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Safety Profile of MLC601 (Neuroaid (R)) in Acute Ischemic Stroke Patients: A Singaporean Substudy of the Chinese Medicine Neuroaid Efficacy on Stroke Recovery Study
Abstract and Figures
Previous clinical trials have shown that Neuroaid (MLC601), a traditional Chinese medicine, shows good tolerability and superiority over another traditional Chinese medicine in terms of neurological disability and functional outcome and thus may be beneficial as part of a poststroke rehabilitation program. The safety of MLC601 on hemostasis, hematology and biochemistry has been established in normal subjects and patients with nonacute stroke over a short treatment period. We assessed the safety of Neuroaid in patients with acute stroke treated for 3 months in a substudy of an ongoing randomized placebo-controlled trial.
Laboratory tests (biochemical, hematological and electrocardiogram) were conducted at the month 3 follow-up, in addition to baseline tests. A total of 114 patients were recruited. As there were 13 dropouts, a total of 52 patients on MLC601 and 49 on placebo were available for analysis. Serious adverse events (SAEs) were also analyzed.
There were no statistically or clinically significant differences between treatment groups in biochemical, hematological or electrocardiogram tests at month 3, nor any statistically or clinically significant differences in the absolute and relative changes of the various parameters between baseline and 3 months. SAEs were similar and were those commonly seen in stroke patients.
Longer-term laboratory safety data show no differences between MLC601 and placebo, confirming the safety of MLC601 in acute stroke patients receiving a 3-month treatment.
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... Many drugs have been evaluated in clinical trials; however, the majority of NMDA receptor antagonists have failed to exert good efficacy and a good safety profile for the treatment of epilepsy. NeuroAid (MLC 901; Moleac Pte Ltd., Singapore) is a Chinese herbal medicine that is widely used in the treatment of stroke in Asia [9]. In vitro and in vivo results show that NeuroAid makes cells more resistant to glutamate toxicity, increases neurite outgrowth and connectivity, and reduces infarct volume [10]. ...
... Excessive glutamatergic neurotransmission is considered one of the underlying factors of EP [26]. These findings are augmented by previous in vitro and in vivo results, which have demonstrated the ability of NeuroAid to potentiate neuronal cells and prevent glutamate toxicity [9]. ...
NeuroAid II, a folk Chinese Medicine, is currently used in Asia for the treatment of stroke.An experimental study demonstrated that NeuroAid enables neuronal cells to be more resistantto glutamate toxicity. This research was constructed to evaluate the efficacy of NeuroAid in theprevention of epilepsy (EP). Forty healthy adult male mice were used and divided into four groups(10 mice/group): normal control group; positive control group; NeuroAid-treated group (10 mg/kg);topiramate-treated group (10 mg/kg). The treatment continued for 7 days, and on the last day, EPwas induced using strychnine at a dose of 2 mg/kg via intraperitoneal (ip) administration. Seizureseverity, latency to the seizure onset, the number of seizures, and the duration of each seizure episodewere observed for one hour. The death and protection rates over the next twenty-four hours wererecorded. Brain specimens from surviving animals were extracted and examined pathologically forquantification of glutamate receptor (GluR) gene expression in the isolated hippocampus employingreal-time PCR analysis. Treatment with NeuroAid resulted in a significant reduction in seizureseverity, prolonged the onset of seizures, decreased the number and duration of episodes, reducedbrain insult, and decreased mortality rate. Reductions in the gene expression of GluRs in thehippocampus with minor histopathological changes were observed in the NeruoAid- and topiramate-treated groups. It is concluded that NeuroAid has a potential antiepileptic effect (EP) with the abilityto prevent convulsion through its effect on the glutamate receptor.
(PDF) Antiepileptic Effect of Neuroaid® on Strychnine-Induced Convulsions in Mice. Available from: https://www.researchgate.net/publication/365792514_Antiepileptic_Effect_of_NeuroaidR_on_Strychnine-Induced_Convulsions_in_Mice [accessed Jan 29 2023].
... 5 Moleac (MLC) 901 is a traditional Chinese medication approved by the Sino Food and Drug Administration in 2001 and used widely as a treatment for post-stroke patients to improve neurological function in China, especially in the nonacute phase. 6,7 MLC901 is a simplified version of a previous form, MLC601, which contains 9 herbal components, namely Radix Astragali, Radix Salviae Miltorrhizae, Radix Paeoniae Rubra, Rhizoma Chuanxiong, Radix Angelicae Sinensis, Carthamus Tinctorius, Prunus Persica, Radix Polygalae, and Rhizoma Acori Tatarinowii. 5 The traditional Chinese medicine added to the MLC901 capsule has the effect of Qi restoration and blood circulation improvement after ischemic stroke based on traditional Chinese medication theory. ...
... MLC901 is known to be widely used as a treatment for post-stroke patients to improve neurological function, especially in the non-acute phase in China. 6,7 Studies have shown that MLC901, the active component of the drug NeuroAiD II ® , improves recovery in the acute and recovery phases of stroke. It is also considered to be safe and well-tolerated, and it can reduce early vascular events since it has been shown not to modify hemostasis, hematology, and biochemistry properties in normal subjects and stroke patients. ...
Introduction
Moleac (MLC) 901 is a traditional Chinese medication approved by the Sino Food and Drug Administration in 2001 for treating stroke. This study aims to analyze the efficacy of MLC901 in animal stroke models after medial cerebral artery occlusion (MCAO).
Methods
Literature selection was performed according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) 2015. Inclusion criteria for the experimental studies were the use of animal models, publication in English between 1990 and 2020, information regarding the intervention technique used, and outcomes regarding the efficacy of MLC901 administration.
Results
MLC901 administration resulted in significantly less infarction volume by a mean difference of 17.17 compared to the control group (p < .00001). The MLC901 group resulted in significant improvement in 5-bromo-20-deoxyuridine (BrdU)-positive cells expression by a mean difference of 662.79 (p < .00001) and neurological function, which was indicated by a mean difference in the Bederson Neurological Outcome Score of 1.40 (p < .00001).
Conclusions
MLC901 administration in an animal stroke model resulted in a better reduction in infarction volume and improvement in BrdU expression and neurologic function. These data could help in further determining the efficacy of MLC901 for acute ischemic brain injury in humans.
... have also shown in vivo pharmacological efficiency consisting in the prevention of neuronal death, lowering infarct size, facilitation of post-stroke recovery and stimulation of neurogenesis (Heurteaux et al., 2010. Clinical studies confirmed the safe profile of NeuroAiD in the long-term use (Young et al., 2010), and efficiency of 3-months MLC601 treatment embodying in achievement of better functional independence at long duration Page 89 of 211 points of 6 months persisting up to 18 months after stroke (Venketasubramanian et al., 2015). ...
An enormous percentage of acute and chronic disorders at the systemic and central levels is underlined by an excessive or non-resolving inflammatory response of the immune system contributing to disease development. Ischemic stroke is undoubtedly one of the worst devastating disorders worldwide where neuroinflammation characterized by microglial activation and production of proinflammatory mediators plays a crucial role in stroke pathobiology worsening its outcome. This thesis deals with the anti-inflammatory potential of natural stilbenes and their ability to intervene in toll-like receptor 4 (TLR4)-mediated activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) pathways. Several of 37 tested stilbenes displayed the ability to remarkably reduce the expression of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), dampen up-stream the NF-κB/AP-1 activity, as well as the activation of mitogen-activated protein kinases (MAPKs) or inhibitor κB-alpha (IκBα) degradation in THP-1 macrophages and THP-1-XblueTM-MD2-CD14 monocytes. The first part of this thesis demonstrates the potent in vitro anti-inflammatory effects of stilbenes found in food and medicinal plants, eventually applicable to the prevention of systemic inflammatory disorders. Simultaneously, this pharmacological screening led to the identification of compounds with the most promising anti-inflammatory potential, among them, macasiamenene F (MF), very low investigated prenylated stilbene from Macaranga siamensis. MF anti-inflammatory potential was next studied at the central nervous system (CNS) level, on the model of lipopolysaccharide (LPS)-stimulated BV-2 cells and brain-sorted mouse microglia. MF showed the ability to reduce inflammation at whatever stage of treatment. MF used in pre-treatment radically down-regulated the gene and protein expression of TNF-α and IL-1β. Additionally, MF showed the cytoprotective effects against LPS-induced loss of microglia. When applied as co- and post-treatment, MF was able to inhibit the ongoing inflammation, which indicates its potential usefulness also in acute brain disorders, such as cerebral ischemia. Therefore, the ability of MF to counteract other deleterious mechanisms of the ischemic cascade, such as oxidative stress and glutamate-induced excitotoxicity, was further investigated. Although the antioxidant action of MF was determined as poor, MF exerted the capability to protect primary cortical neurons against N-methyl-D-aspartate (NMDA)-induced excitotoxic damage. To evaluate the ability of MF to antagonize the ischemic conditions, MF-treated cortical neurons were exposed to 1 h/2 h Oxygen Glucose Deprivation (OGD)-challenge (OGD model). Then, MF was formulated into liposomes for the purpose of improving its water solubility and further testing in vivo on the model of middle cerebral artery occlusion (MCAo).
... However, more recently, in vitro and in vivo studies have shown that NeuroAid II is able to potentially reverse ischemic tissues in the brain and promote neurogenesis [13][14][15]. Although multiple studies have proved its efficacy and long-term safety profile [16][17][18], these studies excluded patients who had concomitant anticoagulation onboard [19][20][21]. As NeuroAid II consist of herbal contents, its use is licensed as Food Supplements as opposed to Drugs in many Asian countries; including Malaysia. ...
Background
NeuroAid II (MLC901) is a promising therapy for stroke patients who present outside of therapeutic window for reperfusion therapy. Studies have proven its efficacy in ischemic stroke; however, data of drug safety and combination with other medications especially anticoagulants are heterogenous. We report a possible case of hepatotoxicity induced by NeuroAid II in combination with anticoagulants.
Case presentation
We report an elderly patient who developed symptoms of cardioembolic stroke presented outside of time window for reperfusion therapy. He was started on a regiment of statins, anticoagulation, beta blockers and NeuroAid II. One month later he presented with deranged liver enzymes. Cessation of NeuroAid II resulted in rapid improvement of transaminitis within days.
Conclusions
We wish to highlight the potential harmful effect of administering NeuroAid II with an anticoagulant and the importance of routine follow-up and blood monitoring in the elderly patients with stroke.
... Over the next few years, many studies have reported on the benefits of MLC601, including a double-blind, placebocontrolled pilot study to investigate the potential efficacy of MLC601 in enhancing post-stroke recovery, which indicated that some positive trends were observed in the MLC601 group, and thus it may be useful for post-stroke rehabilitation [3,4,8,9]. With regards to its safety profile, long-term laboratory data (biochemical, haematological, or electrocardiogram tests) confirms safety of MLC601 in acute stroke patients receiving a 3-month treatment, with no risk of increased haemorrhage [10,11]. Currently, Neuroaid II (MLC901), a simplified version of MLC601 which contains solely herbal components, has been made available. ...
Stroke is a leading cause of death and disability. NeuroAid (MLC601), which originates from Traditional Chinese Medicine, comprises herbal and animal components, and has been shown to improve the functional status of patients after ischaemic stroke. The use of NeuroAid II (MLC901), which comprises only the herbal components of MLC601, in haemorrhagic stroke has not been previously reported. Our patient is a 63-year-old male with a significant stroke risk factor of hypertension. He developed visual field defect, aphasia, unilateral weakness, and hemisensory loss. CT scan showed a left thalamic haemorrhage. In addition to anti-hypertensive therapy and intensive rehabilitation, he was prescribed MLC901. Over a period of 6 months, he had significant improvements in his motor, sensory, and speech function. There were no adverse events, serial brain CT scans showed resolution of the haemorrhage. MLC901 may have a role in post-stroke recovery after intracranial haemorrhage.
... MLC601 has been shown to significantly attenuate neurological motor deficits, brain apoptosis, and activated microglia (e.g., microgliosis, amoeboid microglia, and microglial overexpression of TNF-α) associated with cerebral contusion caused by TBI [7]. This natural product formulation has an excellent clinical and biological safety profile [8,9]. It has been studied and used widely for post-stroke recovery, showing persistent clinical benefits and safety in a large multicenter, randomized, double-blind, placebo-controlled trial. ...
Background:
MLC601 is a natural product formulation from Chinese medicine that is extensively studied in ischemic stroke. Traumatic brain injury (TBI) shares pathophysiological mechanisms with ischemic stroke, yet there are few studies on the use of MLC601 in treating TBI. This Indonesian pilot study aimed to investigate clinical outcomes of MLC601 for TBI.
Methods:
This randomized controlled trial included subjects with nonsurgical moderate TBI allocated into two groups: with and without MLC601 over three months in addition to standard TBI treatment. Clinical outcomes were measured by the Glasgow Outcome Scale (GOS) and Barthel Index (BI) observed upon discharge and at months (M) 3 and 6.
Results:
Thirty-two subjects were included. The MLC601 group (n = 16) had higher GOS than the control group (n = 16) at all observation timepoints, though these differences were not statistically significant (p = 0.151). The BI values indicated a significant improvement for the MLC601 group compared to the control group at M3 (47.5 vs. 35.0; p = 0.014) and at M6 (67.5 vs. 57.5; p = 0.055). No adverse effects were associated with MLC601 treatment.
Conclusion:
In this cohort of nonsurgical moderate TBI subjects, MLC601 showed potential for a positive effect on clinical outcome with no adverse effects.
... No changes in cardiac, hematological, hemostatic and biochemical parameters were observed, even with coadministration of aspirin [27,28]. ...
... Aside from significantly improving functional independence at 6 to 18 months after a stroke, MLC601 has an excellent safety profile, with adverse events equivalent to placebo [21,22]. Laboratory tests performed in a subgroup of acute ischemic stroke patients during the first 3 months of treatment showed no differences in biochemistry, hematological parameters, and electrocardiogram between the MLC601-and placebo-treated groups [23]. Long-term safety up to 6 months of a 3-month regimen of MLC601 was also assessed in acute ischemic stroke in another study [24]. ...
Background
Dementia is a large and growing health care burden globally, and its major cause is Alzheimer's disease (AD). MLC901 (Neuroaid II) is a simplified form of MLC601 (Neuroaid), a Traditional Chinese Medicine with neuroprotective and neuroproliferative properties in cellular and animal models of brain injury. MLC601 has been shown to modulate amyloid precursor protein (APP) processing in human neuroblastoma cell cultures and increase the levels of soluble APPα. In addition, MLC901 has been shown to reduce tau phosphorylation in vitro. Hence, MLC901 may have possible multimodal actions and a disease-modifying effect in AD. In previous clinical studies, MLC601 has shown promising effects in AD.
Objective
To investigate the safety and efficacy of MLC901 add-on therapy to standard treatment in mild-to-moderate probable AD patients stable on standard treatment and to evaluate if MLC901 has a disease-modifying effect in AD.
Methods
This is a 6-month randomized, double-blind, placebo-controlled trial in mild-to-moderate probable AD where MLC901 will be given as an add-on therapy to standard AD treatment, followed by an extension study for another 6 months, where all subjects will be treated with open-label MLC901 in addition to standard treatment. The primary outcome is safety as measured by adverse events, vital signs, electrocardiogram, laboratory tests, and physical and neurological examinations. Secondary outcomes evaluating cognition, behavior, and activities of daily living at various time points include the Alzheimer's Disease Assessment Scale–cognitive subscale, Alzheimer's Disease Cooperative Study–Clinical Global Impression of Change, Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory, Neuropsychiatric Inventory, and Mini–Mental State Examination.
Conclusion
MLC901 has the potential to improve cognition in AD patients. It may also have a role in delaying disease progression. This study will be the first to provide safety and efficacy data for MLC901 in mild-to-moderate probable AD patients already receiving standard therapy.
Cerebral ischemia is a cerebrovascular disease with symptoms caused by insufficient blood or oxygen supply to the brain. When blood supplied is restored after cerebral ischemia, secondary brain injury may occur, which is called cerebral ischemia-reperfusion injury (CIRI). In this process, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays an important role. It mediates neuroinflammation and participates in the regulation of physiological activities, such as cell proliferation, differentiation, and apoptosis. After CIRI, M1 microglia is activated and recruited by the damaged tissue. The inflammatory factors are produced by M1 microglia through the JAK/STAT pathway, eventually leading to cell apoptosis. Meanwhile, the JAK2/STAT3 signaling pathway and the expression of lipocalin-2 and caspase-3 could increase. In the pathway, phosphorylated JAK2 and phosphorylated STAT3 function of 2 ways. They not only promote the proliferation of neurons, but also affect the differentiation direction of neural stem cells by further acting on the Notch signaling pathway. Recently, traditional Chinese medicine (TCM) is a key player in CIRI, through JAK2, STAT3, STAT1 and their phosphorylation. Therefore, the review focuses on the JAK/STAT signaling pathway and its relationship with CIRI as well as the influence of the TCM on this pathway. It is aimed at providing the basis for future clinical research on the molecular mechanism of TCM in the treatment of CIRI.
Introduction:
Traumatic brain injury (TBI) is a leading cause of death in young adults globally and 90% of cases are mild TBI. Treatment to facilitate recovery after TBI is needed. Traditional medicine MLC901 (NeuroAiD II) with neuroprotective and neuroproliferative properties in cellular and animal models of brain injury showed TBI-associated cognitive improvement in mild or moderate TBI.
Methods and analysis:
This is a randomised placebo-controlled trial, with 6-month treatment and 9-month follow-up, to determine the safety and efficacy of MLC901 in improving cognitive function in patients with cognitive impairment following mild TBI. This multicentre trial is conducted at the research centres of six hospitals/institutions in Russia. The primary outcome is to determine the effect of MLC901 on complex attention using the CNS Vital Signs (CNS-VS) online neurological test after 6-month treatment in patients receiving MLC901 compared with placebo. Secondary outcomes include other cognitive domains of CNS-VS and Rivermead Post Concussion Symptoms Questionnaire. The exploratory endpoints include Quality of Life after Brain Injury, Hospital Anxiety and Depression Scale and evaluation of improved neurological parameters 3 months after treatment completion. In addition, treatment compliance, concomitant therapies and adverse events will be collected. Investigators will use a secured online system for data entry.
Ethics and dissemination:
The study has been approved by the ethic committee of Ministry of Health of the Russian Federation (No: 58074). The results of this study will be published in a peer-review journal and presented at international conferences as poster presentations.
Trial registration number:
NCT04861688.
Rationale Traditional Chinese Medications(TCM) have been reported to have beneficial effects in stroke patients, but were not rigorously evaluated by GCP standards.
Aim This study tests the hypothesis that Neuroaid, a TCM widely used in China post-stroke, is superior to placebo in reducing neurological deficit and improving functional outcome in patients with acute cerebral infarction of an intermediate severity.
Design This is a multicenter, randomised, double-blind, placebo-controlled study of Neuroaid in ischemic stroke patients with National Institute of Health Stroke Scale(NIHSS) 6–14 treated within 48 h of stroke onset. Neuroaid or placebo is taken (4 capsules) 3 times daily for 3 months. Treatments are assigned using block randomization, stratified for centers, via a central web-randomization system. With a power of 90% and two-sided test of 5% type I error, a sample size is 874. Allowing for a drop-out rate of up to 20%, 1100 individuals should be enrolled in this study.
Study Outcomes The primary efficacy endpoint is the modified Rankin Scale(mRS) grades at 3 months. Secondary efficacy endpoints are the NIHSS score at 3 months; difference of NIHSS scores between baseline and 10 days, and between baseline and 3 months; difference of NIHSS sub-scores between baseline and 10 days, and between baseline and 3 months; mRS at 10 days, 1 month, and 3 months; Barthel index at 3 months; Mini Mental State Examination at 10 days and 3 months. Safety outcomes include complete blood count, renal and liver panels, and electrocardiogram.
Study registration: ClinicalTrials.gov identifier: NCT00554723.
Stroke is a leading cause of death and disability worldwide. Despite improvements in acute stroke treatment, many patients only make a partial or poor recovery. Therefore, there is a need for treatments that would further improve outcome. Danqi Piantang Jiaonang (DJ; NeuroAid), a traditional Chinese medicine widely used in China to improve recovery after stroke, has been compared with another traditional Chinese medicine in 2 unpublished randomized clinical trials. The results of these studies were pooled and reanalyzed to assess efficacy and safety.
Six hundred five subjects were randomized in 2 randomized double-blinded, controlled trials to receive either DJ or Buchang Naoxintong Jiaonang. Subjects were treated for 1 month. Inclusion criteria were: (1) patients with recent (from 10 days to 6 months) ischemic stroke; (2) patients satisfying Western diagnostic standards for stroke and traditional Chinese medicine standards for diagnosis of apoplexy; and (3) Diagnostic Therapeutic Effects of Apoplexy score >/=10.
The functional outcome, measured by the Comprehensive Function Score component of the Diagnostic Therapeutic Effects of Apoplexy scale, showed a statistically significant superiority of DJ over the control treatment group (relative risk, 2.4; 95% CI, 1.28 to 4.51; P=0.007). Tolerance was excellent in both groups.
The pooled analysis of 2 unpublished trials of DJ, a traditional Chinese medicine currently approved in China to improve neurological recovery after stroke, shows good tolerability and superiority of DJ over another traditional Chinese medicine also approved for stroke. A large double-blind randomized clinical trial is required to further assess the safety and efficacy of DJ.
Global and regional projections of mortality and burden of disease by cause for the years 2000, 2010, and 2030 were published by Murray and Lopez in 1996 as part of the Global Burden of Disease project. These projections, which are based on 1990 data, continue to be widely quoted, although they are substantially outdated; in particular, they substantially underestimated the spread of HIV/AIDS. To address the widespread demand for information on likely future trends in global health, and thereby to support international health policy and priority setting, we have prepared new projections of mortality and burden of disease to 2030 starting from World Health Organization estimates of mortality and burden of disease for 2002. This paper describes the methods, assumptions, input data, and results.
Relatively simple models were used to project future health trends under three scenarios-baseline, optimistic, and pessimistic-based largely on projections of economic and social development, and using the historically observed relationships of these with cause-specific mortality rates. Data inputs have been updated to take account of the greater availability of death registration data and the latest available projections for HIV/AIDS, income, human capital, tobacco smoking, body mass index, and other inputs. In all three scenarios there is a dramatic shift in the distribution of deaths from younger to older ages and from communicable, maternal, perinatal, and nutritional causes to noncommunicable disease causes. The risk of death for children younger than 5 y is projected to fall by nearly 50% in the baseline scenario between 2002 and 2030. The proportion of deaths due to noncommunicable disease is projected to rise from 59% in 2002 to 69% in 2030. Global HIV/AIDS deaths are projected to rise from 2.8 million in 2002 to 6.5 million in 2030 under the baseline scenario, which assumes coverage with antiretroviral drugs reaches 80% by 2012. Under the optimistic scenario, which also assumes increased prevention activity, HIV/AIDS deaths are projected to drop to 3.7 million in 2030. Total tobacco-attributable deaths are projected to rise from 5.4 million in 2005 to 6.4 million in 2015 and 8.3 million in 2030 under our baseline scenario. Tobacco is projected to kill 50% more people in 2015 than HIV/AIDS, and to be responsible for 10% of all deaths globally. The three leading causes of burden of disease in 2030 are projected to include HIV/AIDS, unipolar depressive disorders, and ischaemic heart disease in the baseline and pessimistic scenarios. Road traffic accidents are the fourth leading cause in the baseline scenario, and the third leading cause ahead of ischaemic heart disease in the optimistic scenario. Under the baseline scenario, HIV/AIDS becomes the leading cause of burden of disease in middle- and low-income countries by 2015.
These projections represent a set of three visions of the future for population health, based on certain explicit assumptions. Despite the wide uncertainty ranges around future projections, they enable us to appreciate better the implications for health and health policy of currently observed trends, and the likely impact of fairly certain future trends, such as the ageing of the population, the continued spread of HIV/AIDS in many regions, and the continuation of the epidemiological transition in developing countries. The results depend strongly on the assumption that future mortality trends in poor countries will have a relationship to economic and social development similar to those that have occurred in the higher-income countries.
Previous studies on Danqi Piantan Jiaonang (DPJ, NeuroAid), a traditional Chinese medicine, in stroke patients showed promising results. Our aim was to determine the safety of DPJ in normal subjects and stroke patients through a series of studies assessing its immediate and long-term effects, alone and in combination with aspirin, on hematological, hemostatic, and biochemical parameters.
We conducted 3 studies from December 2004 to May 2006. Study 1 was a case series which recruited 32 healthy volunteers who were given 2 oral doses of 4 DPJ capsules (0.4 g/capsule) 6 h apart. Study 2 was a randomized controlled trial of 22 healthy volunteers who received either 1 oral dose of aspirin 300 mg alone or a combination of 1 dose of aspirin 300 mg and 2 doses of 4 DPJ capsules taken 6 h apart. For both studies 1 and 2, hemostatic parameters (prothrombin time, activated partial thromboplastin time, fibrinogen, platelet aggregation, D-dimer) were tested at baseline, and after 2 and 8 h. Study 3 was a case series which recruited 10 patients with recent ischemic stroke (within 7 days) who were given 4 DPJ capsules taken orally 3 times a day for 1 month. Blood tests for hemostatic, hematological (complete blood count), and biochemical parameters (glucose, creatinine, alanine aminotransferase, aspartate transaminase, C-reactive protein) were performed at baseline, and after 1 and 4 weeks.
Apart from the expected changes in platelet aggregation in subjects taking aspirin, no significant differences were detected in hemostatic parameters at baseline, and 2 and 8 h after oral intake of DPJ alone or in combination with aspirin. Likewise, no significant differences were observed in hematological, hemostatic, and biochemical parameters at baseline, and after 1 and 4 weeks of oral intake of DPJ.
DPJ does not significantly modify hematological, hemostatic, and biochemical parameters in normal subjects and stroke patients.
Although stroke remains a leading cause of death and adult disability, numerous recent failures in clinical stroke trials have led to some pessimism in the field. Interestingly, NeuroAid (MLC601), a traditional medicine, particularly used in China, South East Asia and Middle East has been reported to have beneficial effects in patients, particularly in post-stroke complications. Here, we demonstrate in a rodent model of focal ischemia that NeuroAid II (MLC901) pre- and post-treatments up to 3 h after stroke improve survival, protect the brain from the ischemic injury and drastically decrease functional deficits. MLC601 and MLC901 also prevent neuronal death in an in vitro model of excitotoxicity using primary cultures of cortical neurons exposed to glutamate. In addition, MLC601/MLC901 treatments were shown to induce neurogenesis in rodent and human cells, promote cell proliferation as well as neurite outgrowth and stimulate the development of a dense axonal and dendritic network. MLC601 and MLC901 clearly represent a very interesting strategy for stroke treatment at different stages of the disease.
A large number of traditional Chinese patent medicine (TCPM) are widely used for ischemic stroke in China. The aim of this study was to systematically review the existing clinical evidence on TCPM for ischemic stroke.
We identified all TCPM that were listed in the Chinese National Essential Drug list of 2004 and those commonly used TCPM in current clinical practice for ischemic stroke. Fifty-nine TCPM were identified for further evaluation. We applied Cochrane systematic review methods. We searched for reports of randomized controlled trials and controlled clinical trials on any of the 59 TCPM for ischemic stroke comparing one TCPM with control. Primary outcomes included death or dependency at the end of follow-up (at least 3 months) and adverse events. Effects on neurological impairments were a secondary outcome.
One-hundred ninety-one trials (19,338 patients) on 22 TCPM were available and included, of which 120 were definite or possible randomized controlled trials and 71 were controlled clinical trials. The methodological quality of included trials was generally "poor." Few trials reported methods of randomization. Three trials were randomized, double blind, and placebo-controlled. Primary outcomes: one trial on Puerarin and one trial on Shenmai injection assessed death or dependency at the end of long-term follow-up (at least 3 months) and found no statistically significant difference between 2 groups. The reported adverse events including allergic reaction, headache, nausea, diarrhea, bellyache, blood pressure change, and subcutaneous ecchymosis. Most of the adverse events were not severe. Secondary outcomes: analysis of the secondary outcome, "marked improvement in neurological deficit," showed apparent benefits of about the same magnitude for all the TCPM studied. Of the 22 TCPM, 8 drugs (Milk vetch, Mailuoning, Ginkgo biloba, Ligustrazine, Danshen agents, Xuesetong, Puerarin, and Acanthopanax) had relatively more studies and patient numbers.
There was insufficient good quality evidence on the effects of TCPM in ischemic stroke on the primary outcome (death or dependency). We considered the apparent benefit on neurological impairment was as likely to be attributable to bias from poor methodology as to a real treatment effect. However, because the agents assessed appeared potentially beneficial and nontoxic, further randomized controlled trials are justified. Eight drugs could be further research priorities.