Hydroxysafflor yellow A acutely attenuates blood-brain barrier permeability, oxidative stress, inflammation and apoptosis in traumatic brain injury in rats1

Abstract

To investigate the therapeutic benefits of Hydroxysafflor yellow A (HSYA) on blood-brain barrier (BBB) vulnerability after traumatic brain injury (TBI) and identify its potential action of mechanisms on TBIinduced injuries. Methods: The rat TBI model was performed by using a controlled cortical impact device. The BBB permeability induced by TBI was measured through Evans Blue dye superflux and western blotting or polymerase chain reaction (PCR) for tight junctional proteins (TJPs). The post-TBI changes in oxidative stress markers, inflammatory response and neuron apoptosis in brain tissue were also tested. Results: Herein, the results showed that HSYA acutely attenuated BBB permeability via increasing the production of the TJPs, including occludin, claudin-1 and zonula occludens protein 24 h after TBI. Additionally, HSYA could suppress the secretion of proinflammatory factors, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α (IL-1β, IL-6, and TNF-α), and also concurrently down-regulate the expression of inflammation-related Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-kB) protein. These HSYA challenged changes were accompanied by the decreased TBI induced oxidative stress markers and inhibited the expression of apoptosis proteins Bax, caspase-3 and caspase-9. Conclusions: Taken together, all findings suggested that HSYA (30 mg/kg) are against TBI through improving the integrity in BBB, which are associated with the antioxidant, anti-inflammation and antiapoptosis via the probable mechanism of down-regulation of the TLR4/NF-kB pathway, and its in-detail protective mechanisms are under study.

Hydroxysafflor yellow A attenuates oxidative stress injury‑induced apoptosis in the nucleus pulposus cell line and regulates extracellular matrix balance via CA XII

“…For example, HSYA reduced oxidative stress and reversed the increase in Bax and caspase-3 from nephropathy in type 2 diabetic rats, and significantly increased the protein expression of Bcl-2 in renal tissue ( 15 ). In addition, in traumatic brain injury in rats, HSYA protected neural cells against oxidative stress and anti-apoptosis by inhibiting the protein expression level of Bax, caspase-3, and caspase-9, while increasing antioxidant enzyme concentrations ( 14 ). All of the aforementioned studies confirmed that HSYA has an essential role in anti-oxidative stress and anti-apoptosis.…”

“…It is a type of traditional Chinese medicine that promotes blood circulation and provides pain relief. Hydroxysafflor yellow A (HSYA), a mono chalcone glycoside derived from safflower, is the main component of safflower yellow pigment ( 14 ). Lee et al ( 15 ) found that HSYA could protect the kidney by inhibiting oxidative stress injury and renal cell apoptosis induced by nephropathy in type 2 diabetic rats.…”

“…Lee et al ( 15 ) found that HSYA could protect the kidney by inhibiting oxidative stress injury and renal cell apoptosis induced by nephropathy in type 2 diabetic rats. In addition, HSYA could protect neuronal cells from cellular damage induced by oxidative stress in rats with traumatic brain injury ( 14 ). Furthermore, HSYA also plays a role in the regulation of ECM balance.…”

Pharmacological Actions, Molecular Mechanisms, Pharmacokinetic Progressions, and Clinical Applications of Hydroxysafflor Yellow A in Antidiabetic Research

“…The role of NF-κB signal in the antidiabetic activities of HSYA has not been previously reported. Figure 2 indicates that NF-κB signal plays an important role in the use of HSYA to treat other inflammatory diseases [29][30][31][32][33][34][35][36][37][38]. This might provide some research points to explore antiinflammatory mechanisms of HSYA in the treatment of diabetes and diabetes complications.…”

“…Possible Anti-Inflammatory Mechanisms in Antidiabetic Research of HSYA. In Figure2, organ damages treated by HSYA via the NF-κB pathway include brain damages such as ischemia reperfusion-injury, traumatic brain injury, ischemic stroke, and Alzheimer's disease (AD)[29][30][31][32]; lung injury such as fetal lung fibroblasts, chronic obstructive pulmonary disease, and acute respiratory distress syndrome…”