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      A narrative review on traditional Chinese medicine prescriptions and bioactive components in epilepsy treatment

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          Abstract

          Background and Objective

          In traditional Chinese medicine (TCM), natural drugs and their bioactive components have been widely used to treat epilepsy. Epilepsy is a chronic disease caused by abnormal discharge of brain neurons that leads to brain dysfunction and cognitive impairment. Several factors are involved in the mechanisms of epilepsy, and the current treatments do not seem promising. The potential efficacy of natural drugs with lower toxicity and less side effects have attracted increasing attention.

          Methods

          We used the terms, “TCM”, “traditional Chinese medicine”, “herbal”, “epilepsy”, “seizure”, and the name of each prescription and bioactive components in the review to collect papers about application of TCM in epilepsy treatment from PubMed online database and Chinese database including Chinese National Knowledge Infrastructure (CNKI), Wanfang, and Weipu.

          Key Content and Findings

          We summarized some common TCM prescriptions and related active components used for the treatment of epilepsy. Six prescriptions (Chaihu Shugan decoction, Tianma Gouteng decoction, Kangxian capsules, Taohong Siwu decoction, Liujunzi decoction, Compound Danshen dropping pills) and nine main bioactive compounds (Saikosaponin A, Rhynchophylline, Tetramethylpyrazine, Gastrodin, Baicalin and baicalein, α-Asarone, Ginsenoside, Tanshinone, Paeoniflorin) were reviewed to provide a scientific basis for the development of potential antiepileptic drugs (AEDs).

          Conclusions

          The pharmacological effects and molecular mechanisms of TCM in the treatment of epilepsy are complex, targeting several pathological aspects of epilepsy. However, the limitations of TCM, such as the lack of standardized treatments, have prevented its clinical application in epilepsy treatment. Thus, additional clinical trials are required to further evaluate the effectiveness and safety of TCM prescriptions and their bioactive components in the future.

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          Most cited references99

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          Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

          Summary Background Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding Bill & Melinda Gates Foundation.
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            Early identification of refractory epilepsy.

            More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy, but why this happens and whether it can be predicted are unknown. We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures. We prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year. Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent). Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.
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              A Review on Central Nervous System Effects of Gastrodin

              Rhizoma Gastrodiae (also known as Tian ma), the dried rhizome of Gastrodia elata Blume, is a famous Chinese herb that has been traditionally used for the treatment of headache, dizziness, spasm, epilepsy, stoke, amnesia and other disorders for centuries. Gastrodin, a phenolic glycoside, is the main bioactive constituent of Rhizoma Gastrodiae. Since identified in 1978, gastrodin has been extensively investigated on its pharmacological properties. In this article, we reviewed the central nervous system (CNS) effects of gastrodin in preclinical models of CNS disorders including epilepsy, Alzheimer's disease, Parkinson's disease, affective disorders, cerebral ischemia/reperfusion, cognitive impairment as well as the underlying mechanisms involved and, where possible, clinical data that support the pharmacological activities. The sources and pharmacokinetics of gastrodin were also reviewed here. As a result, gastrodin possesses a broad range of beneficial effects on the above-mentioned CNS diseases, and the mechanisms of actions include modulating neurotransmitters, antioxidative, anti-inflammatory, suppressing microglial activation, regulating mitochondrial cascades, up-regulating neurotrophins, etc. However, more detailed clinical trials are still in need for positioning it in the treatment of neurological disorders.
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                Author and article information

                Journal
                Ann Transl Med
                Ann Transl Med
                ATM
                Annals of Translational Medicine
                AME Publishing Company
                2305-5839
                2305-5847
                13 December 2022
                31 January 2023
                : 11
                : 2
                : 129
                Affiliations
                [1 ]Nantong University Informatization Center, Nantong University, Nantong, Co-innovation Center of Neuroregeneration, Nantong University, Nantong , China;
                [2 ]Department of Neurology, People’s Hospital of Binhai County, Yancheng , China;
                [3 ]Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong , China
                Author notes

                Contributions: (I) Conception and design: F Tao, Y Cai, H Sun; (II) Administrative support: H Sun; (III) Provision of study materials or patients: F Tao, Y Cai, H Sun; (IV) Collection and assembly of data: F Tao, Y Cai, C Deng, Z Chen, Y Shen; (V) Data analysis and interpretation: F Tao, Y Cai, H Sun; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Hualin Sun, PhD. Nantong University, 19 Qixiu Road, Nantong 226001, China. Email: sunhl@ 123456ntu.edu.cn .
                Article
                atm-11-02-129
                10.21037/atm-22-3306
                9929833
                36819494
                b9fd474c-5b59-4174-b292-06cb520f930f
                2023 Annals of Translational Medicine. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 27 June 2022
                : 06 November 2022
                Categories
                Review Article

                traditional chinese medicine (tcm),epilepsy,antiepileptic drugs (aeds),bioactive compound

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