Ingredients derived from turmeric essential oils have a neuroprotective effect

Researchers at Kumamoto University in Japan have found that aromatic turmerone, a component derived from turmeric essential oils, and its derivatives act directly on dopaminergic nerves to provide a neuroprotective effect on tissue culture of Parkinson’s disease models. I found it to bring. This is thought to be due to the enhancement of the antioxidant power of the cells by the activation of Nrf2. Researchers believe that the altermeron derivatives identified in this study could be used as a new treatment for Parkinson’s disease.

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

Previous studies have reported that an inflammatory response caused by activation of microglia (cells involved in the immune function of 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 (midbrain slice culture) show that activation of microglia causes selective degeneration of substantia nigra dopaminergic neurons and monoxide derived from activated microglia. It was revealed that nitrogen (NO) is involved in neurodegeneration. These findings suggest that compounds with anti-inflammatory effects on microglia may suppress dopaminergic degeneration.

Therefore, researchers analyzed the aromatic turmerone, the main component of turmeric essential oils, which have been reported to have antitumor and anti-inflammatory effects on microglia. They used BV2 microglial cell lines and midbrain slice cultures to determine 1) whether Altermeron suppresses dopaminergic neurodegeneration through its anti-inflammatory effects, and 2) stronger anti-inflammatory and neurological. We have identified structurally similar compounds (derivatives) that may have protective effects.

Since Ar-turmerone has an asymmetric carbon (S-Tur), researchers have prepared eight analogs to try to identify those with stronger anti-inflammatory effects. They used the inhibitory effect on the inflammatory response evoked by the activation of BV2 cells stimulated by lipopolysaccharide (LPS) 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 determine if these compounds, including S-Tur, have an inhibitory effect on dopaminergic degeneration, researchers then investigated that microglial activation was interferon-γ and LPS-stimulated (IFN-γ / LPS). ) Induced midbrain slice culture was observed. All four compounds significantly suppressed the decrease in the number of dopaminergic neurons induced by IFN-γ / LPS. However, the production of NO released from activated microglia and involved in dopaminergic neurodegeneration was not inhibited at all. In addition, three compounds, S-Tur, Atl, and A2, suppressed dopaminergic degeneration induced by MPP +, a toxin that selectively damages dopaminergic neurons independently of microglial activity. .. These results indicate that S-Tur and its derivatives Atl and A2 have a direct effect on dopaminergic neurons and have a neuroprotective effect. Furthermore, analysis using dopaminergic progenitor cell lines and midbrain slice cultures reveals that the neuroprotective effects of Atl and A2 are mediated by activation of Nrf2, a transcription factor that enhances cell antioxidant capacity. became.

Our study elucidated a new mechanism by which altermeron and its derivatives directly protect midbrain sliced ​​dopaminergic neurons, independent of previously reported anti-inflammatory effects on microglia. Two derivatives, Atl and A2, have been shown to exhibit neuroprotective effects by increasing antioxidant protein expression through activation of Nrf2. In particular, the analog A2 identified in this study is a potent activator of Nrf2 and is thought to have potent antioxidant activity. The compound may be a new dopaminergic neuroprotective agent for the treatment of Parkinson’s disease, and we believe it can also be used to treat other diseases caused by oxidative stress, such as liver and kidney diseases. “

Takahiro Seki, Associate professor, Kumamoto University

This survey was posted online cell May 3, 2021.