The Traditional Herbal Medicine, Dangkwisoo‐San, Prevents Cerebral Ischemic Injury through Nitric Oxide‐Dependent Mechanisms

Abstract

Dangkwisoo-San (DS) is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO) production in human brain microvascular endothelial cells (HBMECs). DS (10–300 μg/mL) produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS) inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF), although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS) inhibitor, N5-(1-iminoethyl)-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation.

Effects of Dangkwisoo-san, a traditional herbal medicine for treating pain and blood stagnation, on the pacemaker activities of cultured interstitial cells of Cajal

“…Generally, DS has been traditionally used in Korea for the treatment of pain and blood stagnation caused by physical trauma (4). In the present study, however, it was found that DS modulated GI motility using ICCs.…”

“…The combination of multiple drugs is considered to maximize therapeutic efficacy by facilitating synergistic actions and preventing potential adverse effects (2). Dangkwisoo-san (DS) is a herbal formula, which has been traditionally used for the treatment of pain and blood stagnation caused by physical trauma in Korea (4). DS contains constituents of nine species of herbal plants, including Angelicae gigantis Radix, Paeoniae Radix, Linderae Radix, Sappan Lignum, Cyperi Rhizoma, Carthami Flos, Persicae Semen, Cinnamomi Cortex and Glycyrrhizae Radix et Rhizoma, which have various pharmacological effects on the body (5,6).…”

Method parameters’ impact on mortality and variability in mouse stroke experiments: a meta-analysis

“…The Infarct size coefficient of variation (in the total 500 control groups9101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108109110…”

Anti-Inflammatory and Anti-Oxidative Effects of Danggwisusan on Macrophages

“…Previous studies have reported headache relief [5], external injury amelioration [6], fracture healing [7], subcutaneous hematoma amelioration [8], antithrombotic [9], cerebral ischemic injury amelioration [10], allergic purpura amelioration [11], and pain control [12] effects of Danggwisusan.…”