Lignans Extracted from Eucommia Ulmoides Oliv. Protects Against AGEs-Induced Retinal Endothelial Cell Injury

Background/Aims: Advanced glycation end products (AGEs) could elicit oxidative stress, trigger and aggravate endothelium damage in several ischemic retinopathies including diabetic retinopathy (DR). The leaves of Eucommia ulmoides O., also referred to as Tu-chung or Du-zhong, have been used for the treatment of hypertension and diabetes, showing great antioxidant activity and anti-glycation activity. Lignans is one of the main bioactive components of Eucommia ulmoides. This study mainly investigated the effect of lignans treatment on AGEs-induced endothelium damage. Methods: MTT assay, Hoechst staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of lignans treatment on endothelial cell function in vitro. Retinal trypsin digestion, Evans blue assay, isolectin staining, and western blots were conducted to determine the effect of lignans treatment on retinal microvascular function in vivo. Western blot, protein immunoprecipitation (IP), MTT assays, and enzyme activity assay was conducted to detect the effect of ligans treatment on oxidative stress response. Results: Lignans protected retinal endothelial cell against AGEs-induced injury in vitro and diabetes-induced vascular dysfunction in vivo. Lignans treatment could regulate oxidative stress response in retinal endothelial cell line, retina, and liver. Moreover, we showed that NRF2/HO-1 signaling was critical for lignans-mediated oxidative stress regulation. Conclusion: Lignans treatment could protect against endothelial dysfunction in vivo and in vitro via regulating Nrf2/HO-1 signaling. Lignans might be developed as a promising drug for the treatment of diabetes-induced microvascular dysfunction.