Study Identifies the Future Development of Compounds with Potential Activitiy Against Therapy-Resistant Epilepsy
In patients with epilepsy, normal neurological activity becomes disrupted, causing debilitating seizures. Earlier this year, researchers reported in the American Chemical Society Chemical Neuroscience journal that they have found a potential new treatment for this disorder in traditional Chinese medicine (TCM).
Tests of extracts from plants used in these ancient remedies led the team to one compound derived from a magnolia tree that quelled drug-resistant seizures in both fish and mice.
Epilepsy is one of the most common neurological diseases worldwide, and the World Health Organization estimates that about 50 million people have the disorder. Medications are available, but they don’t help everyone. Research suggests that about 70 percent of patients with epilepsy can control it well with medication, leaving many patients without effective treatment. Even when they work, the drugs can cause a range of side effects, from dizziness to mood disruptions. To look for new drug leads that could help even those patients who don’t respond to conventional anti-seizure medications, Peter de Witte and his colleagues set their sights on plants used in traditional Chinese medicine.
The team collected 14 plants used in traditional Chinese medicine anti-seizure remedies. They then tested the plants’ extracts in two types of zebrafish with epileptic-like seizures, one of which could respond to conventional anti-seizure medications; the other type could not. Only the ethanol and acetone extracts from the bark of Magnolia officinalis, a tree native to China, reduced seizure-like behaviour in both types of fish. This ethylketopentenoate (EKP) model is considered as a discovery platform to find mechanistically novel antiseizure drugs, as it responds poorly to many anti-epileptics on the market.
Researchers showed that magnolol and honokiol, two major constituents of M. officinalis, displayed an effective behavioural and electrophysiological antiseizure activity in both the pentylenetetrazole (PTZ) and the EKP models. Out of six structural analogues tested, only 4-O-methylhonokiol was active.
In tests with mice, the researchers found that the magnolia bark’s most potent anti-seizure compound, magnolol, reduced the rodents’ otherwise drug-resistant seizures. According to the researchers, magnolol and similar compounds in magnolia bark could provide a starting point for the development of treatments for resistant epilepsy.
Using a combination of zebrafish- and mouse-based assays, screening extracts of single plants taken together in TCM allowed researchers to identify allyl biphenol as a chemical scaffold for the future development of compounds with potential activity against therapy-resistant epilepsies.
Read the original release from the ACS here.
This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. We advise readers to always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition.