Cadmium (Cd) is a common heavy metal in the environment. Cd2+ may penetrate the blood-brain barrier and produce neurotoxicity, thus inducing various neurodegenerative diseases. Celastrol is an effective component of Tripterygium wilfordii 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 Cd2+. Cell proliferation test, cell membrane integrity test, and cell morphology were observed to analyze the effect of Cd2+ on the viability of HMC3. The neurotoxicity of Cd2+ and the effect of celastrol on the corresponding neurotoxicity induced by Cd2+ were analyzed by nitric oxide (NO) test, lipid peroxidation (MDA) test, and Western blotting. When the concentration of Cd2+ reached 40 μmol/L, the inhibition rate of HMC3 cell proliferation was (57.17±8.23)% (P < 0.01, n=5), compared with the control group. The cell activity continued to reduce when the Cd2+ concentration further increased. When the concentration of Cd2+ was higher than 40 μmol/L, the cell membrane of HMC3 was significantly damaged, and the damage was dose-dependent. Upon increasing the Cd2+ concentration, the cell morphology began to change and the adhesion also became worse. Cd2+ significantly increased the amount of NO released by HMC3 cells, while celastrol effectively inhibited the NO release of HMC3 cells induced by Cd2+. Cd2+ greatly increased the release of MDA in HMC3 cells, and the level of MDA decreased rapidly upon the addition of 10-7 mol/L celastrol. Cd2+ 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 (10‒7 mol/L, 10‒6 mol/L), thus preventing cell apoptosis. In conclusion, celastrol inhibits Cd2+ induced microglial cytotoxicity and plays a neuroprotective role.
Keywords: Cd2+; celastrol; microglia; neuroprotection; neurotoxicity.