Tanshinone IIA and hydroxy safflower yellow A reduce cerebral injury via TLR4/NF-κB pathway in rats

Cerebral ischemia-reperfusion injury (CIRI) is a cerebrovascular disorder with high rates of incidence, disability, and death. It has been identified that Salvia miltiorrhiza and safflower have a protective effect in CIRI. However, the mechanisms of which remain to be elucidated. In this study, we investigated the protective mechanisms of the components of Salvia miltiorrhiza and safflower in CIRI, based on the TLR4/NF-κB signaling pathway. Sprague Dawley (SD) rats were used to establish the rat middle cerebral artery occlusion/reperfusion (MACO/R) model by the suture method. Drugs were injected intraperitoneally at 0 and 2 h, followed by once-daily treatment for 3 days. Neurological function and the volume of brain infarction were evaluated, and the pathological changes in brain tissue were examined using HE staining. ELISA kits were used to detect the concentrations of TNF-α and IL-6, while RT-qPCR, Western blot, and immunofluorescence were employed to evaluate the mRNA and protein expression in brain tissue. Following a combination of tanshinone IIA and hydroxy safflower yellow A treatment, our findings indicated that cerebral infarct volume and neurological deficits were reduced. The findings of HE staining revealed an improvement in cerebral histopathological damage in rats with MCAO/R. The levels of TNF-α and IL-6 in serum, as well as the expression of TLR4 and NF-κB in rat brains, were significantly reduced (P < 0.0001). Taken together, these results indicate that the combination of tanshinone ⅡA and hydroxyl safflower yellow A may exhibit a neuroprotective effect on cerebral I/R injury in rats by activating the TLR4/NF-κB signaling pathway.