Extracts of Carthamus tinctorius L. contain yellow and red pigments including hydroxysafflor yellow A (HSYA), safflor yellow B, safflomin A, safflomin C, as well as other chemicals. Among all these components, HSYA has been demonstrated as the most active chemicals. In 2003, Zhu et al. [19] first reported the neuroprotective effects of HSYA on cerebral ischemic injury in both in vivo and in vitro studies. Considering that oxidative stress is an important cause of tissue damage after I/R injury, Jin et al. [7] examined the possible antioxidative effect of HSYA and demonstrated that HSYA could scavenge hydroxyl radicals and inhibit lipid peroxidation in vitro. The antioxidative effect of HSYA, as proposed by Jin et al., may be attributed to its multiple phenolic hydroxyl groups. In accordance with Jin’s study, Tian et al. [20,21] further demonstrated that HSYA protected the cortex mitochondrial against I/R injuries through scavenging of free radicals, reduction of lipid peroxidation, inhibition of Ca2+ overload, and inhibition of the opening of mitochondrial permeability transition pores (mtPTP). Later, Wei’s study of focal cerebral ischemia reperfusion injury showed that, compared with animals that received no pharmacological treatment, animals treated with HSYA revealed reduced MDA content, increased SOD activity and total antioxidative capability in the brain and serum [9]. This study provided direct in vivo evidence that HSYA confers neuroprotection through its antioxidative action. Moreover, as reported by Zhu [22] and Ye [23], the neuroprotective effect of HSYA might also beattributed to its inhibition of thrombosis formation and platelet aggregation, its regulation on PGI2/TXA2 (prostaglandin I2/thromboxane A2) ratio and blood rheological changes, as well as its suppression of inflammatory responses. Although beneficial effects of HSYA have been demonstrated in I/R injuries of various organs, its effect on spinal cord I/R injuries has not been studied yet. Thus, we conducted the present study to investigate the possible neuroprotective effect of HSYA against spinal cord I/R injuries in rabbits. The dose of 10 mg/kg was chosen based on our prior preliminary study and related references which demonstrated remarkable protection of HSYA against brain I/R injury at the dose of 8 mg/kg in rats [9]. The hypothesis that HSYA could protect against spinal cord I/R injury was accepted because neurological evaluation after reperfusion revealed improved motor function of hinder limbs in animals that received HSYA treatment. However, neurological scores of animals in HSYA group were still PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27864321 lower than that of sham group, suggesting that HSYA alone may not be effective enough to completely restore motor functions. The beneficial effect of HSYA was also confirmed by CI-1011 custom synthesis histopathological study. While severe vacuolization of gray matter and degeneration of motor neurons were observed in the non-treated group, only mild tissue destruction with significant more normal motor neurons were detected in the HSYA-treated group. To further answer the question of whether the protective effect of HSYA was related to its antioxidative efficiency, we performed the biochemical analysis to study the changes in MDA level and SOD activity in spinal cords. Lipid peroxidation induced by ROS is a primary cause of reperfusion injury in spinal cords when blood flow is restored, and the level of MDA, a relatively stable end product of lipid peroxidation, is considered as indi.