2. Academic Validation
  3. Activation of Nrf2 by Ginsenoside Rh3 protects retinal pigment epithelium cells and retinal ganglion cells from UV

Activation of Nrf2 by Ginsenoside Rh3 protects retinal pigment epithelium cells and retinal ganglion cells from UV

  • Free Radic Biol Med. 2018 Mar;117:238-246. doi: 10.1016/j.freeradbiomed.2018.02.001.
Chun-Zhou Tang 1,  Ke-Ran Li 2,  Qing Yu 2,  Qin Jiang 3,  Jin Yao 4,  Cong Cao 5
Affiliations

Affiliations

  • 1 The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China; Ophthalmology Department, Jiangsu Jiangyin people's Hospital, Jiangyin, China.
  • 2 The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China.
  • 3 The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
  • 4 The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
  • 5 The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China; Center of Translational Medicine, The First People Hospital of Zhangjiagang City, Soochow University, Suzhou, China; North District, The Municipal Hospital of Suzhou, Suzhou, China. Electronic address: [email protected].
PMID: 29427790 DOI: 10.1016/j.freeradbiomed.2018.02.001
Abstract

Excessive Ultra-violet (UV) radiation shall induce damages to resident retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs). Here we tested the potential activity of Ginsenoside Rh3 ("Rh3") against the process. In cultured human RPEs and RGCs, pretreatment with Rh3 inhibited UV-induced Reactive Oxygen Species (ROS) production and following apoptotic/non-apoptotic cell death. Rh3 treatment in retinal cells induced nuclear-factor-E2-related factor 2 (Nrf2) activation, which was evidenced by Nrf2 protein stabilization and its nuclear translocation, along with transcription of antioxidant responsive element (ARE)-dependent genes (HO1, NOQ1 and GCLC). Nrf2 knockdown by targeted-shRNA almost abolished Rh3-induced retinal cell protection against UV. Further studies found that Rh3 induced microRNA-141 ("miR-141") expression, causing downregulation of its targeted gene Keap1 in RPEs and RGCs. On the other hand, Rh3-induced Nrf2 activation and retinal cell protection were largely attenuated by the miR-141's inhibitor, antagomiR-141. In vivo, intravitreal injection of Rh3 inhibited retinal dysfunction by LIGHT damage in mice. Rh3 intravitreal injection also induced miR-141 expression, Keap1 downregulation and Nrf2 activation in mouse retinas. We conclude that Rh3 protects retinal cells from UV via activating Nrf2 signaling.

Keywords

Ginsenoside Rh3; MicroRNA-141; Nrf2, UV radiation; Oxidative stress; Retinal cells.

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