Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. The inflammatory activation of microglia participates in dopaminergic neurodegeneration in PD. Therefore, chemicals that inhibit microglial activation are considered to have therapeutic potential for PD. Aromatic (ar)-turmerone is a main component of turmeric oil extracted from Curcuma longa and has anti-inflammatory activity in cultured microglia. The aims of the present study are (1) to investigate whether naturally occurring S-enantiomer of ar-turmerone (S-Tur) protects dopaminergic neurons in midbrain slice cultures and (2) to examine ar-turmerone analogs that have higher activities than S-Tur in inhibiting microglial activation and protecting dopaminergic neurons. R-enantiomer (R-Tur) and two analogs showed slightly higher anti-inflammatory effects in microglial BV2 cells. S- and R-Tur and these two analogs reversed dopaminergic neurodegeneration triggered by microglial activation in midbrain slice cultures. Unexpectedly, this neuroprotection was independent of the inhibition of microglial activation. Additionally, two analogs more potently inhibited dopaminergic neurodegeneration triggered by a neurotoxin, 1-methyl-4-phenylpyridinium, than S-Tur. Taken together, we identified two ar-turmerone analogs that directly and potently protected dopaminergic neurons. An investigation using dopaminergic neuronal precursor cells suggested the possible involvement of nuclear factor erythroid 2-related factor 2 in this neuroprotection.

D-Cysteine Activates Chaperone-Mediated Autophagy in Cerebellar Purkinje Cells via the Generation of Hydrogen Sulfide and Nrf2 Activation

“…Since release of hydrogen sulfide immediately follows the treatment with Na 2 S, it can rapidly modify the cysteine residues of Keap1, leading to the dissociation of Nrf2 from Keap1 and subsequent Nrf2 elevation and activation [ 24 ]. This result is consistent with our previous finding that chemicals that directly interact with Keap1 immediately increase the amount of Nrf2 [ 48 ]. Activation of Nrf2 leads to upregulation of various antioxidative proteins, including NQO1 and heme oxygenase-1 (HO-1) [ 25 ].…”

Rapid Determination and Quality Control of Pharmacological Volatiles of Turmeric (Curcuma longa L.) by Fast Gas Chromatography–Surface Acoustic Wave Sensor

“…The sesquiterpenes such as caryophyllene, trans-α-bergamotene, curcumene, β-sesquiphellandrene, and curcumol have anti-inflammatory effects. The main component ar-turmerone has anti-inflammatory, anti-malarial, anti-cancer, and neuroprotective effects [ 21 , 22 , 23 ]. The literature has shown that ar-turmerone can protect the dopaminergic neurons in the midbrain, as evidenced by slice cultures of their activities [ 22 ].…”

“…The main component ar-turmerone has anti-inflammatory, anti-malarial, anti-cancer, and neuroprotective effects [ 21 , 22 , 23 ]. The literature has shown that ar-turmerone can protect the dopaminergic neurons in the midbrain, as evidenced by slice cultures of their activities [ 22 ]. Ar-turmerone has inhibitory effects against plasmodium falciparum 3D7 [ 23 ].…”

“…The sesquiterpenes such as caryophyllene, trans-α-bergamotene, curcumene, β-sesquiphellandrene, and curcumol have anti-inflammatory effects. The main component ar-turmerone has anti-inflammatory, anti-malarial, anti-cancer, and neuroprotective effects [21][22][23]. The According to the MS data, the compounds of seven characteristic peaks detected by GC-SAW were identified.…”

Impacts of Commonly Used Edible Plants on the Modulation of Platelet Function

“…Another compound isolated from C. Longa that possesses antiplatelet effects is the sesquiterpene ketone, aromatic-turmerone or ar-turmerone ( Figure 14 ), which is the major component of the essential oil (61.79%) and has antioxidant, anti-inflammatory, and anticancer effects [ 133 ]. In animal models, it demonstrated positive impacts on neurogenerative diseases, including Parkinson’s and epilepsy by exhibiting anticonvulsant and protective effects on neurons [ 134 , 135 , 136 ]. Antiplatelet effects of ar-turmerone were tested in rabbit isolated platelets induced by 2 µg/mL collagen at concentrations of 1, 5 and 10 µg/mL.…”