Neuroprotective Capabilities of Tanshinone IIA against Cerebral Ischemia/Reperfusion Injury via Anti-apoptotic Pathway in Rats

Abstract

Danshen, derived from the dried root or rhizome of Salviae miltiorrhizae BGE., has Tanshinone IIA (TSA) as one of its active ingredients. Recent reports have shown that TSA can inhibit the apoptosis induced by serum withdrawal or ethanol in cultured PC12 cells. However, whether TSA has any neuroprotective effect remains unknown. In this study, we investigated the effects of TSA on cerebral apoptosis induced by middle cerebral artery occlusion (MCAO) in which cerebral ischemia had been induced 2 h earlier. Twenty-four hours after reperfusion, the rats were assessed for infarct volume etc. Intraperitoneal administration of 25 and 40 mg/kg TSA 10 min after MCAO significantly diminished infarct volume and brain water content and improved neurological deficits in a dose-dependent manner. The 25 mg/kg dosage was more effective. Treatment with 25 mg/kg TSA significantly improved symptoms and reduce infarct volume at different points in time, of which 10 min after MCAO was the most significant. Nissl-staining and HE-staining of the 25 mg/kg TSA group were more appreciable in terms of improvement relative to the vehicle group in the infarct core. TSA of dosage 25 mg/kg significantly decreased the expression of cleaved caspase-3 protein and increased the expression of B-cell lymphoma 2 (bcl-2) protein in the ischemic cortex. Fewer terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL)-positive cells were found in the penumbra of the treated group, but they were significantly more common in the vehicle group. We here conclude that the neuroprotective effects of TSA against focal cerebral ischemic/reperfusion injury are likely to be related to the attenuation of apoptosis.

Tanshinone IIA pretreatment attenuates ischemia/reperfusion-induced renal injury

“…The present results indicate that tanshinone IIA pretreatment normalizes markers of renal function, and reduced BUN and creatinine levels in the I/RIRI-induced rats. These findings are consistent with previous results demonstrating that tanshinone IIA attenuates hepatic (21) and cerebral ischemia/reperfusion injury (14). MPO primarily exists in the azurophilic granule of neutrophile granulocytes.…”

“…In China, S. miltiorrhiza has been widely applied in the treatment of cardiovascular and cerebrovascular diseases (13). Tanshinone IIA is a key active monomer extracted from S. miltiorrhiza (14). Previous studies suggest that pre-treatment tanshinone IIA exerts a nerve protective effect against cerebral ischemia reperfusion injury (14,15).…”

“…Tanshinone IIA is a key active monomer extracted from S. miltiorrhiza (14). Previous studies suggest that pre-treatment tanshinone IIA exerts a nerve protective effect against cerebral ischemia reperfusion injury (14,15). The protection mechanism may involve B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and TRPM7 regulation (16,17).…”

Effects of Salvia miltiorrhiza on CNS Neuronal Injury and Degeneration: A Plausible Complementary Role of Tanshinones and Depsides

“…Chen and coworkers [37] showed that TSIIA treatment reduced the number of degenerated neurons, significantly (p < 0.05) increased the number of intact neurons, and inhibited cerebral apoptosis determined by TUNEL staining [37]. TSIIA decreased the expression of caspase-3 and caspase-8 and these results were proportional to the dose of TSIIA used [27].…”

Targeting ONOO^-/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment

“…The structure of tanshinone IIA is shown in figure 7. Tanshinone IIA demonstrated an antiapoptotic effect via upregulating blc-2 expression and downregulating active caspase-3 in the cortex, subsequently reducing neural apoptosis, decreasing the brain infarct volume and attenuating neurological deficit in a rat MCAO model [207,208]. In addition, tanshinone IIA scavenged RNS in an ischemic stroke model [209].…”