Tetramethylpyrazine Protects Retinal Capillary Endothelial Cells (TR-iBRB2) against IL-1β-Induced Nitrative/Oxidative Stress

Abstract

Blood-retinal barrier (BRB) breakdown is one of the primary causes of diabetic retinopathy (DR). The pro-inflammatory factor interleukin-1β (IL-1β) was reported to be involved in the induction of BRB breakdown during the pathogenesis of DR. In the present study, we investigated the protective effect of tetramethylpyrazine (TMP), a major active component of the traditional herb Ligusticum chuanxiong, on IL-1β-induced cell death of the rat retinal capillary endothelial TR-iBRB2 cells. Our results showed that IL-1β-induced cell dysfunction in TR-iBRB2 cells via inducing nitrative/oxidative stress; however, such effect was attenuated with the pre-treatment of TMP. The cellular protective effect of TMP was likely to be mediated through the inhibition of inducible nitric oxide synthase (iNOS) expression and leukostasis as well as suppression of reactive oxygen species (ROS) generation, mitochondrial dysfunction and MAPKs activation. These findings significantly contribute to a better understanding of the protective effect of TMP in DR and form the basis of the therapeutic development of TMP in treating such disease in the future.

Antioxidant and Anti‐Inflammatory Effects of Blueberry Anthocyanins on High Glucose‐Induced Human Retinal Capillary Endothelial Cells

“…The upregulated reactive oxygen species (ROS) generation inferred the potent stimuli for the oxidative stress [ 21 ]. In this study, BAE, Mv, Mv-3-glc, and Mv-3-gal attenuated high glucose-induced oxidative stress in HRECE by reducing ROS levels.…”

“…Other isoforms, such as neuronal NOS (nNOS) and inducible NOS (iNOS), should also be effective. Retinal capillary endothelial cells can express iNOS when stimulated by inflammatory mediators, such as IL-1 β [ 21 ]. Moreover, nitrosative/oxidative stress might be related to NO levels.…”

Tetramethylpyrazine (TMP) protects rats against acute pancreatitis through NF-κB pathway

“…However, the exact mechanism underlying the effect of TMP in AP has not been completely addressed. Multiple studies have shown that TMP inhibits NF-kB activity, thereby causing inhibition of inflammatory factor release and protecting cells from damage [17][18][19]. In addition, TMP significantly induced apoptosis and G0/G1 arrest in osteosarcoma cells by downregulating the protein expression of nuclear NF-κB p65(P65), bcl-2 and cyclin D1 [20].…”

ESE1 is Associated with Neuronal Apoptosis in Lipopolysaccharide Induced Neuroinflammation

“…Co-transfection of ESE-1 with p50 and p65 subunits of NF-kB not only synergistically enhances ESE-1 transactivation of inducible form of nitricoxide synthase (iNOS) promoter but also controls dendritic cell driven T cells differentiation through attribution to impairment of IL-6 production in response to inflammation. Lipopolysaccharide (LPS), a component of outer cell wall of gram-negative bacteria [24], can lead to cell inflammation and apoptosis [25,26]. LPS induces the activation of pro-inflammatory cytokines, and other signaling pathways that ultimately lead to apoptosis and cell death.…”