Celery seed derivative shows promise as neuroprotectant in acute ischaemic stroke

Credit: Howard Cheng

Ischaemic stroke patients treated with a clot-busting medication and/or mechanical thrombectomy who also received butylphthalide—a novel medication initially compounded from celery seed—experienced milder neurological symptoms with better functioning at three months post-stroke, as compared to stroke patients who had their clots treated but received a placebo medication.

That is according to preliminary research presented at the International Stroke Conference (ISC; 8–10 February 2023, Dallas, USA).

In previous studies in China, butylphthalide has shown the potential to safely protect and preserve the brain from possible damage related to stroke in animal models with ischaemic stroke. The current study evaluated whether treatment with this medication may improve the outcomes of people who initially received a ‘clot-busting’ intravenous tissue plasminogen activator (IV-tPA), and/or a thrombectomy procedure to physically remove the clot, plus butylphthalide.

In China, butylphthalide is licensed for use in treating ischaemic stroke. However, it is not currently approved by the US Food and Drug Administration (FDA).

“This is the first trial to show the benefit of using a medication that protects the brain from damage caused by a lack of oxygen to brain tissue,” said Baixue Jia (Capital Medical University/China National Clinical Research Center for Neurological Diseases, Beijing, China), co-author of the study. “The medication was given to patients with acute ischaemic stroke who were also receiving treatment to restore blood flow to the brain.”

The researchers studied 90-day outcomes in 1,216 adults (average age=66 years, 68% men) after they suffered a stroke that was initially treated with tPA or mechanical clot removal. The participants were treated between 2018 and 2022 at one of 59 medical centres in China. People who had minimal stroke symptoms on their initial exam, defined as 0–3 on the National Institutes of Health Stroke Scale (NIHSS), or had severe stroke symptoms (defined as >26 on NIHSS) were excluded from this study.

Along with their physician-selected initial treatment, participants were randomised to receive either butylphthalide or a lookalike placebo administered by daily intravenous injection for the first 14 days, followed by 76 days of oral capsules. The patients were randomly assigned to the butylphthalide treatment group (607 adults) or the placebo group (609 adults). Neither the patients nor the research team knew which participants were assigned to which treatment.

Outcomes were deemed favourable if an individual had the following markers at 90 days post-stroke: an initially mild-to-moderate stroke (4–7 on NIHSS) and had no symptoms (0 on the modified Rankin Scale [mRS]) after treatment; an initially moderate-to-serious stroke (8–14 on NIHSS), and had no residual symptoms or mild symptoms that did not impair their ability to perform routine activities of daily living without assistance (0–1 on mRS); or an initially serious-to-severe stroke (15–25 on NIHSS) and had no remaining symptoms or a slight disability that impaired some activities yet still allowed a person to conduct their own affairs without assistance (0–2 on mRS).

The study found that:

  • Participants in the butylphthalide group were 70% more likely to have a favourable 90-day outcome compared to the placebo group
  • Butylphthalide improved function equally well in the subsets of patients who initially received tPA, those who received thrombectomy, and those who received both tPA and thrombectomy
  • Secondary events, such as recurrent stroke and intracranial haemorrhage, were not significantly different between the butylphthalide and placebo groups

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post-stroke compared to those who received the placebo,” Jia added. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

How butylphthalide works is not currently clear, according to the researchers, with animal studies suggesting various possible mechanisms. And, Jia also noted, the “next step” should be investigating the exact mechanisms of butylphthalide in humans.

The current study is limited by being based on participants who all received initial treatment with intravenous, clot-busting medications, or a thrombectomy procedure—or both—meaning the results may not be generalisable to stroke patients who received other treatments. In addition, results from this trial conducted in China may not be generalisable to other populations.

“While these are interesting results, this is only one relatively small study on a fairly select population in China,” commented American Stroke Association (ASA) volunteer expert Daniel Lackland (Medical University of South Carolina, Charleston, USA), who was not involved in the study. “Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment; however, these results warrant further study consideration. The medication used in this study is not the same as celery seed or celery seed extract supplements. Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”


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