Oxidative injury has been implicated in the aetiology of Parkinson's disease (PD) and gypenosides (GP), which are saponins with various bioactivities, have shown antioxidative effects in vitro. The present study was designed to evaluate the effect of GP on a 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-induced mouse model of PD. Acute administration of MPTP led to decreased glutathione content and reduced superoxide dismutase activity in the substantia nigra of the mice, which resulted in oxidative
stress, loss of nigral dopaminergic neurons and motor dysfunction. Co-treatment with GP attenuated all the injuries induced by MPTP in a dose-dependent manner. The neuroprotective effect of GP may be attributed to increased antioxidation, as manifested by significantly increased glutathione content and enhanced superoxide dismutase activity in the substantia nigra. These results strongly indicate the possible therapeutic potential of GP as an antioxidant in PD.
DauerWPrzedborskiS: Parkinson's disease: Mechanisms and models. Neuron2003; 39: 889–909.
2.
FahnSCohenG: The oxidant stress hypothesis in Parkinson's disease: Evidence supporting it. Ann Neurol1992; 32: 804–812.
3.
AdamsJDJrChangMLKlaidmanL: Parkinson's disease: Redox mechanisms. Curr Med Chem2001; 8: 809–814.
4.
SoficELangeKWJellingerK: Reduced and oxidised glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci Lett1992; 142: 128–130.
5.
SianJDexterDTLeesAJ: Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol1994; 36: 348–355.
6.
SaravananKSSindhuKMMohanakumarKP: Melatonin protects against rotenone-induced oxidative stress in a hemiparkinsonian rat model. J Pineal Res2007; 42: 247–253.
7.
VermaRNehruB: Effect of centrophenoxine against rotenone-induced oxidative stress in an animal model of Parkinson's disease. Neurochem Int2009; 55: 369–375.
8.
DexterDTHolleyAEFlitterWD: Increased levels of hydroperoxides in the parkinsonian substantia nigra–an HPLC and ESR study. Mov Disord1994; 9: 92–97.
9.
YoritakaAHattoriNUchidaK: Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA1996; 93: 2696–2701.
10.
AlamZIDanielSELeesAJ: A generalized increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease. J Neurochem1997; 69: 1326–1329.
11.
AlamZIJennerADanielSE: Oxidative DNA damage in the parkinsonian brain: An apparent selective increase in 8-hydroxyguanine in substantia nigra. J Neurochem1997; 69: 1196–1203.
12.
ChenJCTsaiCCChenLD: Therapeutic effect of gypenoside on chronic liver injury and fibrosis induced by CCl4 in rats. Am J Chin Med2000; 28: 175–185.
13.
La CourBMolgaardPYiZ: Traditional Chinese medicine in treatment of hyperlipidaemia. J Ethnopharmacol1995; 46: 125–129.
14.
MegalliSAktanFDaviesNM: Phytopreventative anti-hyperlipidemic effects of Gynostemma pentaphyllum in rats. J Pharm Pharm Sci2005; 8: 507–515.
15.
WangQFChenJCHsiehSJ: Regulation of Bcl-2 family molecules and activation of caspase cascade involved in gypenosides induced apoptosis in human hepatoma cells. Cancer Lett2002; 183: 169–178.
16.
ShangLLiuJZhuQ: Gypenosides protect primary cultures of rat cortical cells against oxidative neurotoxicity. Brain Res2006; 1102: 163–174.
17.
OgawaNHiroseYOharaS: A simple quantitative bradykinesia test in MPTP-treated mice. Res Commun Chem Pathol Pharmacol1985; 50: 435–441.
18.
RozasGGarciaJL Labandeira: Drug-free evaluation of rat models of parkinsonism and nigral grafts using a new automated rotarod test. Brain Res1997; 749: 188–199.
19.
NovikovaLGarrisBLGarrisDR: Early signs of neuronal apoptosis in the substantia nigra pars compacta of the progressive neurodegenerative mouse 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine probenecid model of Parkinson's disease. Neuroscience2006; 140: 67–76.
20.
CassWAHarnedMEPetersLE: HIV-1 protein Tat potentiation of methamphetamine-induced decreases in evoked overflow of dopamine in the striatum of the rat. Brain Res2003; 984: 133–142.
21.
SmithMPCassWA: Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson's disease. Neuroscience2007; 144: 1057–1066.
22.
TietzeF: Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Anal Biochem1969; 27: 502–522.
23.
KonoY: Generation of superoxide radical during auto-oxidation of hydroxylamine and an assay of superoxide dismutase. Arch Biochem Biophys1978; 186: 189–195.
24.
PoonHFJoshiGSultanaR: Antisense directed at the Aβ region of APP decreases brain oxidative markers in aged senescence accelerated mice. Brain Res2004; 1018: 86–96.
25.
WillsED: Mechanism of lipid peroxide formation in animal tissue. Biochem J1966; 99: 667–676.
