chlorogenic-acid and Neuroblastoma

1,3,5-Tri-

Topics: Annexin A5; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Cytochromes c; Humans; Hydrogen Peroxide; Lactate Dehydrogenases; Malondialdehyde; Mitogen-Activated Protein Kinases; Neuroblastoma; Phosphorylation; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Quinic Acid; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase

Oxidative stress has been confirmed as a contribution to the pathogenesis and pathophysiology of many neurological disorders such as Alzheimer's disease and Parkinson's disease. Caffeoylquinic acids (CQAs) are considered to have anti-oxidative stress ability in a previous study, but the structure-activity relationships (SARs) of CQAs in neuroprotective effects are still unclear. In the present study, we primarily expound the SARs of CQAs in counteracting H

Topics: Apoptosis; Cell Line, Tumor; Extracellular Signal-Regulated MAP Kinases; Glutathione Peroxidase; Humans; Hydrogen Peroxide; Malondialdehyde; Membrane Potential, Mitochondrial; Neuroblastoma; Neuroprotection; Neuroprotective Agents; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Quinic Acid; Superoxide Dismutase

Compound MQA (1,5-O-dicaffeoyl-3-O-[4-malic acid methyl ester]-quinic acid) is a natural caffeoylquinic acid derivative isolated from Arctium lappa L. roots. This study aims to explore the neuroprotective effects of MQA against hydrogen peroxide (H

Topics: Annexin A5; Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Chlorogenic Acid; Cyclin D1; Cytochromes c; Dose-Response Relationship, Drug; Humans; Hydrogen Peroxide; L-Lactate Dehydrogenase; Malondialdehyde; Membrane Potential, Mitochondrial; Neuroblastoma; Neuroprotective Agents; Oxidants; Oxidative Stress; Quinic Acid; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase

The accumulation of amyloid-β (Aβ) is a hallmark of Alzheimer's disease and is known to result in neurotoxicity both in vivo and in vitro. We previously demonstrated that treatment with the water extract of Centella asiatica (CAW) improves learning and memory deficits in Tg2576 mice, an animal model of Aβ accumulation. However the active compounds in CAW remain unknown. Here we used two in vitro models of Aβ toxicity to confirm this neuroprotective effect and identify several active constituents of the CAW extract. CAW reduced Aβ-induced cell death and attenuated Aβ-induced changes in tau expression and phosphorylation in both the MC65 and SH-SY5Y neuroblastoma cell lines. We confirmed and quantified the presence of several mono- and dicaffeoylquinic acids (CQAs) in CAW using chromatographic separation coupled to mass spectrometry and ultraviolet spectroscopy. Multiple dicaffeoylquinic acids showed efficacy in protecting MC65 cells against Aβ-induced cytotoxicity. Isochlorogenic acid A and 1,5-dicaffeoylquinic acid were found to be the most abundant CQAs in CAW, and the most active in protecting MC65 cells from Aβ-induced cell death. Both compounds showed neuroprotective activity in MC65 and SH-SY5Y cells at concentrations comparable to their levels in CAW. Each compound not only mitigated Aβ-induced cell death, but was able to attenuate Aβ-induced alterations in tau expression and phosphorylation in both cell lines, as seen with CAW. These data suggest that CQAs are active neuroprotective components in CAW, and therefore are important markers for future studies on CAW standardization, bioavailability, and dosing.

Topics: Amyloid beta-Peptides; Cell Death; Cell Line, Transformed; Centella; Chlorogenic Acid; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic; Humans; Neuroblastoma; Neuroprotective Agents; Quinic Acid; tau Proteins

This in vitro investigation was designed to examine potential neuroprotection by dicaffeoylquinic acids (diCQAs) extracted from a traditional Chinese medicinal herb herba erigerontis and their effects against the toxicity induced by β-amyloid peptide (Aβ25-35 ).. The neuroblastoma SH-SY5Y cell line was treated with Aβ or 3, 4-diCQA, 3, 5-diCQA or 4, 5-diCQA. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction was assayed by spectrophotometrical method, lipid peroxidation (malondialdehyde) on the basis of the level of thiobarbituric acid-reactive substance, the activity of superoxide dismutase by the xanthine oxidase procedure, the frequency of apoptosis by flow cytometry, and the levels of α3 and α7 nicotinic acetylcholine receptor (nAChR) subunit proteins by Western blotting.. When the cells were exposed to Aβ25-35 , MTT reduction declined, oxidative stress and apoptosis were enhanced, and the expression of α3 and α7 nAChR subunit proteins was lowered. Expression of the α7 nAChR subunit protein was increased by all three diCQAs, and the level of α3 was increased by 3, 5-diCQA and 4, 5-diCQA. Significantly, pretreatment with diCQAs attenuated the neurotoxic effects of Aβ25-35 , a neuroprotective effect in which the upregulation of α7 and α3 nAChR may be involved.. The diCQAs exert a protective effect on Aβ-induced neurotoxicity in SH-SY5Y cells and a potential underlying mechanism involving stimulation of nAChRs.

Topics: Amyloid beta-Peptides; Apoptosis; Cell Line, Tumor; Humans; Lipid Peroxidation; Neuroblastoma; Neuroprotective Agents; Oxidative Stress; Quinic Acid; Reactive Oxygen Species; Receptors, Nicotinic; Superoxide Dismutase