Realgar and cinnabar are essential components contributing to neuroprotection of Angong Niuhuang Wan with no hepatorenal toxicity in transient ischemic brain injury

被引：17

作者：

Tsoi, Bun ^{[1
]}

Wang, Songlin ^{[1
]}

Gao, Chong ^{[1
]}

Luo, Yunhao ^{[2
]}

Li, Wenting ^{[1
]}

Yang, Dan ^{[3
]}

Yang, Depo ^{[4
]}

Shen, Jiangang ^{[1
]}

机构：

[1] Univ Hong Kong, Sch Chinese Med, Li Ka Shing Fac Med, Hong Kong, Peoples R China

[2] Univ Hong Kong, Sch Biomed Sci, Li Ka Shing Fac Med, Hong Kong, Peoples R China

[3] Univ Hong Kong, Fac Sci, Dept Chem, Hong Kong, Peoples R China

[4] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou, Guangdong, Peoples R China

来源：

TOXICOLOGY AND APPLIED PHARMACOLOGY | 2019年 / 377卷

基金：

中国国家自然科学基金;

关键词：

Heavy metal toxicity; Realgar; Cinnabar; Angong Niuhuang Wan; Cerebral ischemia-reperfusion injury; Safety; NIU-HUANG WAN; HEMORRHAGIC TRANSFORMATION; TRADITIONAL MEDICINES; MEDIATED DISRUPTION; MERCURY TOXICITY; ARSENIC TOXICITY; REPERFUSION; MANAGEMENT; APOPTOSIS; THERAPY;

D O I：

10.1016/j.taap.2019.114613

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Realgar and cinnabar are commonly used mineral medicine containing arsenic and mercury in Traditional Chinese Medicine (TCM). Angong Niuhuang Wan (AGNHW) is a representative realgar- and cinnabar-containing TCM formula for treating acute ischemic stroke, but its toxicology and neuropharmacological effects are not well addressed. In this study, we compared the neuropharmacological effects of AGNHW and modified AGNHW in an experimental ischemic stroke rat model. Male SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus 22 h of reperfusion. Although oral administration of AGNHW for 7 days in the rats increased arsenic level in the blood and liver tissue, there were no significant changes in the arsenic level in kidney, mercury level in the blood, liver and kidney as well as hepatic and renal functions in MCAO rats. AGNHW revealed neuroprotective properties by reducing infarction volume, preserving blood-brain barrier integrity and improving neurological functions against cerebral ischemia-reperfusion injury. Interestingly, removing realgar and/or cinnabar from AGNHW abolished the neuroprotective effects. Meanwhile, AGNHW could scavenge peroxynitrite, down-regulate the expression of p47(phox), 3-NT and MMP-9 and up-regulate the expression of ZO-1 and claudin-5 in the ischemic brains, which were abolished by removing realgar and/or cinnabar from AGNHW. Notably, realgar or cinnabar had no neuroprotection when used alone. Taken together, oral administration of AGNHW for one week should be safe for treating ischemic stroke with neuroprotective effects. Realgar and cinnabar are necessary elements with synergetic actions with other herbal materials for the neuroprotective effects of AGNHW against cerebral ischemia-reperfusion injury.

引用

页数：12