No abstract

Our previous study demonstrates that SYB produces a neuroprotective effect in vivo. In the present study, we investigated the protective effect of safflor yellow B (SYB) on the acute oxidative injury induced by H(2)O(2) and mechanisms in PC12 cells. H(2)O(2) was used to mimic in vitro model of the oxidative injury and to induce apoptosis in PC12 cells. The cells were pretreated with the different concentrations of SYB. The cell viability, lactate dehydrogenase (LDH) release, malondialdehyde (MDA), and superoxide anion levels, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured. Caspase 3 activity, Bcl-2 and Bax expressions were also observed. The results showed that exposure of the cells to H(2)O(2) significantly decreased the cell viability, SOD and GSH-Px activities and Bcl-2 expression, and increased LDH release, superoxide anion and MDA generations, caspase 3 activity and Bax expressions. Pretreatment of the cells with SYB was able to remarkably antagonize the H(2)O(2)-induced changes in dose-dependent way. These suggest that SYB is able to protect PC12 cells from H(2)O(2)-induced injury and apoptosis via antioxidant and anti-apoptotic mechanisms.

Protopine, an isoquinoline alkaloidis, is known to produce many effects such as vasodilation, down-regulation of glutamate levels in brain and decrease of intracellular calcium. However, so far there is no report on the effect of protopine in cerebral ischaemia. In this study, the effect of protopine on the focal cerebral ischaemia was investigated in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-treated group and three doses of protopine-treated groups (0.98, 1.96 and 3.92 mg/kg). Protopine was intraperitoneally administered to rats once daily for 3 days prior to the ischaemia and 0.9% normal saline to rats in the vehicle-treated group in the same pattern. Rats in the sham-operated group were given 0.9% normal saline without the ischaemia. The focal cerebral ischaemia was induced by the middle cerebral artery occlusion for 24 hr via the intraluminal filament technique. The results showed that pretreatment with protopine reduced the cerebral infarction ratio and serum lactate dehydrogenase activity, and improved the ischaemia-induced neurological deficit score and histological changes of brain in a dose-dependent manner. The further studies demonstrated that protopine increased superoxide dismutase activity in serum, and decreased total calcium and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL)-positive cells in the ischaemic brain tissue in the middle cerebral artery occlusion rats. The results indicate that protopine is able to produce an effective protection on the injury caused by the focal cerebral ischaemia in rats possibly through the multiple effects of calcium antagonism, antioxidation and depression of cell apoptosis.Cerebral ischaemia or stroke is one of the leading causes of death and the single most common cause of severe disability in many countries. Human cerebral ischaemia often results from a transient or permanent occlusion of the middle cerebral artery. Brain tissue has a relatively high consumption of oxygen and glucose, and almost exclusively depends on oxidative phosphorylation for energy production. Following focal cerebral ischaemia, energy failure from critical blood perfusion deficit leads to disruption of ion homeostasis, generation of free radicals, initiation of apoptosis, inflammation and release of excitatory amino acids, most notably glutamate [1,2]. These result in a progressive accumulation of intracellular sodium and calcium ions, which can precipitate in necrosis and/or apoptosis of vulnerable neurones [1,3,4].Protopine is an isoquinoline alkaloid with multiple pharmacological actions. Protopine reduces intracellular calcium [5], inhibits arachidonic acid and platelet-activating factorinduced platelet aggregation by decreasing the cytosolic calcium in the rabbit [6] and suppresses thromboxane A 2 synthesis and inflammatory process via the cyclooxygenase pathway [7]. Protopine also down-regulates glutamate level in rat brain through activation of glutamate dehydrogenase [8]. In addition, it h...