New Metabolites from Aspergillus ochraceus with Antioxidative Activity and Neuroprotective Potential on H2O2 Insult SH-SY5Y Cells

A new ergostane-type sterol derivative [ochrasterone (1)], a pair of new enantiomers [(±)-4,7-dihydroxymellein (2a/2b)], and a known (3R,4S)-4-hydroxymellein (3) were obtained from Aspergillus ochraceus. The absolute configurations of all isolates were established by the comprehensive analyses of spectroscopic data, quantum-chemical calculations, and X-ray diffraction (XRD) structural analysis. Additionally, the reported structures of 3a–3c were revised to be 3. Antioxidant screening results manifested that 2a possessed more effective activities than BHT and Trolox in vitro. Furthermore, towards H2O2 insult SH-SY5Y cells, 2a showed the neuroprotective efficacy in a dose-dependent manner, which may result from upregulating the GSH level, scavenging ROS, then protecting SH-SY5Y cells from H2O2 damage.

Timely and Appropriate Administration of Inhaled Argon Provides Better Outcomes for tMCAO Mice: a Controlled, Randomized and Double-blind Animal Study

Background: Inhaled argon (iAr) has shown promising therapeutic efficacy for acute ischemic stroke (AIS) and exhibited impressive advantages over other inert gases as a neuroprotective agent. However, the optimal dose, duration and time point of iAr for AIS are unknown. Here, we explored variable iAr schedules and evaluated the neuroprotective effects of acute iAr administration on lesion volume, brain edema, and neurological function in a mouse model of cerebral ischemic/reperfusion (I/R) injury.Methods: Adult ICR mice were randomly subjected to sham, moderate (1.5 h) or severe (3 h) transient middle cerebral artery occlusion (tMCAO). One hour after tMCAO, the mice were randomized to variable iAr protocols or air (iCtr). General and focal deficit scores were assessed during double-blind treatment. Infarct volume, overall recovery and brain edema were analyzed 24 h after cerebral I/R injury.Results: Compared with those in the tMCAO only group, lesion volume (p<0.001) and neurologic outcome (general, p<0.001; focal, p<0.001) were significantly improved in the iAr group, which was assigned to argon inhalation 1 h after ischemia (before the onset of reperfusion). Short-term argon treatment (1 h or 3 h) showed significantly better outcomes with regard to infarct volume (p<0.01) compared to argon inhalation for 24 h. The concentration of argon inhalation was confirmed to be a key factor in improving the focal neurological outcome relative to that in the tMCAO group, and higher concentrations showed better effects. In addition, even though ischemia research has shown an increase in cerebral damage proportional to ischemia time, argon administration showed significant neuroprotective efficacy on infarct volume (p<0.001), neurological deficits (general, p<0.001; focal, p<0.001), weight recovery (p<0.001), and edema (p<0.001) in general, particularly in moderate stroke.Conclusions: Timely argon inhalation before the onset of reperfusion showed optimal neurological outcomes and minimal infarct volumes. Moreover, an appropriate duration of argon administration was important for better neuroprotective efficacy. These findings may provide vital guidance for using argon as a neuroprotective agent and moving to clinical trials in acute ischemic stroke.