Eupatilin inhibits microglia activation and attenuates brain injury in intracerebral hemorrhage.

Inflammation serves a critical role in the pathophysiology of intracerebral hemorrhage (ICH)-induced brain injury. Eupatilin, a pharmacologically active flavone derived from Artemisia sp., has been reported to have antioxidant, anti-inflammatory, anti-allergic and antitumor activities. However, the effect of eupatilin in ICH has not been well studied. The aim of the present study was to investigate the effect of eupatilin on ICH-induced microglial inflammation. The MTT and Transwell migration assay results revealed that eupatilin significantly inhibited microglial migration. It also decreased the production of inflammatory cytokines in erythrocyte lysis-induced BV2 cells, as well as the level of intracellular reactive oxygen species. The anti-inflammatory mechanism of eupatilin was also investigated using ELISAs and western blotting and the results demonstrated that eupatilin was able to inhibit erythrocyte lysis-induced NF-κB activation in BV2 cells. Taken together, the results of the present study suggest that eupatilin serves neurological protective effects via inhibiting microglial inflammation, providing an experimental basis for the use of eupatilin as a therapeutic target for ICH.

The effects of interleukin 2 and rAd-p53 as a treatment for glioblastoma.

Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell propagation, triggering innate and adaptive immunity. IL-2 has been used for cancer therapy and has achieved curative effects. Recombinant adenovirus p53 injection (rAd­p53) is a gene therapeutic agent that may improve the prognosis of patients with glioblastoma (GBM). In the present study, the effect of combined IL­2 and rAd­p53 treatment was studied. The ability of IL­2 to stimulate immunoregulation and the ability of p53 to induce apoptosis for GBM was researched in the GBM tumor model. In addition, the activity of IL­2 was analyzed. The antitumor potential of IL­2 and rAd­p53 was studied using xenograph mice carrying GBM cells. Tumor­specific CD4+ and CD8+ T cells were also analyzed in the GBM­bearing models. The results demonstrated that IL­2 and rAd­p53 not only stimulated tumor­specific cytotoxic T­lymphocyte responses and increased regulatory CD4+ and cytotoxic CD8+ T cell proliferation, however additionally increased expression of apoptosis­associated genes. The treatment with IL­2 and rAd­p53 resulted in tumor regression and prolonged the survival of glioma­bearing mice. Taken together, a combination of IL­2 and rAd­p53 treatment combines the effects of immunotherapy and oncolytic therapy and may be a comprehensive therapeutic schedule for clinical application in future cancer therapies.

Overexpression of GRP75 inhibits inflammation in a rat model of intracerebral hemorrhage.

Glucose­regulated protein 75 (GRP75) is a member of the heat shock protein 70 family and previous studies have demonstrated that GRP75 is involved in diseases of the central nervous system. However, the biological function of GRP75 in intracerebral hemorrhage (ICH) remains to be clarified. Thus, the aim of the present study was to evaluate the effects of GRP75 in a rat model of ICH. Western blotting was used to detect the protein expression of GRP75, active caspase­3, Bax, Bcl­2, p­Akt and Akt in brain tissues following ICH. The levels of tumor necrosis factor­α (TNF­α) and interleukin (IL)­1ß were evaluated using ELISA assay. Expression of GRP75 mRNA and protein was demonstrated to be reduced in the brain tissues of rats with ICH compared with sham­operated rats. In addition, overexpression of GRP75 in brain tissues with ICH significantly inhibited the production of the inflammatory cytokines TNF­α and IL-1ß and increased Bcl­2/decreased Bax levels compared with ICH alone. Furthermore, overexpression of GRP75 in brain tissues with ICH resulted in significantly increased phosphorylation of Akt compared with ICH alone. Therefore, the present study demonstrated, for the first time to the best of our knowledge, significantly reduced GRP75 expression in brain tissues following ICH, and that overexpression of GRP75 inhibits inflammation and potentially inhibits neuronal apoptosis in a rat model of ICH. GRP75 may, therefore, represent a promising target in the treatment of ICH.