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The study explores the protective role of the peripheral serum of limb remote ischemic postconditioning (LRIP) in reducing the reactive oxygen species (ROS) levels and neutrophil activation, which are responsible for the deleterious reperfusion injury. LRIP was induced in Sprague–Dawley rats by three cycles of 5 min occlusion /5 min reperfusion on the left hind limb. The blood samples were collected before LRIP or 0 and 1 h after LRIP (named SerumSham, SerumLRIP0, SerumLRIP1, respectively). The effects of LRIP serum on ROS level and neutrophils activation were determined. The expression of MyD88-TRAF6-MAPKs and PI3K/AKT pathways in neutrophils were examined. When compared with SerumSham, SerumLRIP0 and SerumLRIP1 significantly reduced the ROS released from neutrophils activated by fMLP. Meanwhile, the mRNA expression levels of NADPH oxidase subunit p22phox and multiple ROS-producing related key proteins, such as NADPH oxidase subunit p47phox ser 304, ser 345. MyD88, p-ERK, p-JNK and p-P38 expression of neutrophils were downregulated by SerumLRIP0 and SerumLRIP1. SerumLRIP1 also downregulated p47phox mRNA expression and tumor necrosis factor receptor-associated factor 6 (TRAF6) protein expression. LRIP serum protects against ROS level and neutrophils activation involving the MyD88-TRAF6-MAPKs. This finding provides new insight into the understanding of LRIP mechanisms. [ABSTRACT FROM AUTHOR]

ContextShengmai injection (SMI) is a patented Chinese medicine originated from the ancient Chinese herbal compound Shengmai san, which is used extensively for the treatment of cardiovascular and cerebrovascular disease in the clinic. ObjectiveTo determine the neuroprotective effect of SMI, we investigated the effect of SMI on cerebral ischemia/reperfusion (I/R) injury in mice as well as the mechanisms underlying this effect. Materials and methodsRight middle cerebral artery was occluded by inserting a thread through internal carotid artery for 1 h, and then reperfused for 24 h in mice. The neuroprotective effects were determined using transmission electron microscopic examination, the evaluation of infarct volume, neurological deficits and water brain content. Related mechanisms were evaluated by immunofluorescence staining and western blotting. SMI was injected intraperitoneally after 1 h of ischemia at doses of 1.42, 2.84 and 5.68 g/kg. The control group received saline as the SMI vehicle. ResultsResults showed that SMI (1.42, 2.84 and 5.68 g/kg) could significantly reduce the infarct volume, SMI (5.68 g/kg) could also significantly improve the neurological deficits, decreased brain water content, as well as the neuronal morphological changes. SMI (5.68g/kg) could significantly inhibit the expression of autophagy-related proteins: Beclin1 and LC3. It also reduced the increase in LC3-positive cells. SMI (5.68 g/kg) remarkably inhibited the phosphorylation of adenosine monophosphate activated protein kinase (AMPK), and down-regulated the phosphorylation of mammalian target of rapamycin (mTOR) and Jun N-terminal kinase (JNK) after 24 h of reperfusion. Discussion and conclusionThe results indicate that SMI provides remarkable protection against cerebral ischemia/reperfusion injury, which may be partly due to the inhibition of autophagy and related signalling pathways. [ABSTRACT FROM PUBLISHER]

Progress intreating cerebral ischemia with an extract of Ginkgo biloba L. (Ginkgoaceae), commonly known as EGb 761, has been made in the past. However, neuroprotective interaction of the two main active fractions, flavonoids and terpenoids, still remains vague. In the current study, we investigated the neuroprotective effects of Ginkgo flavonoids, terpenoids, and their combinations in ratios of 16:1, 4:1, and 1:1 on brain damage in mice injured by ischemia-reperfusion. Pretreatment with total flavonoids, total terpenoids, their three combinations, or EGb 761 for 7 days each at two doses of 15 and 30 mg/kg might elevate latency and decrease error numbers to different extents in the passive avoidance test, but only the action of the 4:1 combination besides EGb 761 was significant. In addition, the gasping time in decapitated mice was prolonged markedly by the 4:1 and 1:1 combinations at 15 and 30 mg/kg and by total flavonoids other than total terpenoids at 30 mg/kg. Neurochemical assays further showed that flavonoids significantly decreased malondialdehyde, superoxide anion contents, and xanthine oxidase activity, meanwhile terpenoids markedly suppressed myeloperoxidase activity besides its slight antioxidant effect. These findings suggest that flavonoids and terpenoids contribute synergistically to the neuroprotection of EGb 761 mainly via antioxidant activity and anti-inflammatory activity, respectively, and the 4:1 combination, namely the natural ratio in EGb 761, shows the strongest effects among those of the three combinations. [ABSTRACT FROM AUTHOR]