Mimopezil

SPAK inhibitor ZT-1a was previously shown to be neuroprotective in murine ischemic stroke models. In this study, we further examined the efficacy of four ZT-1a derivatives (ZT-1c, -1d, -1g and -1h) on reducing stroke-induced sensorimotor function impairment and brain lesions. Vehicle control (Veh) or ZT-1 derivatives were administered via osmotic pump to adult C57BL/6J mice during 3-21 h post-stroke. Neurological behavior of these mice was assessed at days 1, 3, 5, and 7 post-stroke and MRI T2WI and DTI analysis was subsequently conducted in ex vivo brains. Veh-treated stroke mice displayed sensorimotor function deficits compared to Sham mice. In contrast, mice receiving ZT-1a derivatives displayed significantly lower neurological deficits at days 3-7 post-stroke (p < 0.05), with ZT-1a, ZT-1c and ZT-1d showing greater impact than ZT-1h and ZT-1g. ZT-1a treatment was the most effective in reducing brain lesion volume on T2WI and in preserving NeuN + neurons (p < 0.01), followed by ZT-1d > -1c > -1g > -1h. The Veh-treated stroke mice displayed white matter tissue injury, reflected by reduced fractional anisotropy (FA) or axial diffusivity (AD) values in external capsule, internal capsule and hippocampus. In contrast, only ZT-1a-as well as ZT-1c-treated stroke mice exhibited significantly higher FA and AD values. These findings demonstrate that post-stroke administration of SPAK inhibitor ZT-1a and its derivatives (ZT-1c and ZT-1d) is effective in protecting gray and white matter tissues in ischemic brains, showing a potential for ischemic stroke therapy development.

Previous work showed that peptides from duck eggs incubated for 15 D presented high total antioxidant activities. Here, this work explore the antioxidant activities of different segments, ZT1 (≤3 KD), ZT2 (≤10 KD), and ZT3 (≤30 KD), derived from duck embryo peptides and their protective effects against H2O2-induced oxidative damage in HepG2 cells. Peptides present no cytotoxicity to HepG2 cells. Moreover, ZT1 exhibits a higher ability to scavenge several radicals as well as stronger inhibition of H2O2-induced oxidative stress than ZT2 and ZT3. The activities of catalase and glutathione peroxidase as well as total superoxide dismutase increase in a concentration-dependent manner. Peptides are isolated from ZT1 and then subjected to LC-MS/MS to identify their sequences, followed by functional annotation, bioinformatics prediction, and hot-spot motif recognition. As a result, 413 potential functional peptides are identified, with some compounds exhibiting more than 1 function. This work will help for exploring bioactive substances in duck embryo eggs and enhance the utilization value of duck or other poultry eggs.