[Celastrol inhibits neurotoxicity induced by Cd].

Cadmium (Cd) is a common heavy metal in the environment. Cd may penetrate the blood-brain barrier and produce neurotoxicity, thus inducing various neurodegenerative diseases. Celastrol is an effective component of Hook. F., which has many pharmacological effects such as anti-cancer and anti-inflammatory. Here we explored the effect of celastrol on the corresponding neurotoxicity induced by Cd. Cell proliferation test, cell membrane integrity test, and cell morphology were observed to analyze the effect of Cd on the viability of HMC3. The neurotoxicity of Cd and the effect of celastrol on the corresponding neurotoxicity induced by Cd were analyzed by nitric oxide (NO) test, lipid peroxidation (MDA) test, and Western blotting. When the concentration of Cd reached 40 μmol/L, the inhibition rate of HMC3 cell proliferation was (57.17±8.23)% ( < 0.01, =5), compared with the control group. The cell activity continued to reduce when the Cd concentration further increased. When the concentration of Cd was higher than 40 μmol/L, the cell membrane of HMC3 was significantly damaged, and the damage was dose-dependent. Upon increasing the Cd concentration, the cell morphology began to change and the adhesion also became worse. Cd significantly increased the amount of NO released by HMC3 cells, while celastrol effectively inhibited the NO release of HMC3 cells induced by Cd. Cd greatly increased the release of MDA in HMC3 cells, and the level of MDA decreased rapidly upon the addition of 10 mol/L celastrol. Cd increased the expression of p-PI3K protein, and the levels of p-PI3K protein and p-AKT protein were inhibited by the addition of celastrol (10 mol/L, 10 mol/L), thus preventing cell apoptosis. In conclusion, celastrol inhibits Cd induced microglial cytotoxicity and plays a neuroprotective role.