Protection of Tong-Qiao-Huo-Xue Decoction against Cerebral Ischemic Injury through Reduction Blood–Brain Barrier Permeability

Abstract

Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classical prescription in traditional Chinese medicine treating blood stagnation in the head and facial channels, especially cerebral ischemia. We investigate the effect of TQHXD on the expressions of related proteins of the blood-brain barrier (BBB) and analysis of constituents in the cerebrospinal fluid (CSF) on cerebral ischemic model rats. Here, we demonstrate that TQHXD protected the hippocampus neurons, reduced the opening of tight junction (TJ) and decreased the permeability of BBB by up-regulating ZO-1, occludin, claudin-5 expressions, down-regulating aquaporin-4 (AQP-4) and matrix metalloproteinase-9 (MMP-9) expressions. Meanwhile, we detected Muscone, ligustilide and hydroxysafflor yellow A in CSF on cerebral ischemic model rats. These compounds could be identified as the main active ingredients of TQHXD on protecting the damaged BBB. These results suggest that TQHXD could act as a potential neuroprotective agent against BBB damage for cerebral ischemia.Key words Tong-Qiao-Huo-Xue Decoction; cerebral ischemia injury; blood-brain barrier; tight junction; cerebrospinal fluid Ischemia brain damage is one of the most challenging central nervous system (CNS) diseases which threaten human life and health due to its high rates of disability and mortality.1,2) The blood-brain barrier (BBB) injury is an important performance in ischemia brain damage.3) BBB is a highly specialized structure in CNS that comprises arachnoid membranes, cerebral capillary endothelial cells, and the choroid plexus epithelium. 4,5) These layered cell structures construct the so-called tight junction (TJ) and the TJ-associated protein of Claudin-5, Occludin and ZO-1, which contribute to the integrity of the BBB, and the changes of its composition and the expression of relative ingredients are closely associated with BBB permeability.6-8) These proteins are the major structural protein of TJ, their expressions levels are relevant to the degree of cerebral microvascular permeability and cerebral edema.In recent years, experimental reports and clinical applications of traditional Chinese medicine (TCM) against cerebral ischemia injury had shown superiority because of its effects of multiple targeting and multi-directional regulations.9) TongQiao-Huo-Xue Decoction (TQHXD) is a classical prescription in traditional Chinese medicines, prescribed by Qingren Wang, a distinguished doctor of the Qing Dynasty, comprising seven Chinese herbs (Table 1). TQHXD promotes blood circulation by removing blood stasis, and induces resuscitation by dredging the channels. It has remarkable efficacy on the treatment of stagnation of blood in the head and facial channels, 10) especially cerebral ischemia. Our previous experiments in vivo and vitro showed that TQHXD had beneficial effects in cerebral ischemia.11-16) However, we just investigated the effect of TQHXD on cerebral ischemia from the perspective of pharmacodynamics. Moreover, the model of animal used in the experiment was a cerebral ischemic model established ...

Protective Effect of Tong-Qiao-Huo-Xue Decoction on Inflammatory Injury Caused by Intestinal Microbial Disorders in Stroke Rats

“…Our research group had established HPLC fingerprints of TQHXD for the quality control, and analyzed the chemical constituents in rat cerebrospinal fluid by GC and HPLC after TQHXD administration 26,27) . Previous studies by our team showed that TQHXD has a protective effect on the injury to cerebral ischemia reperfusion rats and the injury to PC12 cells 27,28) . At the same time, inflammatory cell infiltration was found in the ischemic hemisphere.…”

“…Weighed 10 times the weight of the TQHXD original medicinal material, and soaked in 10 times 75% ethanol for 2 h, and refluxed for 2 h, then filtered and added 8 times of 75% ethanol with refluxing for 1.5 h, and combined the filtrate. Then 1.5 g artificial musk was mixed into the extract, and the solution was adjusted to a concentration of 2 g/mL 27) .…”

“…When the blood-brain barrier is damaged, its permeability increases, and harmful substances in the blood easily enter brain tissue, which aggravates brain cell damage 54) . In the previous study 27) , the research team had…”

Gypenosides protect against cardiac ischemia-reperfusion injury by inhibiting mitochondria-dependent apoptosis

“…Recent research suggested that components used in traditional Chinese medicine are protective in I/R injury [7,8]. One such medicinal herb, Gynostemma pentaphyllum, is popularly used to treat chronic inflammation, cancer, cardiovascular disease, and hepatitis.…”

The Establishment of the Method of Cell Biochromatograpy and Analysis of the Active Ingredients from TongQiaoHuoXue Decoction Acting on the Neurocytes

“…[1][2][3][4] Our previous studies showed that TQHXD had an evident neuro protective effect. [5][6][7][8][9][10] In our previous experiment, fingerprints of Tongqiao Huoxue Decoction by HPLC had been done. 11) But the effective substance of TQHXD on neuroprotective effect still needs to be investigated.…”