alloin and anthraquinone-sulfonate

Anthraquinone derivatives such as emodin have recently been shown to protect in models of beta amyloid β (Aβ) and tau aggregation-induced cell death. The mechanisms of action possibly involve preconditioning effects, anti-aggregation properties, and/or enhancing the phosphatidylinositol-3-kinase (PI3K)/AKT survival mechanism. We studied several natural (emodin, rhein, and aloin) and synthetic (AQ2S) anthraquinones, to screen for post-treatment therapeutic benefit in two models of neuronal death, namely hydrogen peroxide (H(2)O(2)) and staurosporine (STS)-induced injury. Treatment with emodin, rhein, or aloin failed to reduce H(2)O(2) injury. Moreover, consistent with emodin behaving like a mild toxin, it exacerbated oxidative injury at the highest concentration used (50 μM) in our post-treatment paradigm, and potently inhibited AKT. In contrast, AQ2S was neuroprotective. It reduced H(2)O(2) injury at 50 and 75 μM. In addition, AQ2S potently inhibited staurosporine (STS)-induced injury. The mechanisms of action involve caspase inhibition and AKT activation. However, blockade of AKT signaling with LY294002 failed to abolish AQ2S-mediated protection on the STS assay. This is the first study to report that AQ2S is a new neuroprotective compound and a novel caspase inhibitor.

Topics: Animals; Anthraquinones; Apoptosis; Caspases; Cell Survival; Cells, Cultured; Chromones; Emodin; Hydrogen Peroxide; Lipid Peroxidation; Morpholines; Neuroblastoma; Neurons; Neuroprotective Agents; Oxidative Stress; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Staurosporine