Herbal compound boosts levodopa effectiveness in Parkinson’s rats

A compound derived from a Himalayan herb may help boost the effectiveness of levodopa in Parkinson’s disease, according to a study done in rats.

Data indicate that co-administration of the herbal compound with levodopa leads to higher dopamine levels in the brain due to changes in the activity of gut bacteria.

The researchers stressed that more studies are needed to fully understand these mechanisms and their potential relevance for patients.

The study, “Modulation of gut microbiota by nardosinone augments the efficacy of levodopa in rotenone-induced Parkinson’s disease rats,” was published in npj Biofilms and Microbiomes.

Parkinson’s is caused when brain cells that make dopamine, a key signaling molecule, are lost. Low dopamine levels disrupt nerve signaling, ultimately driving Parkinson’s symptoms.

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Levodopa is a mainstay treatment for Parkinson’s. It works by providing brain cells with more raw material to manufacture dopamine, thereby boosting dopamine levels and normalizing neural signaling to ease Parkinson’s symptoms.

Nardosinone is a compound derived from Indian spikenard, an herb that grows in the Himalayas. Lab studies suggest that nardosinone may have neuroprotective properties, but its effects in Parkinson’s are largely unknown. 

Researchers in China tested the effects of co-administering levodopa and nardosinone to rats, and found that it resulted in higher levodopa levels in the blood and higher dopamine levels in the brain.

Further tests showed that nardosinone’s levodopa-boosting effects were blunted when rats were given an antibiotic (a medication that kills bacteria). This implies that nardosinone may boost levodopa’s activity by modulating the activity of the bacteria that inhabit the digestive tract, collectively known as the gut microbiome.

Building on this hypothesis, the researchers conducted fecal transplant experiments in which gut bacteria from rats treated with nardosinone and levodopa were transplanted into the intestines of a Parkinson’s rat model pretreated with antibiotics. The researchers found that gut bacteria from rats given both nardosinone and levodopa led to improvements in motor function tests and better survival of dopamine-making nerve cells in the recipient rats. These data support the idea that nardosinone’s effect on levodopa is modulated, at least in part, by gut bacteria.

Data also indicated that nardosinone and levodopa led to reduced inflammation and better integrity of the intestinal barrier in the gut, while in the brain, the combination treatment was associated with increased levels of certain enzymes that are needed to make dopamine. These changes may also contribute to the effects of co-treatment, the researchers said.

“This exploratory study demonstrated an association among nardosinone [plus levodopa] coadministration, gut microbiota compositional shifts, and improved motor and [tissue-based] outcomes in a [Parkinson’s] rat model,” the researchers concluded.

The scientists stressed that, from the available data, it’s not possible to draw any definitive conclusions about cause and effect, and they called for further studies to investigate these mechanisms further. Still, they said the overall findings suggest that nardosinone may increase levodopa’s activity in Parkinson’s.