Abstract

Objectives: This study investigated the neuroprotective effects of Jatrorrhizine in rat cortical neurons.

Method: The effects of Jatrorrhizine on hydrogen peroxide (H₂O₂)-induced cell lesion, levels of lipid peroxidation and antioxidant enzyme activities were investigated in rat cortical neurons. Levels of mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were measured by fluorescent rhodamine staining and 2’,7’-dichlorfluorescein-diacetate staining, respectively. ATP content was measured by a high performance liquid chromatography. The protein levels for Bax, Bcl2 and cleaved caspase-3 were analyzed by western blot protein expression.

Results: There was a significant reduction in cell viability and activities of Superoxide dismutase and glutathione peroxidase for the cortical neurons after exposure to 50μM H₂O₂ for 12h. The hydrogen peroxide increased the production of malondialdehyde and ROS but decreased MMP and ATP in the neurons. However, pretreatment with different concentrations of Jatrorrhizine (5-20μM) inhibited H₂O₂-induced neurotoxicity markedly. Jatrorrhizine also attenuated the H₂O₂-induced Bcl-2/Bax ratio reduction and caspase-3 activation in these neurons.

Conclusions: Our findings suggest that Jatrorrhizine plays a critical neuroprotective role in H₂O₂ - induced apoptosis through its anti-oxidative actions. This may allow Jatrorrhizine to be a novel therapeutic with its high bioavailability to treat Alzheimer’s disease.

Keywords: Alzheimer's disease, apoptosis, Hydrogen peroxide, Jatrorrhizine, oxidative stress, neurons.

Graphical Abstract