Abstract
Aim:
To investigate the effect of ginsenoside Rg1, an effective ingredient from ginsenoside, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced substantia nigra neuron lesion.
Methods:
C57-BL mice were given MPTP to prepare Parkinson disease mice model. Different doses of Rg1 (5, 10, and 20 mg·kg−1·d−1) or N-acetylcystein (NAC) (300 mg·kg−1·d−1) were given 3 d prior to MPTP in the pretreatment groups. Glutathione (GSH) level and total superoxide dismutase (T-SOD) activity in substantia nigra were determined by spectrophotometry. Nissl staining, tyrosine hydroxylase immunostaining, and TUNEL labeling were used to observe the damage and apoptosis of nigral neurons. Western blot analysis was used to detect the phospho-JNK and phospho-c-Jun levels in midbrain homogenates.
Results:
Pretreatments of C57-BL mice with different doses of Rg1 or NAC were found to protect against MPTP-induced substantia nigra neurons loss. Rg1 or NAC prevented GSH reduction and T-SOD activation in substantia nigra, and attenuated the phosphorylations of JNK and c-Jun following MPTP treatment.
Conclusion:
The antioxidant property of Rg1 along with the blocking of JNK signaling cascade might contribute to the neuroprotective effect of ginsenoside Rg1 against MPTP.
Similar content being viewed by others
Article PDF
References
Gerlach M, Ben-Shachar D, Riederer P, Youdim MB . Altered brain metabolism of iron as a cause of neurodegenerative diseases? J Neurochem 1994; 63: 793–806.
Jenner P, Olanow CW . Pathological evidence for oxidative stress in Parkinson's disease and related degenerative disorders. In: Olanow CW, Jenner P, Youdim MBH, editors. Neurodegeneration and neuroprotection in Parkinson's disease. London: Academic Press; 1996. p 24–45.
Alam ZI, Jenner A, Daniel SE, Lees AJ, Cairns N, Marsden CD, et al. Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J Neurochem 1997; 69: 1195–203.
Dexter DT, Holley AE, Flitter WD, Slater TF, Wells FR, Daniel SE, et al. Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: an HPLC and ESR study. Mov Disord 1994; 9: 92–7.
Zhang J, Perry G, Smith MA, Robertson D, Olson SJ, Graham DG, et al. Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol 1999; 154: 1423–9.
Ramsay RR, Salach JI, Dadgar J, Singer TP . Inhibition of mitochondrial NADH dehydrogenase by pyridine derivatives and its possible relation to experimental and idiopathic parkinsonism. Biochem Biophys Res Commun 1986; 135: 269–75.
Saporito MS, Brown EM, Miller MS, Carswell S . CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl-tetrahydro-pyridine-mediated loss of nigrostriatal dopaminergic neurons in vivo. J Pharmacol Exp Ther 1999; 288: 421–7.
Xia XG, Harding T, Weller M, Bieneman A, Uney JB, Schulz JB . Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease. Proc Natl Acad Sci USA 2001; 98: 10433–8.
Maroney AC, Finn JP, Bozyczko-Coyne D, O'Kane TM, Neff NT, Tolkovsky AM, et al. CEP-1347 (KT-7515), an inhibitor of JNK activation, rescues sympathetic neurons and neuronally differentiated PC12 cells from death evoked by three distinct insults. J Neurochem 1999; 73: 1901–12.
Rudakewich M, Ba F, Benishin CG . Neurotrophic and neuroprotective actions of ginsenoside Rb(1) and Rg(1). Planta Med 2001; 67: 533–7.
Chen XC, Chen Y, Zhu YG, Fang F, Chen LM . Protective effect of ginsenoside Rg1 on MPTP-induced apoptosis in mouse substantia nigra neurons and its mechanisms. Acta Pharmacol Sin 2002; 23: 829–34.
Chen XC, Zhu YG, Zhu LA, Huang C, Chen Y, Chen LM, et al. Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress. Eur J Pharmacol 2003; 473: 1–7.
Perry TL, Yong VW, Clavier RM, Jones K, Wright JM, Foulks JG, et al. Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine by four different antioxidants in the mouse. Neurosci Lett 1985; 60: 109–14.
Saporito MS, Thomas BA, Scott RW . MPTP activates c-Jun NH2-terminal kinase (JNK) and its upstream regulatory kinase MKK4 in nigrostriatal neurons in vivo. J Neurochem 2000; 75: 1200–8.
Bradford MM . A rapid and sensitive for the quantitation of microgram quantitites of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–54.
Liao B, Newmark H, Zhou R . Neuroprotective effects of ginseng total saponins and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro. Exp Neurol 2002; 173: 224–34.
Ali SF, David SN, Newport GD, Cadet JL, Slikker W Jr . MPTPinduced oxidative stress and neurotoxicity are age-dependent: evidence from measures of reactive oxygen species and striatal dopamine levels. Synapse 1994; 18: 27–34.
Grunblatt E, Mandel S, Maor G, Youdim MBH . Effect of R- and S-apomorphine on MPTP-induced nigro-striatal dopamine neuronal loss. J Neurochem 2001; 77: 146–56.
Sriram K, Pai KS, Boyd MR, Ravindranath V . Evidence for generation of oxidative stress in brain by MPTP: in vitro and in vivo studies in mice. Brain Res 1997; 749: 44–52.
Marttila RJ, Lorentz H, Rinne UK . Oxygen toxicity protecting enzymes in Parkinson's disease. Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus. J Neurol Sci 1988; 86: 321–31.
Saggu H, Cooksey J, Dexter D, Wells FR, Lees A, Jenner P, et al. A selective increase in particulate superoxide dismutase activity in Parkinsonian substantia nigra. J Neurochem 1989; 53: 692–7.
Yoritaka A, Hattori N, Mori H, Kato K, Mizuno Y . An immunohistochemical study on manganese superoxide dismutase in Parkinson's disease. J Neurol Sci 1997; 148: 181–6.
Ziv I, Offen D, Barzilai A, Haviv R, Stein R, Zilkha-Falb R, et al. Modulation of control mechanism of dopamine-induced apoptosis-a future approach to the treatment of Parkinson's disease? J Neural Transm Suppl 1997; 49: 195.
Offen D, Ziv I, Panet H, Wasserman L, Stein R, Melamed E, et al. Dopamine-induced apoptosis is inhibited in PC12 cells expressing Bcl-2. Mol Cell Neurol 1997; 17: 289–304.
Hochman A, Sternin H, Gorodin S, Korsmeyer S, Ziv I, Melamed E, et al. Enhanced oxidative stress and altered antioxidants in brains of Bcl-2-deficient mice. J Neurochem 1998; 71: 741–8.
Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA . Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitrite oxide and superoxide. Proc Natl Acad Sci USA 1990; 87: 1620–4.
Lin KT, Xue JY, Nomen M, Spur B, Wong PY . Peroxynitrite-induced apoptosis in HL-60 cells. J Biol Chem 1995; 270: 16487–90.
Dehmer T, Lindenau J, Haid S, Dichgans J, Schulz JB . Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J Neurochem 2000; 74: 2213–6.
Hunot S, Boissiere F, Faucheux B, Brugg B, Mouatt-Prigent A, Agid Y, et al. Nitrite oxide synthase and neuronal vulnerability in Parkinson's disease. Neuroscience 1996; 72: 355–63.
Chen XC, Fang F, Zhu YG, Chen LM, Zhou YC, Chen Y . Protective effect of ginsenoside Rg1 on MPP+-induced apoptosis in SHSY5Y cells. J Neural Transm 2003; 110: 835–45.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by Major Funding from the Fujian Department of Education (JA02219) and Key Grant from the Fujian Science and Technology Bureau (2001Z037).
Rights and permissions
About this article
Cite this article
Chen, Xc., Zhou, Yc., Chen, Y. et al. Ginsenoside Rg1 reduces MPTP-induced substantia nigra neuron loss by suppressing oxidative stress. Acta Pharmacol Sin 26, 56–62 (2005). https://doi.org/10.1111/j.1745-7254.2005.00019.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2005.00019.x
Keywords
This article is cited by
-
Swimming training and herbal nanoformulations as natural remedies to improve sensory-motor impairment in rat midbrain tumor models: system biology, behavioral test, and experimental validation
3 Biotech (2023)
-
Ginsenoside Rg1 exerts neuroprotective effects in 3-nitropronpionic acid-induced mouse model of Huntington’s disease via suppressing MAPKs and NF-κB pathways in the striatum
Acta Pharmacologica Sinica (2021)
-
Rg1 improves LPS-induced Parkinsonian symptoms in mice via inhibition of NF-κB signaling and modulation of M1/M2 polarization
Acta Pharmacologica Sinica (2020)
-
Ginsenoside Rg1 protects against ischemic/reperfusion-induced neuronal injury through miR-144/Nrf2/ARE pathway
Acta Pharmacologica Sinica (2019)
-
Traditional Chinese medicine for modern treatment of Parkinson’s disease
Chinese Journal of Integrative Medicine (2017)