Abstract
In Parkinson’s disease clinical and experimental evidence suggest that neuroinflammatory changes in cytokines caused by microglial activation contribute to neuronal death. Experimentally, neuroinflammation of dopaminergic neurons can be evoked by lipopolysaccharide (LPS) exposure. In mesencephalic primary cultures LPS (100μg/ml) resulted in 30–50% loss of dendritic processes, changes in the perikarya, cellular atrophy and neuronal cell loss of TH-immunoreactive (TH+) cells. iNOS activity was increased dose dependently as well as prostaglandin E2 concentrations. Ginsenosides, as the active compounds responsible for ginseng action, are reported to have antioxidant and anti-inflammatory effects. Here ginsenoside Rd was used to counteract LPS neurodegeneration. Partial reduction of LPS neurotoxic action was seen in dopaminergic neurons. Cell death by LPS as well as neuroprotective action by ginsenoside Rd was not selective for dopaminergic neurons. Neuronal losses as well as cytoprotective effects were similar when counting NeuN identified neurons. The anti-inflammatory effect of ginsenoside Rd could equally be demonstrated by a reduction of NO-formation and PGE2 synthesis. Thus, protective mechanisms of ginsenoside Rd may involve interference with iNOS and COX-2 expression.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
References
Bae EA, Kim EJ, Park JS (2006) Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-gamma-stimulated BV-2 microglial cells. Planta Med 72(7): 627–633
Bal-Price A, Matthias A, Brown GC (2002) Stimulation of the NADPH oxidase in activated rat microglia removes nitric oxide but induces peroxynitrite production. J Neurochem 80: 73–80
Beckman JS, Crow JP (1993) Pathological implications of nitric oxide, Superoxide and peroxynitrite formation. Biochem Soc Trans 21: 330–334
Cho JY, Park J, Yoo ES, Baik KU, Park MH (1998) Effect of ginseng saponin in tumor necrosis factor-α production and T cell proliferation. Yakhak Hoegi 43: 296–301
Chock VY, Giffard RG (2005) Development of neonatal murine microglia in vitro: changes in response to lipopolysaccharide and ischemia-like injury. Pediatr Res 57: 475–480
Choi SS, Lee JK, Han EJ, Han KJ, Lee HK (2003) Effect of ginsenoside Rd on nitric oxide system induced by lipopolysaccharide plus TNF-alpha in C6 rat glioma cells. Arch Pharm Res 26: 375–382
Gayle DA, Ling ZD, Tong CW, Landers T, Lipton JW (2001) Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factors-α, interleukin-1ß, and nitric oxide. Dev Brain Res 133: 27–35
Heneka MT, Feinstein DL, Galea E (1999) Peroxisome proliferator-activated receptor gamma agonists protect cerebellar granule cells from cytokine-induced apoptotic cell death by inhibition of inducible nitric oxide synthase. J Neuroimmunol 100: 156–168
Hunot S, Hirsch EC (2003) Neuroinflammatory processes in Parkinson’s disease. Ann Neurol 53: S49–S60
Jeong CS, Hyun JE, Kim YS (2003) Ginsenoside Rbl: the anti-ulcer constituent from the head of Panax ginseng. Arch Pharm Res 26: 906–911
Jiang KY, Qian ZN (1995) Effect of Panax notoginseng saponins on posthypoxic cell damage of neurons in vitro. Zhongguo Yaoli Xuebao 16: 399–402
Keum YS, Han SS, Chun KS, Park KK (2003) Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutat Res 523–524: 75–85
Kim S, Rhim H (2004) Ginsenosides inhibit NMDA receptor-mediated epileptic discharge in cultured hippocampal neurons. Arch Pharm Res 27: 524–530
Kyrkanides S, Moore AH, Olschowka JA, Daeschner JC, Williams JP (2002) Cyclooxygenase-2 modulates brain inflammation-related gene expression in CNS radiation injury. Mol Brain Res 104: 159–169
Langford RM (2006) Pain management today — what have we learned? Clin Rheumatol 25: 2–8
Lee JK, Choi SS, Lee HK, Han KJ, Han EJ, Suh HW (2003) Effects of ginsenoside Rd and decursinol on the neurotoxic responses induced by kainic acid in mice. Planta Med 69: 230–234
Li FQ, Wang T, Pei Z, Liu B, Hong JS (2005) Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammationmediated degeneration of dopaminergic neurons. J Neural Transm 112: 331–347
Li JQ, Zhang JT (1997) Effect of age and ginsenoside Rgl on membrance fluidity of cortical cells in rats. Yao Xue Xue Bao 32: 23–27
Liu B, Hong JS (2003) Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. Trends Pharmacol Sci 24(8): 395–401
Min JK, Kim JH, Cho YL, Kwon YG (2006) (20S) Rg3 prevents endothelial cells apoptosis via inhibition of the mitochondrial apoptotic caspase pathway. Biochem Biophys Res Commun 349: 987–994
Minghetti L, Ajmone-Cat MA, De Berardinis MA, De Simone R (2005) Microglial activation in chronic neurodegenerative diseases: roles of apoptotic neurons and chronic stimulation. Brain Res Rev 48: 251–256
Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116: 201–211
Narumiya S, Sugimoto Y, Ushikubi F (1999) Prostanoid receptors: structures, properties, and functions. Physiol Rev 79: 1193–1226
Nishiyama N, Cho SI, Kitagama I, Saito H (1994) Malonylginsenoside Rbl potentiates nerve growth factor (NGF)-induced neurite outgrowth of cultured chick embryonic dorsal root ganglia. Biol Pharm Bull 17: 509–513
Park EK, Shin YW, Lee HU, Kim SS, Lee YC (2005) Inhibitory effect of ginsenoside Rbl and compound K on NO and prostaglandin E2 biosyntheses of RAW 264.7 cells induced by lipopolysaccaride. Biol Pharm Bull 28: 652–656
Radad K, Gille G, Moldzio R, Saito H, Rausch WD (2004) Ginsenosides Rbl and Rgl effects on mesencephalic dopaminergic cells stressed with glutamate. Brain Res 1021: 41–53
Radad K, Rausch WD, Gille G (2006) Rotenone induces cell death in primary dopaminergic culture by increase ROS production and inhibiting mitochondrial respiration. Neurochem Int 49: 379–386
Ruano D, Revilla E, Gavilan MP, Vizuete ML (2006) Role of p38 and inducible nitric oxide synthase in the in vivo dopaminergic cells’ degeneration induced by inflammatory processes after lipopolysaccharide injection. Neuroscience 104: 1157–1168
Smolinski AT, Pestka JJ (2003) Modulation of lipopolysaccharide-induced proinflammatory cytokine production in vitro and in vivo by the herbal constituents apigenin (chamomile), ginsenoside Rbl and parthenolide (feverfew). Food Chem Toxicol 41: 1381–1390
Takadera T, Ohyashiki T (2006) Prostaglandin E2 deteriorates N-methyl-D-aspartate receptor-mediated cytotoxicity possibly by activating EP2 receptors in cultured cortical neurons. Life Sci 78: 1878–1883
Wang T, Liu B, Zhang W (2004) Andrographolide reduces inflammationmediated dopaminergic neurodegeneration in mesencephalic neuronglia cultures by inhibiting microglial activation. J Pharmacol Exp Ther 308: 975–983
Yin MJ, Yamamoto Y, Gaynor RB (1998) The anti-inflammatory agents aspirin and salicylate inhibit the activity of κB kinase-β. Nature 396: 77–80
Yokozawa T, Satoh A, Cho EJ (2004) Ginsenoside-Rd attenuates oxidative damage related to aging in senescence-accelerated mice. J Pharm Pharmacol 56: 107–113
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer-Verlag
About this paper
Cite this paper
Lin, WM., Zhang, YM., Moldzio, R., Rausch, WD. (2007). Ginsenoside Rd attenuates neuroinflammation of dopaminergic cells in culture. In: Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (eds) Neuropsychiatric Disorders An Integrative Approach. Journal of Neural Transmission. Supplementa, vol 72. Springer, Vienna. https://doi.org/10.1007/978-3-211-73574-9_13
Download citation
DOI: https://doi.org/10.1007/978-3-211-73574-9_13
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-73573-2
Online ISBN: 978-3-211-73574-9
eBook Packages: MedicineMedicine (R0)