 3 compounds (AN1792, lecozotan SR, and SGS742) failed at this stage of development.

CONCLUSIONS:

Despite disappointing results from recently completed Phase III trials of several novel compounds, the extent and breadth of activity at all phases of clinical development suggest that new pharmacotherapeutic options for the treatment of AD will become available within the next decade.

PMCID: PMC2948028 Free PMC Article
PMID: 19616185 [PubMed - indexed for MEDLINE]
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