Polydatin inhibits LPS-induced inflammatory response in BV2 microglia by disrupting the formation of lipid rafts.

OBJECTIVE: Polydatin has been used in the treatment of various inflammatory diseases. However, its role in the regulation of neuroinflammation has not been reported. In this study, we designed to investigate the anti-inflammatory effects of polydatin in LPS-stimulated BV2 microglia cells. METHODS: Inflammatory mediators TNF-α, IL-1ß, NO, and PGE2 production were measured by ELISA. The protein of signaling pathways were detected by western blot analysis. RESULTS: The results showed that polydatin significantly ameliorated the production of TNF-α, IL-1ß, NO, and PGE2 up-regulated by LPS. Polydatin also blocked LPS-induced NF-κB activation. In addition, PI3K and AKT, the up-stream molecules of NF-κB signaling pathway, were inhibited by the treatment of polydatin. Also, we found the formation of lipid rafts was inhibited by polydatin through attenuating the cholesterol content. Finally, polydatin was found to increase the expression of ABCA1 and ABCG1. CONCLUSION: In conclusion, the results of the present study suggested that polydatin exhibited its anti-inflammatory effects in BV2 cells through disrupting lipid rafts, which subsequently inhibiting PI3K/AKT signaling pathway.

Mitochondrial biogenesis in neurodegeneration.

Mitochondria play a key role in energy production, calcium homeostasis, cell survival, and death. Adverse stimulations including neurodegenerative diseases may result in mitochondrial dynamic imbalance, free radical production, calcium accumulation, intrinsic cell death pathway activation and eventually cell death. Therefore, preserving or promoting mitochondrial function is a potential therapeutic target for the treatment of neurodegenerative disorders. Mitochondrial biogenesis is a process by which new mitochondria are produced from existing mitochondria. This biogenesis process is regulated by Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1alpha (PGC-1α). Once being activated by either phosphorylation or de-acetylation, PGC-1α activates nuclear respiratory factor 1 and 2 (NRF1 and NRF2), and subsequently mitochondrial transcription factor A (Tfam). The activation of this PGC-1α - NRF -Tfam pathway leads to synthesis of mitochondrial DNA and proteins and generation of new mitochondria. © 2017 Wiley Periodicals, Inc.

Deregulated expression of the Per1 and Per2 in human gliomas.

BACKGROUND: Growing evidence shows that the deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of genes controlling circadian rhythm in glioma cells have not been explored. METHODS: Using reverse transcription polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important clock genes, Per1 and Per2, in 33 gliomas. RESULTS: In this study, out of 33 gliomas, 28 were Per1-positive, and 23 were Per2-positive. The expression levels of Per1 and Per2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of Per1 and Per2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was insignificant (P>0.05). While there was no difference in the intensity of immunoactivity for Per2 between high-grade gliomas and low-grade gliomas (r=-0.330, P=0.061), the expression level of Per1 in high-grade gliomas was significantly lower than that in low-grade gliomas(r=-0.433, P=0.012). CONCLUSIONS: In this study, we found that the expression of Per1 and Per2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in Per1 and Per2 expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells. Differential expression of circadian clock genes in glioma and non-glioma cells may provide a molecular basis for the chemotherapy of gliomas.