Pretreatment with Shuanghe‐Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam

Abstract

Aim Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. Methods Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4) was performed following ischemic injury. Results Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB) breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg), while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1) expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

Weisheng-Tang Ameliorates Acute Ischemic Brain Damage in Mice by Maintaining Blood-Brain Barrier Integrity

“…Focal cerebral ischemia was induced by photothrombosis of the cortical microvessels, as previously described [7]. Briefly, mice were anesthetized with 2% isoflurane in 20% O 2 and 80% N 2 O; subsequently, they received an intraperitoneal (i.p.)…”

“…Neurological deficits were evaluated 24 h after ischemic injury using the following scoring system: 1 = turning in the direction of the ipsilateral (nondamaged) side when held by the tail, 2 = turning in the direction of the contralateral (damaged) side and difficulty bearing weight, 3 = unable to bear weight on the contralateral side, and 4 = no spontaneous movement [7].…”

“…Each mouse was suspended on a metal wire and forced to hang using both forepaws. Wire grip was scored as follows: 1 = not holding onto the wire; 2 = holding onto the wire using both forepaws and hind paws but not the tail; 3 = holding onto the wire using both forepaws and hind paws as well as the tail, without movement; 4 = moving on the wire using both forepaws, both hind paws, and tail; and 5 = moving well on the wire [7].…”

“…Indeed, researchers have begun to consult traditional medicine literature in the search for novel therapeutic strategies [6]. In our previous study, we investigated the effectiveness of 29 medical herbs in the treatment of stroke symptoms based on Dongeuibogam text-mining analysis and a mouse model of cerebral ischemia and selected the formula “Shuanghe-tang” as the candidate herbal medicinal formulas for ischemic stroke [7]. Pretreatment with Shuanghe-tang significantly reduced infarct volume and edema and improved neurological and motor functions [7].…”

“…In our previous study, we investigated the effectiveness of 29 medical herbs in the treatment of stroke symptoms based on Dongeuibogam text-mining analysis and a mouse model of cerebral ischemia and selected the formula “Shuanghe-tang” as the candidate herbal medicinal formulas for ischemic stroke [7]. Pretreatment with Shuanghe-tang significantly reduced infarct volume and edema and improved neurological and motor functions [7]. Subsequently, we searched the traditional Korean medical literature once again to select new herbal medicinal formulas for the treatment of ischemic stroke using the revised criteria obtained from our previous research.…”