A novel indication of platonin, a therapeutic immunomodulating medicine, on neuroprotection against ischemic stroke in mice

作者:Sheu Joen Rong; Chen Zhih Cherng; Jayakumar Thanasekaran; Chou Duen Suey; Yen Ting Lin; Lee Hsing Ni; Pan Szu Han; Hsia Chih Hsuan; Yang Chih Hao*; Hsieh Cheng Ying*
来源:Scientific Reports, 2017, 7(1): 42277.
DOI:10.1038/srep42277

摘要

Thrombosis and stroke are major causes of disability and death worldwide. However, the regular antithrombotic drugs may have unsatisfactory results and side effects. Platonin, a cyanine photosensitizing dye, has been used to treat trauma, ulcers and some acute inflammation. Here, we explored the neuroprotective effects of platonin against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in mice. Platonin(200 mu g/kg) substantially reduced cerebral infarct volume, brain edema, neuronal cell death and neurological deficit scores, and improved the MCAO-reduced locomotor activity and rotarod performance. Platonin(5-10 mu M) potently inhibited platelet aggregation and c-Jun NH2-terminal kinase (JNK) phosphorylation in collagen-activated platelets. The antiaggregation effect did not affect bleeding time but increased occlusion time in platonin(100 and 200 mu g/kg)-treated mice. Platonin(2-10 mu M) was potent in diminishing collagen-and Fenton reaction-induced (OH)-O-center dot formation. Platonin(5-10 mu M) also suppressed the expression of nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-1 beta, and JNK phosphorylation in lipopolysaccharide-stimulated macrophages. MCAO-induced expression of 3-nitrotyrosine and Iba1 was apparently attenuated in platonin(200 mu g/kg)-treated mice. In conclusion, platonin exhibited remarkable neuroprotective properties against MCAO-induced ischemia in a mouse model through its antiaggregation, antiinflammatory and antiradical properties. The observed therapeutic efficacy of platonin may consider being a novel medcine against ischemic stroke.