Ginsenoside Represses Symptomatic Intracerebral Hemorrhage after Recombinant Tissue Plasminogen Activator Therapy by Promoting Transforming Growth Factor-β1

Abstract

Currently, the most effective treatment for brain ischemic stroke is recombinant tissue plasminogen activator (rt-PA); however, increased incidence of symptomatic intracerebral hemorrhage severely reduced its favorable treatment outcome. We aimed to investigate the effect of ginsenoside (Gs) on symptomatic intracerebral hemorrhage after rt-PA treatment. Stroke patients were randomly divided into 2 treatment groups, one receiving rt-PA + placebo (Pc) and the other rt-PA + Gs. Twenty-four hours after the treatment, outcomes were assessed with transcranial Doppler (TCD) ultrasonography and National Institutes of Health Stroke Scale (NIHSS), and plasma levels of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase (MMP)-2, and MMP-9 were also measured. After initial cotreatment, the patients were continuously administered with either Pc or Gs, and the treatment outcomes at 7 days were assessed with TCD, NIHSS, modified Rankin scale (MRS), and Glasgow outcome scale (GOS). Cotreatment of rt-PA with Gs significantly improved outcomes in patients compared to the Pc group, as indicated by improved TCD and NIHSS scores and reduced incidence of symptomatic intracerebral hemorrhage, which could be attributed to a Gs-induced increase in TGF-β1 and a decrease in both MMP-2 and MMP-9 serum levels. Seven days of Gs treatment also significantly improved outcomes in patients compared to the Pc group, assessed by TCD, NIHSS, MRS, and GOS. Our study supports the clinical use of Gs as a potential supplement with rt-PA treatment, which reduces symptomatic intracerebral hemorrhage, therefore improving the treatment outcome of stroke patients.