ABSTRACT
BACKGROUND: When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis. PURPOSE: The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (H2O2)-induced injury in SH-SY5Y cells in vitro. METHODS: SH-SY5Y cells were simultaneously treated with AU and H2O2 for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry. RESULTS: The results showed that AU can significantly increase the H2O2-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that H2O2 stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In H2O2-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways. CONCLUSION: These results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways.
Subject(s)
Gene Expression Regulation, Neoplastic/drug effects , Heme Oxygenase-1/metabolism , Hydrogen Peroxide/toxicity , Iridoid Glucosides/pharmacology , NF-E2-Related Factor 2/metabolism , Neuroprotective Agents/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , Genes, bcl-2/genetics , Genes, bcl-2/physiology , Heme Oxygenase-1/genetics , Humans , Mitogen-Activated Protein Kinase Kinases/genetics , Mitogen-Activated Protein Kinase Kinases/metabolism , NF-E2-Related Factor 2/genetics , NF-kappa B/metabolism , Neuroblastoma , Oxidation-Reduction , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolismABSTRACT
OBJECTIVE: To study the chemical constituents of Ligularia macrophylla. METHODS: Isolation and purification were carried out on repeated silica gel column chromatography. The structures of the compounds were identified by physico-chemical properties and spectral analyses. RESULTS: Eight compounds were isolated and identified as kaempferol (1), 2,4'-dihydroxy-5-methoxychalcone (2), 5-hydroxy-3,4', 7-trimethoxyflavone (3), isobutyl ester terephthalic acid (4), 4-hydroxybenzaldehyde (5), mono (2-ethylhexyl) terephthalate (6), lupeol (7), beta-sitosterol (8). CONCLUSION: Compounds 1 - 7 are isolated from this plant for the first time.