6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation

Aim: 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown various neurobiological and anti-inflammatory effects. The aim of this study was to examine the effects of 6-shogaol on neuroinflammatory-induced damage of dopaminergic (DA) neurons in Parkinson's disease (PD) models. Methods: Cultured rat mesencephalic cells were treated with 6-shogaol (0.001 and 0.01 mu mol/L) for 1 h, then with MPP+ (10 mu mol/L) for another 23 h. The levels of TNF-alpha and NO in medium were analyzed spectrophotometrically. C57/BL mice were administered 6-shogaol (10 mg.kg(-1).d(-1), po) for 3 d, and then MPTP (30 mg/kg, ip) for 5 d. Seven days after the last MPTP injection, behavioral testings were performed. The levels of tyrosine hydroxylase (TH) and macrophage antigen (MAC)-1 were determined with immunohistochemistry. The expression of iNOS and COX-2 was measured using RT PCR. Results: In MPP+-treated rat mesencephalic cultures, 6-shogaol significantly increased the number of TH-IR neurons and suppressed TNF-alpha and NO levels. In C57/BL mice, treatment with 6-shogaol reversed MPTP-induced changes in motor coordination and bradykinesia. Furthermore, 6-shogaol reversed MPTP-induced reductions in TH-positive cell number in the substantia nigra pars compacta (SNpc) and TH-IR fiber intensity in stratum (ST). Moreover, 6-shogaol significantly inhibited the MPTP-induced microglial activation and increases in the levels of TNF-alpha, NO, iNOS, and COX-2 in both SNpc and ST. Conclusion: 6-Shogaol exerts neuroprotective effects on DA neurons in in vitro and in vivo PD models.