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Oncotarget. 2017 Dec 15;8(70):115434-115443. doi: 10.18632/oncotarget.23272. eCollection 2017 Dec 29.

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

Xu H#1, Liu W#1, Liu T#1, Su N2, Guo C1, Feng X1, Dou F1, Ding Y1,3, Shi L3, Wen A1.

Author information

1
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
2
Department of Radiation Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
3
Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
#
Contributed equally

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.

KEYWORDS:

Danshensu; hydroxysafflor yellow A; ischemic stroke; neuroprotective effect; synergistic effect

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that they have no competing interests.

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