Neuroprotective effect and underlying mechanism of sodium danshensu [3-(3,4-dihydroxyphenyl) lactic acid from Radix and Rhizoma Salviae miltiorrhizae = Danshen] against cerebral ischemia and reperfusion injury in rats

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

“…TSIIA decreased the expression of caspase-3 and caspase-8 and these results were proportional to the dose of TSIIA used [27]. TSAII reduced the Aβ [25][26][27][28][29][30][31][32][33][34][35] -induced increase of caspase-3 activity and reduced the cytochrome C translocation into cytosol from mitochondria, protecting it from mitochondrial abnormalities [27]. In addition, TSIIA increased the expression of Bcl-2 in the ischemic cortex in TSIIA-treated ischemia groups and prevented an increase in the Bax/Bcl-2 ratio induced by neuronal damage [38].…”

“…The nanoparticles effectively reduced infarction volume, neurological dysfunctions, neutrophils infiltration, and neuronal apoptosis. Similar models of CNS trauma have been investigated with hydrophilic depsides, which are administered intravenously [28][29][30] or orally [31][32][33][34]. Similar doses were used by i. v. administration or per os (10-60 mg/kg), with all the cases having positive outcomes and, also, lower dosages.…”

“…From the above results, the fact that such different compounds having remarkable different structures, sizes, and polarity can act in the same way in CNS neuronal injury and degeneration it is quite extraordinary. Additionally, it is noteworthy that SalB [30,[32][33][34], a tetramer of caffeic acid, caffeic acid dimer [29], and the smaller analog danshensu (3,4-dihydroxyphenyllactic acid) [28,31] …”

“…Shi and coworkers [40] elucidated the neuroprotective effects of TSAII against Aβ [25][26][27][28][29][30][31][32][33][34][35] -induced cytotoxicity and detected the association of this protective effect with calpain and the p35/Cdk5 pathway. TSAII increased the viability of neurons, decreased the expression of phosphorylated tau in neurons induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] , maintained the normal expression of p35 on peripheral membranes, and decreased p25 expression in the cytoplasm. TanIIA also inhibited the translocation of Cdk5 from the nucleus into the cytoplasm of primary neurons induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] .…”

“…Wang and coworkers [22] substantiated the anti-inflammatory properties of TSAII in cerebral ischemia through the downregulation of HMGB1, the translocation from the nucleus to the cytoplasm of RAGE, TLR4, and NF-κB, and the upregulation claudin-5 expression. Moreover, exposure of cortical neurons to 30 µM Aβ [25][26][27][28][29][30][31][32][33][34][35] caused decreased activities of SOD and GSH-Px as well as increased levels of MDA production, while the pretreatment with TSAII attenuated the changes in SOD, GSH-Px, and MDA induced by the treatment of Aβ [25][26][27][28][29][30][31][32][33][34][35] [24]. Tang and coworkers [25] reported that the mRNA expression levels of Trx-1 and Trx-2 around the ischemia area were significantly increased (p < 0.05) in a brain transient ischemia model created by the blockage of the middle cerebral artery.…”