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Efficacy of SMTP-7, a small-molecule anti-inflammatory thrombolytic, in embolic stroke in monkeys.

ABSTRACT: SMTP-7 (Stachybotrys microspora triprenyl phenol-7) is a small molecule that promotes thrombolysis and suppresses inflammation possibly through plasminogen modulation and soluble epoxide hydrolase (sEH) inhibition, respectively. Here, we demonstrate an efficacy of SMTP-7 in a severe embolic stroke model in monkeys. The middle cerebral artery was embolized by an autologous blood clot. Saline, SMTP-7, or tissue-type plasminogen activator (t-PA) (n = 5 in each group) was given after 3 hours, and neurologic deficit scoring and infarct characterization were performed after 24 hours. Hemorrhagic infarct-accompanied premature death was observed for two animals in t-PA group. SMTP-7 treatment significantly reduced the sizes of infarct by 65%, edema by 37%, and clot by 55% compared to saline treatment. Plasma levels of the products of plasminogen activation (plasmin-?2-antiplasmin complex) and sEH reaction (dihydroxyeicosatrienoic acid) in SMTP-7 group were 794% (P < 0.05) and 60% (P = 0.085) compared to saline group, respectively. No significant changes in the plasma levels of MMP-9, CRP, MCP-1, and S100B were found. There was an inverse correlation between plasmin-?2-antiplasmin complex level and infarct volume (r = 0.93, P < 0.05), suggesting a role of thrombolysis in the SMTP-7 action to limit infarct development. In conclusion, SMTP-7 is effective in treating severe embolic stroke in monkeys under conditions where t-PA treatment tends to cause hemorrhagic infarct-associated premature death.

SUBMITTER: Suzuki E

PROVIDER: S-EPMC6282002 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Efficacy of SMTP-7, a small-molecule anti-inflammatory thrombolytic, in embolic stroke in monkeys.

Suzuki Eriko E Nishimura Naoko N Yoshikawa Tetsuya T Kunikiyo Yudai Y Hasegawa Keiko K Hasumi Keiji K

Pharmacology research & perspectives 20181205 6

SMTP-7 (<i>Stachybotrys microspora</i> triprenyl phenol-7) is a small molecule that promotes thrombolysis and suppresses inflammation possibly through plasminogen modulation and soluble epoxide hydrolase (sEH) inhibition, respectively. Here, we demonstrate an efficacy of SMTP-7 in a severe embolic stroke model in monkeys. The middle cerebral artery was embolized by an autologous blood clot. Saline, SMTP-7, or tissue-type plasminogen activator (t-PA) (n = 5 in each group) was given after 3 hours, ...[more]

PMID: 30546909

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Dataset Information

Efficacy of SMTP-7, a small-molecule anti-inflammatory thrombolytic, in embolic stroke in monkeys.

Publications

Efficacy of SMTP-7, a small-molecule anti-inflammatory thrombolytic, in embolic stroke in monkeys.

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