Partial Neuroprotective Effect of Pretreatment with Tanshinone IIA on Neonatal Hypoxia-Ischemia Brain Damage

Abstract

Tanshinone IIA is a compound purified from the Chinese herb Danshen (Radix Salviae Miltiorrhiza Bge). The neuroprotective effect of tanshinone IIA was investigated in a neonatal rat model of hypoxia-ischemia brain damage. Hypoxia-ischemia encephalopathy was induced in rats at day 7 of postnatal age by ligation of the right common carotid artery, followed by 2 h of hypoxia. Tanshinone IIA (10 mg/kg, i.p.) was injected daily from day 2 before surgery for 9 or 16 d. Our results demonstrated significant and sustained brain damage in the hypoxia-ischemia-and vehicle-treated groups at 1 and 3 wk after surgery. Treatment with tanshinone IIA significantly reduced the severity of brain injury, as indicated by the increase in ipsilateral brain weight and neuron density, compared with those of sham-operated animals. The recovery of sensorimotor function and histology was observed in animals that received tanshinone IIA. The plasma of tanshinone IIA-treated rats exhibited higher antioxidant activities, as reflected by the oxygen radical absorbance capacity assay, compared with the vehicle-treated rats. In the neural progenitor cell line C17.2 that was subjected to 2,2'-azobis (2-amidino propane hydrochloride)-induced oxidative stress, tanshinone IIA increased cell viability and protected against mitochondrial damage (JC-1 assay). Our results suggest that tanshinone IIA has antioxidative activities and that treatment that is started before a hypoxic-ischemic insult is partially neuroprotective. Further studies are required to elucidate whether rescue treatment with tanshinone IIA is effective and to determine whether its protective effect is also associated with secondary cooling of the brain. Abbreviations AAPH, 2,2'-azobis (2-amidino propane hydrochloride) AchE, acetylcholinesterase HIE, hypoxia-ischemia encephalopathy MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide NSE, neuron-specific enolase ORAC, oxygen radical absorbance capacity Hypoxia-ischemia encephalopathy (HIE) in the newborn infant is a major cause of acute mortality and chronic neurologic disability in survivors. During hypoxic-ischemic brain injury, mitochondrial functions are compromised and the lack of electron acceptors leads to free radical leakage from the mitochondria into the cytoplasm, causing lipid peroxidation of polyunsaturated fatty acid-rich neuronal membranes (1,2).Danshen is derived from the dried root or rhizome of Salviae Miltiorrhizae Bge. In recent decades, Danshen has been commonly used in China for the treatment of angina pectoris and cerebrovascular disorders such as ischemic stroke (3). Tanshinone IIA, a derivative of phenanthrenequinone, is one of the key components of Danshen (Fig. 1). It has antioxidant properties and has been demonstrated to protect against lipid peroxidation in in vitro and in vivo studies (4,5). Tanshinone IIA can prevent the neuroblastoma cell line PC12 from apoptosis induced by serum-free culture conditions (6). It has the potential to penetrate the blood-brain barrier and acts as an inhibitor...

Endothelial nitric oxide synthase is a molecular vascular target for the Chinese herb Danshen in hypertension

“…Tanshinone II A has antioxidant properties and protects against lipid peroxidation in vitro and in vivo, making it a potential antidote for free radical-based disorders (27,39,42). In addition, tanshinone II A has neuroprotective effects in cerebral ischemia and attenuates angiotensin II-induced hypertrophy (21,35,40). Tanshinone II A may also have a role as a therapeutic drug in the treatment of bone diseases such as osteoporosis (20).…”

Synergistic Increase of BDNF Release from Rat Primary Cortical Neuron by Combination of Several Medicinal Plant-Derived Compounds

“…These compounds have been reported to have either neuroprotective or anti-oxidative effects (Kim and Kim, 2000;Piao et al, 2004;Xia et al, 2005;Jung et al, 2009;Mu et al, 2009;Yu et al, 2009). However, not all natural compounds having neuroprotective or anti-oxidative effects showed increased BDNF release.…”

Tanshinone IIA ameliorates lead (Pb)-induced cognitive deficits and oxidative stress in a rat pup model

“…Antioxidants counteract the detrimental effects of oxidative stress in biological systems. TSA can increase neural progenitor cell line viability and protect cells against mitochondrial damage owing to its anti-oxidative activities (10). In particular, TSA alleviates H 2 O 2 -induced hippocampal long-term potentiation impairment against the neurotoxic effects of oxidative damage (11).…”