Mitigation of acute radiation-induced brain injury in a mouse model using anlotinib.

BACKGROUND: With the development of radiological technologies, radiotherapy has been gradually widely used in the clinic to intracranial tumours and become standardised. However, the related central nervous system disorders are still the most obvious complications after radiotherapy. This study aims to quantify the effectiveness of anlotinib, a small molecule inhibitor of multiple receptor tyrosine kinases, in mitigating acute phase of radiation-induced brain injury (RBI) in a mouse model. METHODS: The onset and progression of RBI were investigated in vivo. All mice, (except for the sham group) were irradiated at a single-fraction of 20 Gy and treated with different doses of anlotinib (0, 0.2 and 0.8 mg/kg, respectively). The expression levels of glial fibrillary acidic protein (GFAP), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2) were assessed by western blot. Histological changes were identified by luxol fast blue (LFB) staining. RESULTS: The expression levels of GFAP, HIF-1α, and VEGF were downregulated following treatment with anlotinib. However, anlotinib failed to inhibit the development of demyelination. Cerebral edema [as measured by brain water content (BWC)] was also mitigated following treatment with anlotinib. CONCLUSIONS: In summary, treatment with anlotinib significantly mitigated the adverse effects of acute RBI in a dose-dependent manner by downregulating the activation of astrocytes, improving brain hypoxia, and alleviating cerebral edema.

1,n-Rearrangement of allylic alcohols promoted by hot water: application to the synthesis of navenone B, a polyene natural product.

It was reported for the first time that hot water as a mildly acidic catalyst efficiently promoted 1,n-rearrangement (n = 3, 5, 7, 9) of allylic alcohols. In some cases, the rearrangement reactions joined isolated C-C double or triple bonds to generate conjugated polyene or enyne structure motifs. We used the 1,3-rearrangement reaction of an allylic alcohol in hot water as part of an attractive new strategy for construction of the polyene natural product navenone B by iterative use of a Grignard reaction, a 1,3-rearrangement of the resulting allylic alcohol, and subsequent oxidation of the rearranged product.