Shibata_2018_Eur.J.Pharmacol_818_221

We reported previously that Stachybotrys microspora triprenyl phenol-7 (SMTP-7) showed potential thrombolytic, anti-inflammatory and anti-oxidant effects that account for its excellent pharmacological activity such as having a wider therapeutic time window than tissue plasminogen activator (t-PA) and a significant protection against hemorrhage. The aim of the present study was to evaluate and compare the effect of a new series of SMTPs in the acetic acid-induced embolic cerebral infarct mouse model. Thrombotic occlusion was produced in mice by inducing the transfer of acetic acid-induced thrombi from the right common carotid artery into the brain. SMTPs were evaluated by their effect on reducing infarct area, neurological score and edema. Furthermore, plasmin formation, anti-inflammatory and anti-oxidant activities were assessed by fibrin zymography, measuring pro-inflammatory gene expression, and thiobarbituric acid reactive substances (TBARS) assay, respectively. Treatment with either SMTP-22 or SMTP-43 (10mg/kg), which have similar plasmin formation, anti-inflammatory and anti-oxidant activities to SMTP-7, resulted in reduced infarct area, neurological score and edema. Coexistence of all these three activities appears to be important for the treatment of embolic infarction because SMTP-6, SMTP-25, and SMTP-44D (10mg/kg), which are each missing at least one of the three functions, were not as effective. Therefore, these results indicate that SMTP-22 and SMTP-43 have potential as medicinal compounds for the treatment of embolic cerebral infarction.