Neurite Outgrowth and Neuroprotective Effects of Quercetin from Caesalpinia mimosoides Lamk. on Cultured P19-Derived Neurons

Quercetin has been isolated for the first time from ethyl acetate extract of Caesalpinia mimosoides Lamk. C. mimosoides Lamk. (Fabaceae) or Cha rueat (Thai name) is an indigenous plant found in mixed deciduous forest in northern and north-eastern parts of Thailand. Thai rural people consume its young shoots and leaves as a fresh vegetable, as well as it is used for medicinal purposes.The antioxidant capacity in terms of radical scavenging activity of quercetin was determined as IC50 of 3.18 ± 0.07 µg/mL, which was higher than that of Trolox and ascorbic acid (12.54 ± 0.89 and 10.52 ± 0.48 µg/mL, resp.). The suppressive effect of quercetin on both purified and cellular acetylcholinesterase (AChE) enzymes was investigated as IC50 56.84 ± 2.64 and 36.60 ± 2.78 µg/mL, respectively. In order to further investigate the protective ability of quercetin on neuronal cells, P19-derived neurons were used as a neuronal model in this study. As a result, quercetin at a very low dose of 1 nM enhanced survival and induced neurite outgrowth of P19-derived neurons. Furthermore, this flavonoid also possessed significant protection against oxidative stress induced by serum deprivation. Altogether, these findings suggest that quercetin is a multifunctional compound and promising valuable drugs candidate for the treatment of neurodegenerative disease.

[1]  Xingshu Li,et al.  O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-β aggregation. , 2012, Bioorganic & medicinal chemistry.

[2]  S. Koppula,et al.  The Role of Bioactive Compounds on the Promotion of Neurite Outgrowth , 2012, Molecules.

[3]  L. Levin,et al.  Ordering of neuronal apoptosis signaling: a superoxide burst precedes mitochondrial cytochrome c release in a growth factor deprivation model , 2012, Apoptosis.

[4]  H. Lee,et al.  Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer's disease , 2012, Brain Research Bulletin.

[5]  Irene Bolea,et al.  Oxidative Stress in Alzheimer’s Disease: Pathogenesis, Biomarkers and Therapy , 2011 .

[6]  C. Pérez,et al.  N-acylaminophenothiazines: neuroprotective agents displaying multifunctional activities for a potential treatment of Alzheimer's disease. , 2011, European journal of medicinal chemistry.

[7]  M. Carter,et al.  The Development of New Therapeutics for Alzheimer's Disease , 2010, Clinical pharmacology and therapeutics.

[8]  G. Hu,et al.  Angiogenin prevents serum withdrawal‐induced apoptosis of P19 embryonal carcinoma cells , 2010, The FEBS journal.

[9]  M. Pool,et al.  NeuriteTracer: A novel ImageJ plugin for automated quantification of neurite outgrowth , 2008, Journal of Neuroscience Methods.

[10]  D. Rai,et al.  Quercetin: A Versatile Flavonoid , 2007 .

[11]  S. Tanasupawat,et al.  Geldanamycin derivatives and neuroprotective effect on cultured P19-derived neurons. , 2007, Bioorganic & medicinal chemistry letters.

[12]  K. Komers,et al.  New Findings about Ellman’s Method to Determine Cholinesterase Activity , 2007, Zeitschrift fur Naturforschung. C, Journal of biosciences.

[13]  A. Cederbaum,et al.  Cycloheximide Protects HepG2 Cells from Serum Withdrawal-Induced Apoptosis by Decreasing p53 and Phosphorylated p53 Levels , 2006, Journal of Pharmacology and Experimental Therapeutics.

[14]  Francis C. Lau,et al.  The beneficial effects of fruit polyphenols on brain aging , 2005, Neurobiology of Aging.

[15]  N. Rakariyatham,et al.  Screening of antioxidant activity and antioxidant compounds of some edible plants of Thailand , 2005 .

[16]  L. Demirezer,et al.  Flavonol Glycosides from Asperula arvensis L. , 2005 .

[17]  D. Butterfield.  beta-Amyloid-associated free radical oxidative stress and neurotoxicity: implications for Alzheimer's disease. , 1997, Chemical research in toxicology.

[18]  H. Hatanaka,et al.  Survival factor-insensitive generation of reactive oxygen species induced by serum deprivation in neuronal cells , 1996, Brain Research.

[19]  M. McBurney,et al.  P19 Embryonal Carcinoma Cells: A Source of Cultured Neurons Amenable to Genetic Manipulation , 1995 .

[20]  M. McBurney,et al.  P19 embryonal carcinoma cells. , 1993, The International journal of developmental biology.

[21]  N. Roehm,et al.  An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. , 1991, Journal of immunological methods.

[22]  L S Freedman,et al.  Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. , 1978, Cancer research.

[23]  K. Courtney,et al.  A new and rapid colorimetric determination of acetylcholinesterase activity. , 1961, Biochemical pharmacology.

[24]  Veena,et al.  Anticholinesterase of essential oils and their constituents from Thai medicinal plants on purified and cellular enzymes , 2012 .

[25]  W. Marsden.  I and J , 2012 .

[26]  A. Saluja,et al.  ISOLATION OF STIGMASTEROL AND β­SITOSTEROL FROM PETROLEUM ETHER EXTRACT OF AERIAL PARTS OF AGERATUM CONYZOIDES (ASTERACEAE) , 2011 .

[27]  S. Mandel,et al.  Multifunctional neuroprotective derivatives of rasagiline as anti-alzheimer’s disease drugs , 2011, Neurotherapeutics.

[28]  N. Pai,et al.  Simultaneous isolation and identification of phytoconstituents from Terminalia chebula by preparative chromatography. , 2010 .

[29]  O. Pechanova,et al.  Neuroprotective Mechanisms of Natural Polyphenolic Compounds , 2010 .

[30]  H. J. Dorman,et al.  Plants as Potential Sources for Drug Development against Alzheimer ’ s Disease , 2009 .

[31]  J. Kilburn,et al.  Antimicrobial gallic acid from Caesalpinia mimosoides Lamk. , 2007 .

[32]  D. Banerjee,et al.  Cytotoxicity and Cell Growth Assays , 2006 .

[33]  D. Lamson,et al.  Antioxidants and Cancer III: Quercetin , 2001 .

[34]  C. Thiele.  Neuroblastoma Cell Lines , 1998 .

[35]  C. Berset,et al.  Use of a Free Radical Method to Evaluate Antioxidant Activity , 1995 .