Investigation of the mechanism of tanshinone IIA to improve cognitive function via synaptic plasticity in epileptic rats

Abstract

AbstractContext Tanshinone IIA is an extract of Salvia miltiorrhiza Bunge (Labiatae) used to treat cardiovascular disorders. It shows potential anticonvulsant and cognition-protective properties.Objective We investigated the mechanism of tanshinone IIA on antiepileptic and cognition-protective effects in the model of epileptic rats.Materials and methods Lithium chloride (LiCl)-pilocarpine-induced epileptic Wistar rats were randomly assigned to the following groups (n = 12): control (blank), model, sodium valproate (VPA, 189 mg/kg/d, positive control), tanshinone IIA low dose (TS IIA-L, 10 mg/kg/d), medium dose (TS IIA-M, 20 mg/kg/d) and high dose (TS IIA-H, 30 mg/kg/d). Then, epileptic behavioural observations, Morris water maze test, Timm staining, transmission electron microscopy, immunofluorescence staining, western blotting and RT-qPCR were measured.Results Compared with the model group, tanshinone IIA reduced the frequency and severity of seizures, improved cognitive impairment, and inhibited hippocampal mossy fibre sprouting score (TS IIA-M 1.50 ± 0.22, TS IIA-H 1.17 ± 0.31 vs. model 2.83 ± 0.31), as well as improved the ultrastructural disorder. Tanshinone IIA increased levels of synapse-associated proteins synaptophysin (SYN) and postsynaptic dense substance 95 (PSD-95) (SYN: TS IIA 28.82 ± 2.51, 33.18 ± 2.89, 37.29 ± 1.69 vs. model 20.23 ± 3.96; PSD-95: TS IIA 23.10 ± 0.91, 26.82 ± 1.41, 27.00 ± 0.80 vs. model 18.28 ± 1.01).Discussion and conclusions Tanshinone IIA shows antiepileptic and cognitive function-improving effects, primarily via regulating synaptic plasticity. This research generates a theoretical foundation for future research on potential clinical applications for tanshinone IIA.

Keywords

• Cognitive impairment
• epilepsy
• SYN
• PSD-95
• mossy fibre sprouting