A natural product from the dried root of a pea-family plant, potentially combined with an enzyme inhibitor may provide hope in alleviating neuroinflammation in Parkinson’s disease, a team of researchers announced in Proceedings of the National of Academy of Sciences. 

The team found that a soluble epoxide hydrolase (sEH) inhibitor combined with kurarinone, a compound from the dried root of Sophora flavescens, reduced neuroinflammation in an animal model with Parkinson’s disease. The dried root, also known as kushen, has been used for hundreds of years in traditional Chinese medicines.

“Traditional Chinese medicines play an immeasurable role in the treatment of all kinds of diseases,” said lead researcher.

“We investigated the neuroprotective effects of S. flavescens in Parkinson’s disease based on the neuroinflammation,” the author said. “Our extensive studies indicated that kurarinone possesses several pharmacological effects, including anti-inflammatory and antioxidative activities.”

The researchers hope the work may lead to an effective therapy for Parkinson’s Disease, an incurable, progressive neurogenerative disorder which affects more than 10 million people worldwide, including a million in the United States, according to the Mayo Clinic. Most patients are men aged 65 or over. 

“Basically, kurarinone targets the soluble epoxide hydrolase (sEH), which is a key regulatory enzyme involved in the metabolism of fatty acids, and inhibitors of the sEH enzyme resolve neuroinflammation,” said a corresponding author of the paper. “The enzyme regulates a newly studied class of natural chemical mediators, which in turn regulate inflammation, blood pressure and pain. 

“We have known for a number of years that the soluble epoxide hydrolase inhibitors, now in human safety trials, are active in reducing the development of Parkinson’s disease in several rodent models,” the senior author said.

Because of regulatory differences, a natural product offers a potentially faster route to relief for patients than a classical pharmaceutical, the author said. 

Kurarinone has a novel mechanism compared to other sEH inhibitors, binding the enzyme in an adjacent but non-identical site. This provides a new model for the design of still more active compounds to block neuroinflammation associated with diseases where sEH inhibitors have shown efficacy in rodent models including Alzheimer’s, autism and other disorders, the author said.  

The research used a model of Parkinson’s Disease in mice treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Parkinson-like behaviors were significantly alleviated in mice treated with kurarinone. When tested in gene-modified mice with their sEH gene knocked out, kurarinone did not provide additional protection.   

Sophora (the Arabic name for a pea-flowered tree) is a genus of about 45 species of evergreen trees and shrubs in the pea family, Fabaceae. The species are native to southern Asia, Australasia, various Pacific islands, western South America, the western United States, Florida and Puerto Rico. About fifteen of these species have a long history of use in traditional Chinese medicines. 

https://www.pnas.org/doi/10.1073/pnas.2118818119