Abstract
Stroke is one of the major causes of death and long-term disability worldwide; the associated breakdown of the blood-brain barrier (BBB) aggravates ischemic brain damage. Accordingly, many medicinal herbs and formulas have been used to treat stroke-related symptoms. In this study, we selected two Korean herbal medicine formulas, Weisheng-tang and Tongxuewan, through Dongeuibogam text-mining analysis, and evaluated their protective effect on BBB disruption and brain damage in stroke. Ischemic brain damage was induced in mice by photothrombotic cortical ischemia. The infarct volume, brain edema, neurological deficits, and motor function 24 h after ischemic injury were analyzed. We investigated BBB breakdown by measuring Evans blue extravasation in addition to endothelial cells, tight junction proteins, protease-activated receptor-1 (PAR-1), and matrix metalloproteinase-9 (MMP-9) using immunofluorescence staining and confocal microscopy. Pretreatment with Weisheng-tang significantly reduced infarct volume and edema and improved neurological and motor functions; however, Tongxuewan did not. In addition, Weisheng-tang decreased brain infarction and edema and recovered neurological and motor deficit in a dose-dependent manner (30, 100, and 300 mg/kg). Weisheng-tang pretreatment resulted in significantly less BBB damage and higher brain microvasculature after focal cerebral ischemia. Tight junction proteins, such as zonula occludens-1 (ZO-1) and claudin-5, were preserved in Weisheng-tang-pretreated mice. Moreover, the ischemic brain in these mice showed suppressed PAR-1 and MMP-9 expression. In conclusion, our findings show that Weisheng-tang, which was selected through literature analysis but has not previously been used as a stroke remedy, exerts protective effects against ischemic brain damage and suggest its possible application for potential stroke patients, especially in the elderly.
Highlights
Stroke is one of the leading causes of serious and long-term disability worldwide, stroke mortality has been declining [1]
We examined the protective effect of Tongxuewan or Weisheng-tang on the parameters of ischemic brain damage and blood-brain barrier (BBB) disruption, such as the infarct volume, brain edema, neurological deficits, motor function, and Evans blue extravasation using the focal cerebral ischemia mouse model
In line with the results of previous studies, our results showed a high level of protease-activated receptor-1 (PAR-1) expression in the peri-infarct region after focal cerebral ischemia, indicating that Protease-activated receptors (PARs)-1 induction contributes to the expansion of brain damage
Summary
Stroke is one of the leading causes of serious and long-term disability worldwide, stroke mortality has been declining [1]. Treatment of stroke has been traditionally focused on reducing ischemic cell death; clinical trials have shown that none of the tested neuroprotective drugs achieve clinical benefit for the treatment of acute stroke [2]. The failure of clinical trials provide evidence that new therapeutic strategies for acute stroke need to be explored; one such strategy might involve the preservation of the integrity of the blood-brain barrier (BBB) [2]. Tongxuewan Cnidium officinale Makino Angelica gigas Nakai Saposhnikovia divaricata Schiskin Schizonepeta tenuifolia Briquet Rehmannia glutinosa Libosch.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
