Abstract
High-mobility group box-1 (HMGB1) is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE) on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day) was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE) and the activity of nuclear factor-kappa B (NF-κB) in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes.
Highlights
Diabetic retinopathy (DR) causes adult vision loss and blindness and is among the principal microvascular complications in diabetic patients
These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting High-mobility group box-1 (HMGB1)-receptor for advanced glycation end products (RAGE)-NF-κB activation in diabetic retinas
We found that while HMGB1 was expressed at low levels in the ganglion cell layer of a normal retina, HMGB1 was highly expressed in the nuclei and levels in the ganglion cell layer of a normal retina, HMGB1 was highly expressed in the nuclei and diffusely expressed in the cytoplasm in the diabetic retinas, and HMGB1 expression in the retina was diffusely expressed in the cytoplasm in the diabetic retinas, and HMGB1 expression in the retina primarily localized within ganglion cells and the inner nuclear layer (Figure 2A)
Summary
Diabetic retinopathy (DR) causes adult vision loss and blindness and is among the principal microvascular complications in diabetic patients. Strong evidence suggests that continuous low-grade inflammation is primarily involved in the pathogenesis of diabetic retinopathy [1]. High-mobility group box-1 (HMGB1) is involved in the pathogenesis of diabetic microvascular complications, plays an important role in the inflammatory response, and its pro-angiogenic processes are closely associated with diabetic retinopathy [2]. HMGB1 is an architectural chromatin-binding nuclear protein that has been implicated as a mediator of both non-infectious and infectious inflammatory diseases [3]. Necrotic cell death can result in the passive leakage of HMGB1 from cells when the protein is no longer bound to DNA, which induces an inflammatory response and promotes tissue repair and angiogenesis [4].
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