The component derived from turmeric essential oil exhibits neuroprotective effects

Researchers at Kumamoto University, Japan, have found that a component derived from turmeric essential oil, aromatic turmerone (ar-turmerone), and its derivatives act directly on dopaminergic nerves to create a neuroprotective effect on tissue cultures from a model of Parkinson’s disease. This appears to be due to increased cellular antioxidant power due to activation of Nrf2. The researchers believe that the ar-turmerone derivatives identified in this study may be used as new therapeutic agents for Parkinson’s disease.

Parkinson’s disease is a neurodegenerative disease caused by the selective death of dopaminergic neurons that carry information from the substantia nigra of the midbrain to the striatum, resulting in decreased production of dopamine. Symptoms include limb tremors, immobility, muscle stiffness, and other movement disorders. Treatments, such as dopamine supplements, are currently available, but there is still no way to inhibit dopaminergic neurodegeneration.

Previous studies have reported that the inflammatory response caused by the activation of microglia (cells responsible for immune function in the brain) is observed in the substantia nigra of the midbrain of patients with Parkinson’s disease. Further experiments designed to mimic the in vivo state of the midbrain (culture of midbrain slices) revealed that microglial activation triggers selective degeneration of dopaminergic neurons in substantia nigra, and that the derivative nitric oxide (NO) activated microglia is involved in neurodegeneration. These results suggest that compounds with anti-inflammatory effects on microglia may suppress dopaminergic degeneration.

Thus, the researchers analyzed aromatic tumerone (ar-turmerone), a major component of turmeric essential oil that is believed to have anti-tumor and anti-inflammatory effects on microglia. They used the BV2 microglial cell line and midbrain slice cultures to 1) determine whether ar-turmerone suppresses dopaminergic neurodegeneration through its anti-inflammatory effects, and 2) identify structurally similar compounds (derivatives) that could have stronger anti-inflammatory and neuroprotective effects.

Ar-turmerone has an asymmetric carbon (S-Tur). The researchers therefore prepared eight analogues and attempted to identify those with more potent anti-inflammatory effects. They used the inhibitory effects on the inflammatory response induced by lipopolysaccharide (LPS) stimulated activation of BV2 cells as an indicator. Analogs with stronger anti-inflammatory effects than S-Tur were (R) -ar-turmerone (R-Tur), ar-atlantone (Atl) and analog 2 (A2).

To examine whether these compounds, including S-Tur, have an inhibitory effect on dopaminergic degeneration, the researchers next observed cultures of midbrain slices in which microglial activation was induced by interferon-γ and stimulation of the brain. LPS (IFN-γ / LPS). All four compounds significantly suppressed a decrease in the number of dopaminergic neurons induced by IFN-γ / LPS. However, the production of NO, which is released from activated microglia and is involved in dopaminergic neurodegeneration, was not inhibited at all. In addition, three compounds, S-Tur, Atl and A2, inhibited dopaminergic degeneration induced by MPP +, a toxin that selectively damages dopaminergic neurons independent of microglial activity. These results indicate that S-Tur and its derivatives, Atl and A2, have a direct effect on dopaminergic neurons and exhibit neuroprotective effects. In addition, analysis using dopaminergic progenitor cell lines and midbrain slice cultures revealed that the neuroprotective effects of Atl and A2 are mediated by activation of Nrf2, a transcription factor that enhances the antioxidant power of cells. .

Our study elucidated a novel mechanism by which ar-turmerone and its derivatives directly protect mesencephalic dopaminergic neurons, independent of their previously reported anti-inflammatory effects on microglia. We have shown that two derivatives, Atl and A2, exhibit neuroprotective effects by increasing the expression of antioxidant proteins thanks to the activation of Nrf2. In particular, the A2 analogue identified in this study is a potent activator of Nrf2 and is believed to have a strong antioxidant effect. We believe that it is possible that this compound may be a novel dopaminergic neuroprotective agent for the treatment of Parkinson’s disease, and that it may also be used to treat other diseases caused by oxidative stress, such as heart disease. liver and kidneys. “

Takahiro Seki, Associate Professor, Kumamoto University

This research was posted in Cells on May 3, 2021.