MLC901, a Traditional Chinese Medicine protects the brain against global ischemia

Quintard, Hervé; Borsotto, Marc; Veyssière, Julie; Gandin, Carine; Labbal, Fabien; Widmann, Catherine; Lazdunski, Michel; Heurteaux, Catherine

doi:10.1016/j.neuropharm.2011.05.003

Cited by 78 publications

(104 citation statements)

References 35 publications

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“…Consistent with observations of MLC601 efficacy in humans, pharmacological data obtained in rodents have established that MLC901 prevents death of threatened neuronal tissues, decreases cognitive deficits and improves functional outcome by restoring neuronal circuits [5,6 ](fig. 1).…”

Section: Neuroprotective Effectssupporting

confidence: 68%

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NeuroAiD: Properties for Neuroprotection and Neurorepair

et al. 2013

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Background: Treatments for stroke and other brain injuries are limited. NeuroAiD has been shown to be beneficial in clinical studies. We reviewed the pharmacological effects of NeuroAiD on the normal and ischemic brain and neurons. Methods: In vivo and in vitro experiments using mouse model of stroke (focal ischemia), rat model of cardiac arrest (global ischemia) and cortical neurons in culture were reviewed and summarized. Results: NeuroAiD improved survival, attenuated infarct size, improved functional recovery in the model of focal ischemia, and protected neurons against glutamate-induced injury. Furthermore, it enhanced cognitive recovery by reducing hippocampal CA1 cell degeneration, DNA fragmentation, Bax expression and ma-londialdehyde release in the model of global ischemia. Ac-tivation of the Akt survival pathway and opening of K_ATP channels may contribute to the neuroprotective properties of NeuroAiD. NeuroAiD increased BDNF expression and induced proliferation of cells which differentiate and mature into neurons. It enhanced rosette formation of human embryonic stem cells. NeuroAiD-treated embryonic cortical neurons developed into neurons with longer neurites, denser outgrowths and networks, and more synaptic release sites. Conclusions: NeuroAiD demonstrated both neuroprotective and neuroregenerative properties in rodent models of focal and global ischemia and in cortical cell cultures. These properties would be important for developing a treatment strategy in reducing the long-term disability of stroke, cardiac arrest and other brain injuries.

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Section: Neuroprotective Effectssupporting

confidence: 68%

“…Typical current traces recorded in control conditions (90 K) in the presence of azide (3 m M ), which mimics ischemia by reducing the intracellular ATP level, or azide + MLC901 (1 µg/ml). Some images in the figure were reproduced in part with permission from [5,6,9]. …”

Section: Neuroprotective Effectsmentioning

confidence: 99%

NeuroAiD: Properties for Neuroprotection and Neurorepair

et al. 2013

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“…6,7 MLC601 (NeuroAiD), a TCM that combines extracts of 9 herbal and 5 animal components in capsule form, has been shown to restore neurological and cellular function in animal models of ischemic stroke. [8][9][10] Initial clinical studies on patients who were 2 weeks to 6 months after index stroke showed MLC601 improved recovery in terms of functional outcome and neurological disability. 11 More studies have since been published assessing the benefit and safety of MLC601 in nonacute stroke patients using different clinical outcomes.…”

Section: August 2013mentioning

confidence: 99%

“…Furthermore, the first 3 months after stroke may offer the most significant window of opportunity for recovery of function. Given the demonstration of both neuroprotective and neuroregenerative properties in models of focal and global brain ischemia [8][9][10] and the excellent safety profile 18,19 of MLC601, it is an attractive candidate to be evaluated in acute ischemic stroke.…”

Section: August 2013mentioning

confidence: 99%

Chinese Medicine Neuroaid Efficacy on Stroke Recovery

Chen

Young²,

Gan³

et al. 2013

Stroke

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Background and Purpose— Previous clinical studies suggested benefit for poststroke recovery when MLC601 was administered between 2 weeks and 6 months of stroke onset. The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study tested the hypothesis that MLC601 is superior to placebo in acute, moderately severe ischemic stroke within a 72-hour time window. Methods— This multicenter, double-blind, placebo-controlled trial randomized 1100 patients with a National Institutes of Health Stroke Scale score 6 to 14, within 72 hours of onset, to trial medications for 3 months. The primary outcome was a shift in the modified Rankin Scale. Secondary outcomes were modified Rankin Scale dichotomy, National Institutes of Health Stroke Scale improvement, difference in National Institutes of Health Stroke Scale total and motor scores, Barthel index, and mini-mental state examination. Planned subgroup analyses were performed according to age, sex, time to first dose, baseline National Institutes of Health Stroke Scale, presence of cortical signs, and antiplatelet use. Results— The modified Rankin Scale shift analysis–adjusted odds ratio was 1.09 (95% confidence interval, 0.86–1.32). Statistical difference was not detected between the treatment groups for any of the secondary outcomes. Subgroup analyses showed no statistical heterogeneity for the primary outcome; however, a trend toward benefit in the subgroup receiving treatment beyond 48 hours from stroke onset was noted. Serious and nonserious adverse events rates were similar between the 2 groups. Conclusions— MLC601 is statistically no better than placebo in improving outcomes at 3 months when used among patients with acute ischemic stroke of intermediate severity. Longer treatment duration and follow-up of participants with treatment initiated after 48 hours may be considered in future studies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00554723.

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“…This is what has been done with NeuroAiD, a TCM compound officially registered in China in 2001 as a drug to facilitate stroke recovery at chronic stage. It has recently been shown to have potent protective effects in vitro and in vivo against focal and global ischemia in the rat and it also has a potent action to stimulate neurogenesis in vivo and in vitro [16,17]. Whether this beneficial effect will translate in humans when initiated during the acute stage within 72 h remains an open question until the results of CHIMES [1] and other large trials are available.…”

mentioning

confidence: 99%

Drugs from Natural Substances: Why Study Them in Cerebral Infarction

Bousser

2013

Cerebrovasc Dis

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MLC901, a Traditional Chinese Medicine protects the brain against global ischemia

Cited by 78 publications

References 35 publications

NeuroAiD: Properties for Neuroprotection and Neurorepair

NeuroAiD: Properties for Neuroprotection and Neurorepair

Chinese Medicine Neuroaid Efficacy on Stroke Recovery

Drugs from Natural Substances: Why Study Them in Cerebral Infarction

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