ABSTRACT
BACKGROUND Chlorogenic acid (CGA), a dietary polyphenol derived from many plants, has been previously reported to exert neuroprotective properties. However, its pharmacological role in Parkinson's disease (PD) and the underlying mechanisms are unclear. MATERIAL AND METHODS In the present study, we investigated the beneficial effects of CGA against the toxicity of 6-hydroxydopamine (6-OHDA) in animal and cellular models. One week after 6-OHDA administration, the behavioral activities of rats were determined by rotarod test and apomorphine-induced rotational test. The viability and apoptosis of SH-SY5Y cells following 6-OHDA exposure were determined by MTT assay and annexin V-FITC/PI double staining, respectively. The activities of antioxidant enzymes in the rat striatal tissues and SH-SY5Y cells were detected by ELISA. RESULTS The results demonstrated that 6-OHDA-induced PD-like behavioral impairments of rats were significantly forestalled by CGA administration. The increased apoptosis and reduced activities of antioxidant enzymes in the striatum of 6-OHDA-lesioned rats were also attenuated by CGA. Moreover, in an in vitro experiment, the impaired viability and enhanced apoptosis of 6-OHDA-injured SH-SY5Y cells were significantly restored by CGA pretreatment. In addition, CGA also obstructed 6-OHDA-induced ROS production and endoplasmic reticulum (ER) stress in SH-SY5Y cells. CONCLUSIONS Taken together, these data show that CGA might be an effective neuroprotective compound that mitigates oxidative stress and ER stress in PD.
Subject(s)
Chlorogenic Acid/therapeutic use , Endoplasmic Reticulum Stress/drug effects , Animals , Antioxidants/pharmacology , Apoptosis/drug effects , Cell Death/drug effects , Cell Line, Tumor , Cell Survival/drug effects , China , Chlorogenic Acid/pharmacology , Humans , Male , Neurons/drug effects , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Oxidopamine/adverse effects , Rats , Rats, Sprague-Dawley , Reactive Oxygen SpeciesABSTRACT
The present study aimed to investigate changes in the expression of interleukin (IL)-1 receptor-associated kinase 4 (IRAK4) and microRNA (miRNA or miR)-93 in mice with cerebral ischemia reperfusion (CIR) injury, as well as the association and regulatory mechanism between IRAK4 and miR-93. The CIR mouse model was constructed and mouse microglia BV2 cells were transfected with miR-93 mimic or miR-93 inhibitor. Quantitative polymerase chain reaction was used to measure the expression of mRNA and miR-93. Western blotting was performed to determine protein expression. Enzyme-linked immunosorbent assays were performed to measure the concentrations pro-inflammatory factors. The expression of miR-93 in CIR mice brains was significantly reduced, while Ago-miR-93 (a type of miRNA analog) increased its expression. Ago-miR-93 alleviated neurological deficits and reduced cerebral infarction volume in the mice. Furthermore, Ago-miR-93 inhibited inflammatory responses following CIR. Ago-miR-93 decreased the rate of cell apoptosis following CIR. In addition, miR-93 downregulated IRAK4 protein expression, but did not alter its mRNA expression levels in BV2 cells. miR-93 expression reduced the expression of pro-inflammatory factors in BV2 cells. Ago-miR-93 inhibited IRAK4 expression in the brain tissues of CIR mice. The present study demonstrated that miR-93 inhibits inflammatory responses and cell apoptosis following CIR by targeting the IRAK4 signaling pathway.