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.