Hydroxysafflor yellow A (HSYA) and
anhydrosafflor yellow B (AHSYB) are the main water-soluble compounds in Carthamus tinctorius L. However, studies on the effect of AHSYB on
cerebral ischemia/reperfusion (I/R) injury and the
therapeutic effect of HSYA by regulating silent information regulator 1 (
SIRT1) pathway remain obscure. In this study, we investigated whether the
neuroprotective effects of HSYA and AHSYB on
oxygen-
glucose deprivation/reoxygenation in primary-cultured hippocampal neuronal cells and the
middle cerebral artery occlusion and reperfusion model in rats are associated with the regulation of the
SIRT1 pathway. In vitro, HSYA and AHSYB increased cell viability, depressed oxidation properties, and reduced neuronal cell apoptosis. In vivo results showed that HSYA and AHSYB effectively reduced
infarct volume, improved neurological function, suppressed apoptosis, and decreased the oxidative stress reaction. Besides, RT-PCR and Western blot analysis showed that HSYA and AHSYB increased the
mRNA and
protein expressions of the main factors in the
SIRT1 pathway, including
SIRT1, forkhead box O (FOXO) 1, and
peroxisome proliferator-activated receptor coactivator 1α (PGC1α), decreased the expression of Bax, and increased the expression of Bcl-2. The results from immunohistochemistry also showed that the expressions of
SIRT1, FOXO1, and PGC1α were increased
after treatment with HSYA and AHSYB. Furthermore, the
neuroprotective effects of HSYA and AHSYB were abolished by EX527 (SIRT1-specific inhibitor). These results indicated that HSYA and AHSYB should be developed into potential drugs for treating cerebral I/R injury via the
SIRT1 pathway. Although HSYA and AHSYB have different chemical structures, both of them exert similar neuroprotective properties against I/R injury in vitro and in vivo, which means that AHSYB is also a non-negligible component in safflower.