Inhibitory effect of thiacremonone on MPTP-induced dopaminergic neurodegeneration through inhibition of p38 activation

Abstract

Neuroinflammation is implicated for dopaminergic neurodegeneration. Sulfur compounds extracted from garlic have been shown to have anti-inflammatory properties. Previously, we have investigated that thiacremonone, a sulfur compound isolated from garlic has anti-inflammatory effects on several inflammatory disease models. To investigate the protective effect of thiacremonone against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral impairment and dopaminergic neurodegeneration, 8 week old ICR mice were given thiacremonone (10 mg/kg) in drinking water for 1 month and received intraperitoneal injection of MPTP (15 mg/kg, four times with 2 h interval) during the last 7 days of treatment. Our data showed that thiacremonone decreased MPTP-induced behavioral impairments (Rotarod test, Pole test, and Gait test), dopamine depletion and microglia and astrocytes activations as well as neuroinflammation. Higher activation of p38 was found in the substantia nigra and striatum after MPTP injection, but p38 activation was reduced in thiacremonone treated group. In an in vitro study, thiacremonone (1, 2, and 5 μg/ml) effectively decreased MPP+ (0.5 mM)-induced glial activation, inflammatory mediators generation and dopaminergic neurodegeneration in cultured astrocytes and microglial BV-2 cells. Moreover, treatment of p38 MAPK inhibitor SB203580 (10 μM) further inhibited thiacremonone induced reduction of neurodegeneration and neuroinflammation. These results indicated that the anti-inflammatory compound, thiacremonone, inhibited neuroinflammation and dopaminergic neurodegeneration through inhibition of p38 activation.

Neuroprotective Potential of Allium sativum against Monosodium Glutamate-Induced Excitotoxicity: Impact on Short-Term Memory, Gliosis, and Oxidative Stress

“…This neuroprotective activity of Allium sativum is attributed to the ability of garlic-derived organosulfur compounds-DAD and DAT-to modulate redox activity and to reduce oxidative stress and their incorporation in many signaling pathways [47]. Diallyl disulfide was proven as a strong lipid peroxidation terminator [55], thus providing neuronal protection and preventing neuronal damage by excitotoxins. The protective effect of Allium sativum against MSG-induced hippocambal neurons agreed with the finding of Hwang et al [55], who reported that garlic protected dopaminergic neurons from degeneration in a Parkinson rat model.…”

“…Diallyl disulfide was proven as a strong lipid peroxidation terminator [55], thus providing neuronal protection and preventing neuronal damage by excitotoxins. The protective effect of Allium sativum against MSG-induced hippocambal neurons agreed with the finding of Hwang et al [55], who reported that garlic protected dopaminergic neurons from degeneration in a Parkinson rat model. The authors also found that it decreased astrocyte activation and neural inflammation.…”

Protective effects of DL-3-n-butylphthalide in the lipopolysaccharide-induced mouse model of Parkinson's disease

“…The inhibitor of JNK, SR-3306, can reduce the loss of neurons in a rat model of PD, suggesting that JNK inhibitors possess a protective effect on neurons in PD (35). p38 is also activated in neurotoxic PD models (36). Furthermore, inhibitors of p38 are effective in the treatment of PD (4).…”

Neuroprotective effects of antioxidants in the management of neurodegenerative disorders: A literature review

“…47 There are convincing, evidence-based literature references, which have demonstrated that garlic extract and its major ingredients have potent antioxidant activity. 47,48 Hwang et al 49 recently reported that thiacremonone, which is isolated from garlic, inhibits p38 activation and protects against substantia nigra impairment. Brunetti et al 50 have shown that garlic supplementation can be effective against oxidative damage to the brain, although this effect was not seen in the older animals tested.…”

“…Abe and Saito, 36 Bandegi et al, 38 Hosseinzadeh et al, 39 Soeda et al, 40 Khalili and Hamzeh, 41 Naghizadeh et al 42 Olive oil Moreno et al, 44 Moreno, 45 and Rodríguez-Morató et al 46 Garlic extract Hwang et al, 49 Brunetti et al, 50 and Mbyirukira and Gwebu 51…”