Hydroxysafflor yellow A exerts neuroprotective effects in cerebral ischemia reperfusion-injured mice by suppressing the innate immune TLR4-inducing pathway.

The innate immune response, which is tightly regulated by Toll-like receptor 4 (TLR4) pathway, has been shown to play a critical role in brain damage following cerebral ischemia-reperfusion injury. Hydroxysafflor yellow A (HSYA) is the active component extracted from the Flos Carthami and has been reported to decrease neurological deficit scores following ischemia-reperfusion injury. However, the precise mechanism by which it exerts these neuroprotective effects remains poorly understood. In this study, we demonstrated that the administration of HSYA could significantly down-regulate TLR4 expression in middle cerebral artery occlusion (MCAO) mice. Following the down-regulation of TLR4 by HSYA treatment, cerebral infarction and inflammatory neuronal damage was alleviated. The number of apoptotic neurons in the HSYA-treated group was significantly decreased along with the decrease in TLR4 expression in MCAO mice. Activation of the NF-κB and MAPK signaling pathways was observed at 1h following ischemia and at 24h post-reperfusion. HSYA could significantly inhibit NF-κB p-p65, ERE1/2, JNK and p38 phosphorylation, which coincided with the suppressed secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nitric oxide (NO). Moreover, brain-derived neurotrophic factor (BDNF) was up-regulated following 1h of ischemia and continued to increase initially during reperfusion but was down-regulated at later stages. Following treatment with HSYA, BDNF was up-regulated relative to control MCAO mice at 1h post-ischemia and at 12 and 24h post-reperfusion. Our data suggest that HSYA exerts neurotrophic and anti-inflammatory functions against ischemic stroke by inhibiting TLR4 pathway-mediated signaling responses.

Lv Y ，Qian Y ，Fu L ，Chen X ，Zhong H ，Wei X ... -  《-》

Hydroxysafflor Yellow A Attenuates Neuron Damage by Suppressing the Lipopolysaccharide-Induced TLR4 Pathway in Activated Microglial Cells.

Lv Y ，Qian Y ，Ou-Yang A ，Fu L ... -  《-》

Protective effect of hydroxysafflor yellow A alone or in combination with acetylglutamine on cerebral ischemia reperfusion injury in rat: A PET study using (18)F-fuorodeoxyglucose.

Hydroxysafflor yellow A (HSYA) and acetylglutamine (NAG) are extensively applied in the treatment of brain injury. In this study, we investigated the neuroprotective effect and underlying mechanism of HSYA alone or together with NAG using a rat model of cerebral ischemia reperfusion injury. Male Sprague-Dawley (SD) rats (n = 5) were intraperitoneally injected with 5, 10, 20 mg/kg HSYA, 300 mg/kg NAG and 10 mg/kg HSYA+300 mg/kg NAG after the onset of reperfusion and once each day for the following 7 days. After assessing the neurological deficit and infarct volume, we used 18F-FDG-PET to evaluate the regional cerebral metabolic rate of glucose consumption, immunohistochemical analysis to detect the expression of GFAP, NGF, Bcl-2, Bax, caspase-3 and ICAM-1 in brain tissue at day 7 after cerebral I/R injury. Meanwhile, the mRNA levels of ICAM-1, IL-1ß, TNF-α and NF-κB were determined by qRT-PCR, the protein levels of Bcl-2, Bax and caspase-3 were detected by western blot. The results indicated that HSYA significantly up-regulated glucose metabolism, improved neurological function, decreased cerebral infarction volume. HSYA alone or together with NAG attenuated apoptosis and inflammation by up-regulating GFAP, NGF and Bcl-2 expression, suppressing the expression of Bax, caspase-3 and ICAM-1, IL-1ß, TNF-α and NF-κB. These finding suggested that HSYA exerted neuroprotection against cerebral I/R injury by modulating inflammation and apoptosis process, and HSYA in combination with NAG possessed a synergetic effect on protecting cerebral I/R brain injury.

Deng L ，Wan H ，Zhou H ，Yu L ，He Y ... -  《-》

Hydroxysafflor yellow A ameliorates lipopolysaccharide-induced acute lung injury in mice via modulating toll-like receptor 4 signaling pathways.

Liu YL ，Liu YJ ，Liu Y ，Li XS ，Liu SH ，Pan YG ，Zhang J ，Liu Q ，Hao YY ... -  《-》

Hydroxysafflor yellow A alleviates myocardial ischemia/reperfusion in hyperlipidemic animals through the suppression of TLR4 signaling.

Han D ，Wei J ，Zhang R ，Ma W ，Shen C ，Feng Y ，Xia N ，Xu D ，Cai D ，Li Y ，Fang W ... -  《Scientific Reports》