A pharmacological basis of herbal medicines for epilepsy

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 GABA_A 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”.     

Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy

Brain areas damaged by stroke and seizures express high levels of the 27-kd heat shock protein (HSP72). Whether HSP72 represents merely a marker of stress or plays a role in improving neuron survival in these cases has been debated. Some induced tolerance experiments have provided correlative evidence for a neuroprotective effect, and others have documented neuroprotection in the absence of HSP72 synthesis. We report that gene transfer therapy with defective herpes simplex virus vectors overexpressing hsp 72 improves neuron survival against focal cerebral ischemia and systemic kainic acid administration. HSP72 overexpression improved striatal neuron survival from 62.3 to 95.4% in rats subjected to 1 hour of middle cerebral artery occlusion, and improved survival of hippocampal dentate gyrus neurons after systemic kainic acid administration, from 21.9 to 64.4%. We conclude that HSP72 may participate in processes that enhance neuron survival during transient focal cerebral ischemia and excitotoxin-induced seizures.     

Molecular mechanisms of NMDA receptor-mediated excitotoxicity:implications for neuroprotective therapeutics for stroke

正Excitotoxicity is a process observed in many disease states by which an excessive synaptic excitation causes neuronal death,and is thought to be triggered by the extracellular accumulation of the excitatory neurotransmitter glutamate,which binds and activates ionotropic N-methyl-D-aspartate glutamatergic receptors(NMDARs)in the brain.Normally,NMDARs mediate calcium entry into the cell to regulate physiological processes such as synaptic plasticity and memory,     

A meta-analysis of Chinese herbal medicines for vascular dementia

OBJECTIVE: To investigate the efficacy and safety of Chinese herbal medicines in the treatment of patients with vascular dementia. DATA RETRIEVAL: We retrieved publications from Cochrane Library (2004 to July 2011), PubMed (1966 to July 2011), the Chinese Science and Technique Journals Database (1977 to July 2011), the China National Knowledge Infrastructure (1979 to July 2011), Google Scholar (July 2011), and the Chinese Biomedical Database (1977 to July 2011) using the"Chinese medicine OR Chinese herbal medicine" and "vascular dementia OR mild cognition impair OR multi-infarct dementia OR small-vessel dementia OR strategic infarct dementia OR hypoperfusion dementia OR hemorrhagic dementia OR hereditary vascular dementia". SELECTION CRITERIA: Randomized controlled trials comparing Chinese herbal medicines with placebo/western medicine in the treatment of patients with vascular dementia were included. Diagnostic standards included Diagnostic and Statistical Manual of Mental Disorders-IV, and National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l’Enseignement en Neurosciences. Two participants independently conducted literature screening, quality evaluation and data extraction. The quality of each trial was assessed according to the Cochrane Reviewers’ Handbook 5.0. MAIN OUTCOME MEASURES: Effective rate, Mini-Mental State Examination scores, Hasegawa Dementia Scale scores, and incidence of adverse reactions. RESULTS: We identified 1 143 articles discussing the effects of Chinese medicine on vascular dementia. Thirty-one of these were included in the analysis. These studies involved a total of 2 868 participants (1 605 patients took Chinese medicine decoctions (treatment group); 1 263 patients took western medicine or placebo). The results of our meta-analysis revealed that Chinese herbal remedies in the treatment group were more efficacious than the control intervention (relative risk (RR)=1.27; 95% confidence interval (CI): 1.18-1.38, P<0.01). Mini-Mental State Examination scores were higher in patients taking Chinese herbal medicines than in those in the control group (weighted mean difference (WMD)=2.83; 95%CI: 2.55-3.12, P<0.01). Patients in the treatment group showed better disease amelioration than those in the control group (Hasegawa Dementia Scale scores; WMD=2.41, 95%CI: 1.48-3.34, P<0.01). There were also considerably fewer adverse reactions among those in the treatment group compared with those in the control group (RR=0.20, 95%CI: 0.08-0.47, P<0.01). CONCLUSION: Chinese herbal medicine appears to be safer and more effective than control measures in the treatment of vascular dementia. However, the included trials were generally low in quality. More well-designed, high-quality trials are needed to provide better evidence for the assessment of the efficacy and safety of Chinese medicines for vascular dementia.     

中成药对缺血性脑血管病二级预防疗效随访观察

目的 探讨中成药对缺血性脑血管病二级预防的疗效.方法 2008-12～2009-08在潍坊市脑科医院神经内科门诊及住院诊断为缺血性脑血管病的患者,其中服用阿司匹林127例作为对照组,在常规服用阿司匹林基础上加用中成药119例作为治疗组,电话及门诊随访6~12个月,比较2组患者脑梗死复发率.结果 治疗组的复发率为10.9...     

The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis

Autoreactive T cells are a component of the normal immune system. It has been proposed that some of these autoreactive T cells even have a protective function. Recent studies support this notion by demonstrating that (a) myelin basic-protein (MBP-) specific T cells show neuroprotective effects in vivo, and (b) activated antigen-specific human T cells and other immune cells produce bioactive brain-derived neurotrophic factor (BDNF) in vitro. Furthermore, BDNF is expressed in different types of inflammatory cells in brain lesions of patients with acute disseminated leukoencephalopathy or multiple sclerosis. We postulate that the neuroprotective effect of T cells and other immune cells observed in vivo is at least partially mediated by BDNF and other neurotrophic factors. The concept of neuroprotective autoimmunity has obvious implications for the therapy of multiple sclerosis and other neuroimmunological diseases.     

The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis

Neurological Sciences - Autoreactive T cells are a regular component of the healthy immune system. It has been proposed that some of these autoreactive T cells even might have a protective...     

KCNQ2/KCNQ3 K+ channels and the molecular pathogenesis of epilepsy: implications for therapy

In 1998, the discovery of two novel genes KCNQ2 and KCNQ3, mutated in a rare inherited form of epilepsy known as benign familial neonatal convulsions, for the first time enabled insight into the molecular etiology of a human idiopathic generalized epilepsy syndrome. These disease genes encode subunits of neuronal M-type K+ channels, key regulators of brain excitability. Analogies between benign familial neonatal convulsions and other channelopathies of skeletal and cardiac muscle, including periodic paralysis, myotonia and the long QT syndrome, provide clues about the nature of epilepsy-susceptibility genes and about the fundamental basis of epilepsy as an episodic disorder. It now appears that the KCNQ2/KCNQ3 K+ channels that are mutated in benign familial neonatal convulsions represent an important new target for anti-epileptic drugs. In the future, the identification of ion channel defects as predisposing factors in the common epilepsies could herald a new era of genotype-specific therapies.     

A review of herbal medicines for psychiatric disorders

OBJECTIVE: This review examines herbs commonly used for psychiatric symptoms-St. John's wort, kava, ginkgo biloba, and valerian. METHODS: MEDLINE was searched for articles related to the use of herbs in psychiatry published after 1990. A secondary search examined sources cited in articles obtained from the MEDLINE search. RESULTS: Of nine controlled and standardized trials of St. John's wort, five showed the herb's superiority to placebo, and four found no differences in effectiveness when compared with antidepressant drugs. The pharmacologically active components are not known. Several double-blind, placebo-controlled trials have demonstrated the anxiolytic efficacy of kava, but these studies had ill-defined patient populations, small sample sizes, and short treatment duration. All but one of 40 controlled trials of ginkgo extracts in the treatment of dementia found clinically significant improvement in memory loss, concentration, fatigue, anxiety, and depressed mood. Most studies of gingko had poorly defined patient populations and small sample sizes and used nonstandard measures. A recent well-designed multicenter study showed significantly less decline in cognitive function among patients with dementia receiving gingko. Valerian has been shown to decrease sleep latency and nocturnal awakenings and improve subjective sleep quality, but placebo effects were marked in some studies, and in some cases the beneficial effects were not seen until two to four weeks of therapy. CONCLUSIONS: Although evidence of the efficacy of herbal preparations in treating psychiatric conditions is growing, translating the results of efficacy studies into effective treatments for patients is hampered by the chemical complexity of the products, the lack of standardization of commonly available preparations, and the paucity of well-controlled studies.     

电针及灸法结合计算机虚拟辅助系统对脑卒中后痉挛性偏瘫的 临床效果

目的 观察中医电针及灸法结合计算机虚拟辅助康复系统治疗卒中后痉挛型偏瘫患者的 临床疗效。方法 选取2015年3月—2016年3月四川省八一康复中心收治的卒中后肌张力障碍患者90例, 采用随机数字表法将其分组。其中,试验A组30例,采用电针及灸法结合计算机虚拟辅助系统;试验B组 30例,采用传统运动治疗结合中医电针及灸法;试验C组30例,采用计算机虚拟辅助系统结合运动治疗。 以移动能力评定、改良Barthel指数、肌张力评定来评价疗效。结果 试验A组患者在肌张力改善程度（改 良Ashworth）、日常生活能力（改良Barthel指数）及移动能力评分（FIM）3个量表的评定中均优于B组及C组; 同时,B 组在以上量表的评定中优于C 组;且各组组间差异均有统计学意义（P＜ 0.05）。结论 电针及灸 法结合计算机虚拟辅助康复系统对卒中后偏瘫患者的单侧痉挛情况的康复具有明显的改善。     

Insights into the molecular pathogenesis of progression in multiple sclerosis: potential implications for future therapies

Despite recent advances in the diagnosis and treatment of multiple sclerosis, we still lack a consensus regarding the causes, pathogenesis, and mechanisms of disease progression. Current evidence indicates that multiple sclerosis is an inflammatory neurodegenerative disorder in which both adaptive and innate immunity play important roles in initiation and maintenance of the disease. Recent evidence supports the notion of molecular pathologic abnormalities beyond the plaques and dysfunction of neurons in normal appearing areas, in addition to the multifocal demyelination and axonal loss, as important features that may underlie early reversible changes in the disease. Chronic failure of remyelination, axonal regeneration, and neuronal dysfunction may contribute to disease progression. This article discusses the emerging molecular evidence for the progression of multiple sclerosis with particular focus on alterations in the local central nervous system microenvironment of neural and glial cells. The molecular pathways leading to structural and functional neurodegeneration and those that prevent regeneration need to be identified in order to design new therapeutic strategies that can halt or even reverse disease progression.     

Toward wisdom from failure: lessons from neuroprotective stroke trials and new therapeutic directions

BACKGROUND: Neuroprotective drugs for acute stroke have appeared to work in animals, only to fail when tested in humans. With the failure of so many clinical trials, the future of neuroprotective drug development is in jeopardy. Current hypotheses and methodologies must continue to be reevaluated, and new strategies need to be explored. Summary of Review- In part 1, we review key challenges and complexities in translational stroke research by focusing on the "disconnect" in the way that neuroprotective agents have traditionally been assessed in clinical trials compared with animal models. In preclinical studies, determination of neuroprotection has relied heavily on assessment of infarct volume measurements (instead of functional outcomes), short-term (instead of long-term) end points, transient (instead of permanent) ischemia models, short (instead of extended) time windows for drug administration, and protection of cerebral gray matter (instead of both gray and white matter). Clinical trials have often been limited by inappropriately long time windows, insufficient statistical power, insensitive outcome measures, inclusion of protocol violators, failure to target specific stroke subtypes, and failure to target the ischemic penumbra. In part 2, we explore new concepts in ischemic pathophysiology that should encourage us also to think beyond the hyperacute phase of ischemia and consider the design of trials that use multiagent therapy and exploit the capacity of the brain for neuroplasticity and repair. CONCLUSIONS: By recognizing the strengths and limitations of animal models of stroke and the shortcomings of previous clinical trials, we hope to move translational research forward for the development of new therapies for the acute and subacute stages after stroke.