ABSTRACT
Traumatic brain injury (TBI) is a common disease associated with a high rate of morbidity and mortality. Secondary brain injury following TBI triggers pathological, physiological, and biological reactions that lead to neurological dysfunctions. Alantolactone (ATL) is a well-known Chinese medicine that possesses strong anti-inflammatory properties, but its role in TBI remains poorly understood. The objective of this study was to evaluate the protective effect of ATL in a rat model of controlled cortical impact (CCI). We observed the neurological scores, brain water content, oxidative stress, neuroinflammation and apoptosis by performing an enzyme-linked immunosorbent assay, western blotting, quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemical (IHC) staining and other methods after CCI. The neurological scores, brain water content, levels of oxidative stress and inflammatory cytokines, and apoptosis index were markedly decreased following the ATL treatment in rats after TBI. Moreover, the antioxidant and anti-inflammatory effects of ATL in TBI may be partially mediated by inhibition of the NF-κB pathway and suppression of Cyclooxygenase 2 (COX-2). In addition, ATL attenuated TBI-induced neuronal apoptosis by suppressing the cytochrome c/caspase-dependent apoptotic pathway. Thus, ATL could exert neuroprotection in rats in a TBI model. Importantly, ATL has great potential in the clinical treatment of TBI.
ABSTRACT
The global burden of malignant glioma is expected to increase and new therapy approaches are urgently required. Solasonine is a natural glycoalkaloid compound that has been used in cancer treatment for many years; however the precise mechanisms are poorly understood. Here we seek to explore the potential roles of solasonine in glioma that could add to the development of newer therapeutic approaches for the treatment of malignant glioma. Cell proliferation of glioma cells was determined by MTT assay, and the biological functions of solasonine were investigated by migration, colony formation, apoptosis assays and cell cycle analysis in glioma cells. Western blotting and RT-qPCR were used to detect the protein and gene expression levels respectively. The nuclear localization of NF-κB p50/p65 was analyzed after treatment with solasonine. The roles of MAPKs in the anticancer effect of solasonine were then examined. The in vivo anti-tumor efficacy of dopamine was also analyzed in xenografts nude mice. We report that solasonine could inhibit cell proliferation, migration and colony formation of glioma cells. Treatment of solasonine induced apoptosis via modulating cytochrome c and caspase signaling. Besides, solasonine decreased the expression of proinflammatory mediators and nuclear translocalization of NF-κB p50/p65. Mechanistic investigation further revealed that solasonine may target anti-inflammatory signaling pathway, and more specifically p-p38 and p-JNK MAPKs. All these indicated that solasonine could inhibit glioma growth via inhibiting inflammatory signaling pathway.
