Potassium 2-(l-hydroxypentyl)-benzoate attenuates neuroinflammatory responses and upregulates heme oxygenase-1 in systemic lipopolysaccharide-induced inflammation in mice

A neuroinflammatory response is commonly involved in the progression of many neurodegenerative diseases. Potassium 2-(1-hydroxypentyl)-benzoate (PHPB), a novel neuroprotective compound, has shown promising effects in the treatment of ischemic stroke and Alzheimer׳s disease (AD). In the present study, the anti-inflammatory effects of PHPB were investigated in the plasma and brain of C57BL/6 mice administered a single intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). Levels of iNOS and the cytokines TNF, IL-1and IL-10 were elevated in plasma, cerebral cortex and hippocampus after LPS injection and the number of microglia and astrocytes in cortex and hippocampus were increased. LPS also upregulated the expression of heme oxygenase-1 (HO-1) in the cortex and hippocampus. PHPB reduced the levels of iNOS and cytokines in the plasma and brain, decreased the number of microglia and astrocytes and further enhanced the upregulation of HO-1. In addition, PHPB inhibited the LPS-induced phosphorylation of ERK, P38 and JNK. These results suggest that PHPB is a potential candidate in the treatment of neurodegenerative diseases through inhibiting neuroinflammation.

EFFECTS OF INSULIN-LIKE GROWTH FACTOR 1 ON β-AMYLOID INDUCED NEURON APOPTOSIS AND TAU PHOSPHORYLATION / 神经解剖学杂志

The aim of this study is to elucidate the protective and anti-apoptotic effects of insulin-like growth factor 1 ( IGF-1 ) against β-amyloid (Aβ) and investigate the effect of IGF-1 on Aβ-induced tau phosphorylation. Cell viability was measured using the MTT (3-(4,5-dimethylthiazolyl-2 )-2,5-diphenyltetrazolium bromide) assay, early apoptosis and late apoptosis/necrosis were analyzed by flow cytometry using Annexin V-FITC and propidium iodide (PI) double staining, and morphology was examined by Hoechst 33342 staining. Tau phosphorylation was detected using AT8 immunostaining. Preincubation of cultured rat hippocampal neurons with IGF-1 for 24 h prevented cytotoxicity induced by Aβ25-35 for 48 h. The MTT value significantly increased from 54.51% to 61.8% of the control group, and the percentage of Hoechst 33342-positive cells decreased from 30.77% to 22.81%. Incubation with Aβ25-35 for 48 h caused a marked increase in the percentages of Annexin V-FITC single-labeled cells (Annexin V +/PI-) and Annexin V/PI double-stained cells (Annexin V +/PI + ) (3.41% and 19.47% , respectively), which were significantly decreased by pretreatment with 100 ng/ml of IGF-1 for 24 h (to 2.98% and 15.16% , respectively). Aβ25-35 treatment increased tau phosphorylation and AT8 positive cells were 41.84%. This effect could be inhibited by different concentrations of IGF-1. Our findings showed that IGF-1 protected against Aβ-induced cytotoxicity, decreased the percentage of early and late apoptosis/necrosis cells, and inhibited tau phosphorylation, which may be the cellular mechanisms for its neuroprotective action.