Synergistic neuroprotective effects of Danshensu and hydroxysafflor yellow A on cerebral ischemia-reperfusion injury in rats.

Hang Xu,Chao Guo,Tianlong Liu,Yi Ding,Aidong Wen,Wenxing Liu,Ning Su,Fang Dou,Lei Shi,Xiaona Feng

doi:10.18632/oncotarget.23272

Abstract

Ischemic stroke is a common cerebrovascular disease with substantial morbidity and mortality worldwide. However, therapeutic options to minimize the cerebral ischemia-reperfusion (I/R) injury are limited. In China, combination of herb Danshen (Salvia miltiorrhiza Bge) and Honghua (Carthamus tinctorius L.) is effective for stroke treatment in patients but its underlying mechanism requires further investigation. Our study was conducted to evaluate and explore the synergistic effects of two herb ingredients Danshensu and hydroxysafflor yellow A (HSYA) on cerebral ischemia-reperfusion (I/R) injury in rats. Rats were randomly assigned to the following five groups: sham group, model group, Danshensu group, HSYA group, and Danshensu+HSYA group. Under our experimental conditions in vitro, oxygen-glucose deprivation (OGD) model was established to determine the synergistic neuroprotective effects of Danshensu and HSYA. With such methods as neurological deficits scoring, TTC, HE and TUNEL staining, and ELISA detection, the results demonstrated that administration of either Danshensu or HSYA improved neurological defects and alleviated pro-inflammatory and oxidative stress reactions. Notably, combination of Danshensu and HSYA exerted more effective results than that used alone. Furthermore, western blot analysis results showed that Danshensu and HSYA combination displayed synergistic regulation on TLR4/NF-κB and Nrf2/HO-1 pathways. Consistently, Danshensu +HSYA group exhibits better neuroprotection in primary neurons with OGD model compared with Danshensu or HSYA group. Taken together, we found for the first time that Danshensu plus HSYA could achieve remarkable synergistic neuroprotective effects on I/R injury, which is related to the anti-inflammatory and antioxidant pathways.

Highlights

Stroke is one of common lethal cerebrovascular diseases with substantial morbidity and mortality around the world [1]
Combined with the important role of Inflammation and oxidative stress in stroke, we hypothesized that the combined use of Danshensu and hydroxysafflor yellow A (HSYA) may significantly increase the therapeutic effect on stroke through Toll-like receptor 4 (TLR4)/ nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways
Both the neurological deficit examination and infarct volume by triphenyltetrazolium chloride (TTC) staining demonstrated that Danshensu and HSYA in combination synergistically protected neurological deficit and reduced infarction volume after stroke

Summary

Introduction

Stroke is one of common lethal cerebrovascular diseases with substantial morbidity and mortality around the world [1]. In efforts to find drugs to effectively prevent and treat stroke, more and more attention has been focused on the chemicals extracted from traditional Chinese herbs [2]. In traditional Chinese medicine (TCM), a number of herbs are paired together in order to enhance the therapeutic effects. Danshen (Salvia miltiorrhiza Bge) and Honghua (Carthamus tinctorius L.) are valued Chinese traditional herbs for the treatment of cardiovascular diseases by multiple pharmacology effects such as anti-inflammatory and antioxidant role [5, 6]. Danshen and Honghua combination (such as DanHong injection, a Chinese material standardized clinical product) has been widely employed for cerebrovascular patients [5, 6]

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Results

Conclusion