Affiliation:
1. Department of Ophthalmology Xi'an Hospital of Traditional Chinese Medicine Xi'an Shaanxi Province P.R. China
2. Shaanxi University of Traditional Chinese Medicine Xianyang Shaanxi Province P.R. China
3. Department of Ophthalmology Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine Xianyang Shaanxi Province P.R. China
4. Department of Ophthalmology Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University Xi'an Shaanxi Province P.R. China
Abstract
AbstractDiabetic retinopathy (DR) is one of the most frequently occurring diabetic complications associated with inflammation and oxidative stress. Platycodin D (PLD) is a bio‐active saponin that has been reported to exhibit anti‐inflammation, anti‐oxidative, and antidiabetic activities. Therefore, we speculated the protective effects of PLD on DR in the present study. Our results demonstrated that PLD attenuated high glucose (HG)‐induced inflammation, as evidenced by decreased production of TNF‐α, IL‐1β, IL‐6. The HG‐induced oxidative stress was prevented by PLD with decreased ROS production and malondialdehyde (MDA) level, as well as increased activities of superoxide dismutase and glutathione (GSH). In addition, treatment of PLD significantly decreased the apoptotic rate in HG‐induced ARPE‐19 cells. The HG‐caused increases in expression of bax and cleaved capsase‐3, as well a decrease in bcl‐2 expression were attenuated by PLD. Furthermore, PLD suppressed the activation of TLR4/MyD88/NF‐κB and enhanced the activation of Nrf2/HO‐1 pathway in HG‐induced ARPE‐19 cells. Additionally, overexpression of TLR4 attenuated the anti‐inflammatory, while knockdown of Nrf2 reversed the anti‐oxidative and anti‐apoptotic activities of PLD in HG‐stimulated ARPE‐19 cells. Furthermore, PLD attenuates retinal damage in DR rats. Finally, we demonstrated that PLD weakened the TLR4/MyD88/NF‐κB p65 pathway and promoted the Nrf2/HO‐1 pathway in vivo. Taken together, these findings indicated that PLD exerted protective effects against DR, which were attributed to the regulation of TLR4/MyD88/NF‐κB and Nrf2/HO‐1 signaling pathways.
Subject
Molecular Medicine,Biochemistry,Drug Discovery,Pharmacology,Organic Chemistry