Table 1. Preclinical Evidence on the Potential Mechanisms of Action of Ginger in Parkinson’s Disease^a.

constituent	study type	subjects	route of administration and dose	main effects and potential mechanism of action	references
zingerone	in vivo	6-OHDA-treated mice	intraperitoneally, 65 nmol/kg body weight	improvement of endogenous antioxidant mechanisms (enhanced systematic SOD activity)	(35)
zingerone and levodopa (cotreatment)	in vivo	6-OHDA-treated mice	orally, 0.7 μmol/kg/day	reduced ability of recovery of dopaminergic neurons after 6-OHDA-injection; reduced catalase activity and oxidized l-ascorbate	(36)
6-shogaol	in vitro	LPS-treated primary microglial cells	10 μM	reduced LPS-induced NO production and iNOS expression	(37)
6-gingerol	in vitro	6-OHDA-treated PC12 cells	2.5 and 5 μM	inhibited 6-OHDA-induced cell apoptosis (2.5 and 5 μM), accompanied by lower levels of the activated form of SAPK/JNK (2.5 μM)	(38)
6-shogaol	in vitro	MPP+-treated primary rat mesencephalic cultures	0.001 and 0.01 μmol/L	increased survival of dopaminergic neurons and lower NO and TNF-α levels	(43)
6-shogaol	in vivo	MPTP-treated C57/BL mice	Orally, 10 mg/kg/day	improved bradykinesia and motor coordination; prevented dopaminergic loss in SNpc and nigrostriatal innervation; suppressed microglia activation; reduced levels of NO, iNOS, TNF-α, and COX-2 in the SNpc and striatum	(43)
6-gingerol	in vitro	LPS-treated C6 astroglioma cells	5 and 20 μM	inhibited LPS-induced neuroinflammation, reduced TNF-α,IL-6, ROS, NO and iNOS levels	(44)
6-gingerol	in vivo	LPS-treated rats	intraperitoneally, 0.5 or 2 mg/kg	inhibited LPS-induced cognitive impairment, and TNF-α (2 mg/kg) and GFAP (0.5 and 2 mg/kg) increase	(44)
zingerone	in vivo	MPTP-treated C57BL/6 mice	intraperitoneally, 10 mg/kg/day	increased neuronal cell viability	(46)
zingerone	in vitro	MPP+-treated dopaminergic neuronal cells	2 mM	increased neuronal cell viability; increased ERK activation and VMAT2 expression	(46)
ginger and 6-shogaol	in vivo	MPTP-treated C57BL/6J mice	ginger (30, 100, 300 mg/kg) and 6-shogaol(10 mg/kg)	prevented the intestinal integrity impairment and dopaminergic neuronal loss in the enteric nervous system; increased ZO-1 and occludin levels in the colon; downregulation of iNOS, TNF-α,IL-1β, and COX-2 and phosphorylation of ERK1/2; restored Bax to Bcl-2 ratio, cytochrome C, cleaved caspase-3, and HO-1 levels	(14)

^a6-OHDA, 6-hydroxydopamine; SOD, superoxide dismutase; LPS, lipopolysaccharide; iNOS, inducible nitric oxide synthase; VMAT2, vesicular monoamine transporter 2; GFAP, glial fibrillary acidic protein; ERK1/2, extracellular signal-regulated kinase 1/2.