A novel indication of platonin, a therapeutic immunomodulating medicine, on neuroprotection against ischemic stroke in mice.
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 μg/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 μM) 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 μg/kg)-treated mice. Platonin(2-10 μM) was potent in diminishing collagen- and Fenton reaction-induced∙OH formation. Platonin(5-10 μM) also suppressed the expression of nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-1β, and JNK phosphorylation in lipopolysaccharide-stimulated macrophages. MCAO-induced expression of 3-nitrotyrosine and Iba1 was apparently attenuated in platonin(200 μg/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.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Joen-Rong
JR
Sheu
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Cardiology, Chi-Mei Medical Center, Tainan City, Taiwan.|Department of Pharmacy, Chia Nan University of Pharmacy &Science, Tainan City, Taiwan.
Zhih-Cherng
ZC
Chen
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Thanasekaran
T
Jayakumar
Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Duen-Suey
DS
Chou
Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Ting-Lin
TL
Yen
Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Hsing-Ni
HN
Lee
Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Szu-Han
SH
Pan
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chih-Hsuan
CH
Hsia
Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chih-Hao
CH
Yang
Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Cheng-Ying
CY
Hsieh
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D003094:Collagen; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D000067996:RAW 264.7 Cells; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D005609:Free Radicals; D007155:Immunologic Factors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D013844:Thiazoles; C032149:platonin; D003094:Collagen; D048031:JNK Mitogen-Activated Protein Kinases