Tanshinone IIA Attenuates Cognitive Impairment in Rats via Improving Mitochondrial Function and Oxidative Stress

Chronic cerebral hypoperfusion (CCH) is one of the most important causes in the initiation and progression of vascular dementia. Tanshinone IIA (TSA) is an active compound isolated from the plant roots of Salvia Miltiorrhiza, which is a traditional Chinese medicine with the activities of improving blood circulation and reducing vessel stasis. In this study, the potential neuroprotective effects and mechanisms of TSA were studied using a bilateral common carotid artery occlusion (BCCAO) model in vivo and H₂O₂ induced oxidative damage of primary astrocytes in vitro. The results showed that TSA obviously reversed the BCCAO induced cognitive impairment in rats evaluated by Morris water maze (MWM). Nissl staining showed the neuronal loss in CA1 and CA3 region were reversed by TSA. TSA also increased the expression of brain-derived neurotrophic factor (BDNF) levels in cortex and hippocampus. In H₂O₂-induced primary astrocytes injury, TSA suppressed the decrease of cell viability and inhibited lactate dehydrogenase (LDH) release. TSA attenuated mitochondrial membrane potential (MMP) loss and increased ATP level. Furthermore, TSA significantly reversed the damage induced by the disorders of the mitochondria respiratory complex enzyme, and then attenuated reactive oxygen species (ROS) accumulation and lipid peroxidation, simultaneously enhanced antioxidant capacity. The results demonstrated that TSA could enhance mitochondrial bioenergetics and ameliorate oxidative stress effectively, which might contribute to the improving effect of TSA on cerebral ischemia, hypoperfusion and oxidative injuries. Our study provided a new evidence to illustrate the mechanisms of protective effects of TSA on cerebral ischemia induced cognitive impairment.