Protective effect of puerarin on diabetic retinopathy in rats.

Ophthalmology Hospital, The First Clinical College of Harbin Medical University, Harbin, People's Republic of China.
Molecular Biology Reports (Impact Factor: 2.51). 07/2008; 36(5):1129-33. DOI: 10.1007/s11033-008-9288-2
Source: PubMed

ABSTRACT Puerarin is a major active ingredient extracted from the traditional Chinese medicine Ge-gen. The purpose of this study is to investigate the protective effect of puerarin on diabetic retinopathy (DR) and its mechanisms in rats. Seventy-two male Wistar rats were selected and divided at random into three main groups: control group, streptozotocin (STZ) group and puerarin + STZ group. Retinal histopathological observation and electron microscopic examination were performed; retinal vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 (HIF-1alpha) gene expressions were examined by Reverse transcription-polymerase chain reaction (RT-PCR) analysis. Results showed that the DR induced by STZ was significantly reduced by the treatment of puerarin as judged by the reduction of morphological changes of inner nuclear layer and outer nuclear layer at any time-point. Puerarin regulates expressions of VEGF and HIF-1alpha stimulated by STZ. It was concluded that puerarin exerts significant protective effects against DR in rats, likely regulating angiogenesis factors expressions, and thus may be an effective and promising medicine for treatment of DR.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Significance: In this review, we have discussed the efficacy and effect of small-molecules that act as prolylhydroxylase inhibitors (PHDIs). The use of these compounds causes upregulation of the pro-angiogenic factors and hypoxia inducible factor-1α and 2α (HIF-1α and HIF-2α) to enhance angiogenic, glycolytic, erythropoietic and anti-apoptotic pathways in the treatment of various ischemic diseases responsible for significant morbidity and mortality in humans. Recent Advances: Sprouting of new blood vessels from the existing vasculature and surgical intervention, such as coronary bypass and stent insertion, have been shown to be effective in attenuating ischemia. However, the initial reentry of oxygen leads to the formation of reactive oxygen species (ROS) that cause oxidative stress and result in ischemia/reperfusion (IR) injury. This apparent "oxygen paradox" must be resolved to combat IR injury. During hypoxia, decreased activity of PHDs initiates the accumulation and activation of HIF-1α, wherein the modulation of both PHD and HIF-1α appear as promising therapeutic targets for the pharmacological treatment of ischemic diseases. Critical Issues: Research on PHDs and HIFs has shown that these molecules can serve as therapeutic targets for the ischemic diseases by modulating glycolysis, erythropoiesis, apoptosis and angiogenesis. Efforts are underway to identify and synthesize safer small-molecule inhibitors of PHDs that can be administered in vivo as therapy against the ischemic diseases. Future Directions: This review presents a comprehensive and current account of the existing small-molecule PHDIs and their use in the treatment of ischemic diseases with a focus on the molecular mechanisms of therapeutic action in animal models.
    Antioxidants & Redox Signaling 09/2013; · 8.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In diabetic retinopathy (DR), visual deterioration is related with retinal neovascularization and vascular hyperpermeability. Anti-vascular endothelial growth factor (VEGF) agents are currently utilized to suppress retinal neovascularization and macular edema (ME); however, there are still concerns on the widespread use of them because VEGF is a trophic factor for neuronal and endothelial cells in the retina. As an alternative treatment strategy for DR, it is logical to address hypoxia-related molecules to treat DR because the retina is in relative hypoxia as DR progresses. In this study, we demonstrate that destabilization of hypoxia-inducible factor-1α (HIF-1α) by SH-1242 and SH-1280, novel heat shock protein 90 (hsp90) inhibitors, leads to suppression of hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retina. In vitro experiments showed that these inhibitors inhibited hypoxia-induced upregulation of target genes of HIF-1α and further secretion of VEGF. Furthermore, these inhibitors effectively suppressed expression of target genes of HIF-1α including vegfa in the retina of oxygen-induced retinopathy (OIR) mice. Interestingly, despite hsp90 inhibition, these inhibitors do not induce definite toxicity at the level of gene expression, cellular viability, and histologic integrity. We suggest that SH-1242 and SH-1280 can be utilized in the treatment of DR, as an alternative treatment of direct VEGF inhibition.
    Journal of molecular medicine (Berlin, Germany). 05/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.
    BioMed Research International 07/2014; 2014. · 2.88 Impact Factor